ElsevierActa Medica Okayama0032-579110432025An ultra-simplified protocol for PCR template preparation from both unsporulated and sporulated Eimeria oocysts104810ENArutoTakanoDepartments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan UniversityDennis V. UmaliDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, CollegeApril H. WardhanaResearch Center for Veterinary Science, National Research and Innovation AgencyDyah H. SawitriResearch Center for Veterinary Science, National Research and Innovation AgencyIsaoTeramotoDepartments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan UniversityToshimitsuHatabuLaboratory of Animal Physiology, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYasutoshiKidoDepartments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan UniversityAkiraKanekoDepartments of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan UniversityKazumiSasaiDepartments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan UniversityHiromitsuKatohDepartments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan UniversityMakotoMatsubayashiDepartments of Veterinary Immunology, Graduate School of Veterinary Medical Sciences, Osaka Metropolitan UniversityMolecular biological techniques have enabled the accurate identification of the avian Eimeria parasite, however, the preparation of PCR template remains a bottleneck due to contaminants from feces and the robust oocyst's wall resistant to chemical and mechanical force. Generally, the preparation of PCR template involves three main steps: (1) pretreatment of oocysts; (2) disruption of oocysts; and (3) purification of genomic DNA. We prepared PCR templates from both unsporulated and sporulated E. tenella oocysts using various protocols, followed by species-specific PCR to define the limit of detection. Our data revealed that whereas neither pretreatment of oocysts with sodium hypochlorite nor purification of genomic DNA with commercial kits improved the limit of detection of PCR, disruption of oocysts was a critical step in the preparation of PCR templates. The most sensitive PCR assay was achieved with the template prepared by disrupting oocysts suspended in distilled water, followed by bead-beating and heating at 99°C for 5 min, which detected 0.16 oocysts per PCR. This ultra-simplified protocol for preparation of PCR template, which does not require expensive reagents or equipment, will significantly enhance the sensitive and efficient molecular identification of Eimeria. It will improve our understanding of the prevalence of this parasite at the species level and contribute to the development of techniques for the control in the field.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2772-963X452025Prognostic Value of Pericoronary Fat Attenuation Index on Computed Tomography for Hospitalization for Heart Failure101685ENMitsutakaNakashimaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroNishiharaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShoheiHaraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medicine CentreShinsukeYuasaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBACKGROUND Pericoronary fat attenuation index (FAI) assessed on computed tomography is associated with the inflammation of the pericoronary artery. <br>
OBJECTIVES This study aimed to investigate whether pericoronary FAI predicts hospitalization for heart failure with preserved ejection fraction (HFpEF). <br>
METHODS This retrospective single-center study included 1,196 consecutive patients who underwent clinically indicated coronary computed tomography angiography (CCTA) and transthoracic echocardiography. We assessed the FAI of proximal 40-mm segments for each major epicardial coronary vessel. The primary outcome was the incidence of hospitalization for HFpEF. Patients were divided into groups based on the optimal cutoff value for predicting hospitalization for HFpEF by receiver operating characteristic curve analysis. <br>
RESULTS During a median follow-up of 4.3 years, 29 hospitalizations for HFpEF occurred. Multivariable Cox regression analysis revealed that a left anterior descending artery (LAD)-FAI >=-63.4 HU and a left circumflex artery-FAI >=-61.6 HU were significantly associated with hospitalization for HF after adjustment for age and sex (HR: 4.8; 95% CI: 2.1-10.8 and HR: 4.5; 95% CI: 2.1-9.4, respectively). The addition of LAD-FAI >-63.4 HU to a model incorporating other risk factors, including hypertension, estimated glomerular filtration rate <60 mL/min/1.73 m2, and significant stenosis on CCTA, increased the C-statistic for predicting hospitalization for HFpEF from 0.646 to 0.750 (P = 0.010). <br>
CONCLUSIONS LAD-and left circumflex artery-FAI can predict hospitalization for HFpEF in patients undergoing clinically indicated CCTA. Pericoronary inflammation may be useful for identifying patients at high risk of developing HFpEF. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-01022142025The Medaka approach to evolutionary social neuroscience3241ENSatoshiAnsaiUshimado Marine Institute, Okayama UniversityTowakoHiraki-KajiyamaGraduate School of Life Sciences, Tohoku UniversityRyutaroUedaGraduate School of Life Sciences, Tohoku UniversityTakahideSekiGraduate School of Life Sciences, Tohoku UniversitySaoriYokoiSchool of Pharmaceutical Sciences, Hokkaido UniversityTakafumiKatsumuraSchool of Medicine, Kitasato UniversityHideakiTakeuchiGraduate School of Life Sciences, Tohoku UniversityPreviously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1880-65467522025Changes in adrenoceptor expression level contribute to the cellular plasticity of glioblastoma cells100016ENYutaroAsakaDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshioMasumotoDivision of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori UniversityAtsuhitoUnedaDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesVanessa D.ChinUMass Chan Medical School, UMass Memorial Medical CenterYusukeOtaniDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolTirsoPenaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolHaruyoshiKatayamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakutoItanoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTeruhikoAndoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRongshengHuangDepartment of Trauma Orthopedics, The Second Hospital of Dalian Medical UniversityAtsushiFujimuraDepartment of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesGlioblastoma cells are known to regulate their cellular plasticity in response to their surrounding microenvironment, but it is not fully understood what factors contribute to the cells' changing plasticity. Here, we found that glioblastoma cells alter the expression level of adrenoreceptors depending on their differentiation stage. Catecholamines are abundant in the central nervous system, and we found that noradrenaline, in particular, enhances the stemness of glioblastoma cells and promotes the dedifferentiation potential of already differentiated glioblastoma cells. Antagonist and RNAi experiments revealed that signaling through alpha 1D-adrenoreceptor is important for noradrenaline action on glioblastoma cells. We also found that high alpha 1Dadrenoreceptor expression was associated with poor prognosis in patients with gliomas. These data suggest that glioblastoma cells increase the expression level of their own adrenoreceptors to alter the surrounding tumor microenvironment favorably for survival. We believe that our findings will contribute to the development of new therapeutic strategies for glioblastoma.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X30142025Roles of basic amino acid residues in substrate binding and transport of the light-driven anion pump Synechocystis halorhodopsin (SyHR)108334ENMasakiNakamaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyasuNojiDepartment of Applied Chemistry, The University of TokyoKeiichiKojimaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySusumuYoshizawaAtmosphere and Ocean Research Institute, The University of TokyoHiroshiIshikitaDepartment of Applied Chemistry, The University of TokyoYukiSudoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMicrobial rhodopsins are photoreceptive seventransmembrane a-helical proteins, many of which function as ion transporters, primarily for small monovalent ions such as Na+, K+, Cl-, Br-, and I-. Synechocystis halorhodopsin (SyHR), identified from the cyanobacterium Synechocystis sp. PCC 7509, uniquely transports the polyatomic divalent SO42- inward, in addition to monovalent anions (Cl- and Br-). In this study, we conducted alanine-scanning mutagenesis on twelve basic amino acid residues to investigate the anion transport mechanism of SyHR. We quantitatively evaluated the Cl-and SO42- transport activities of the WT SyHR and its mutants. The results showed a strong correlation between the Cl-and SO42- transport activities among them (R = 0.94), suggesting a shared pathway for both anions. Notably, the R71A mutation selectively abolished SO42- transport activity while maintaining Cl- transport, whereas the H167A mutation significantly impaired both Cl-and SO42- transport. Furthermore, spectroscopic analysis revealed that the R71A mutant lost its ability to bind SO42- due to the absence of a positive charge, while the H167A mutant failed to accumulate the O intermediate during the photoreaction cycle (photocycle) due to reduced hydrophilicity. Additionally, computational analysis revealed the SO42- binding modes and clarified the roles of residues involved in its binding around the retinal chromophore. Based on these findings and previous structural information, we propose that the positive charge and hydrophilicity of Arg71 and His167 are crucial for the formation of the characteristic initial and transient anion-binding site of SyHR, enabling its unique ability to bind and transport both Cl-and SO42-.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1756-46461252025Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways106672ENSakiOkamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySayaKakimaruGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMayukoKoreishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMikaSakamotoNational Institute of Genetics, ROISYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityHideyaAndoDepartment of Applied Chemistry and Biotechnology, Okayama University of ScienceYoshioTsujinoGraduate School of Science, Technology, and Innovation, Kobe UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityResveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X3122024Epidemiology and clinical features of patients with tick bites in the Japanese spotted fever-endemic zone102570ENShinnosukeFukushimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaomiSumidaNumakuma HospitalOsamuKawamataNumakuma HospitalYoshimiHidaniNumakuma HospitalHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalPurpose: This study aimed to clarify the epidemiology and clinical features of tick bites in a Japanese spotted fever (JSF)-endemic area.<br>
Method: The clinical records of patients with tick bites were retrospectively reviewed based on a survey conducted at Numakuma Hospital, Fukuyama City, Hiroshima, Japan, from 2016 to 2023. Data on basic characteristics, visit dates, residential address, exposure activities, tick-bite sites, and prophylactic antimicrobial prescriptions for each patient with tick bites were collected at the JSF hotspot hospital.<br>
Results: A total of 443 patients with tick bites visited the hospital, of which data on 305 cases (68.8 %) were reviewed. The median age of these patients was 71 years, with a higher proportion of women (63.0 %). One-third of the patients had a preceding history of working in fields, whereas two-thirds had entered mountains or agricultural fields. Nearly 90 % of the patients visited the hospital from April to August, and the most common bite sites were the lower extremities (45.1 %). Most patients (76.1 %) resided in the southern area of Numakuma Hospital. Nearly all patients were prescribed prophylactic antibiotics (minocycline in 87.8 % of cases), and none subsequently developed JSF.<br>
Conclusion: Continued surveillance of patients with tick bites is warranted to better understand changes in the clinical impact of tick-borne diseases.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X3122024Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review102575ENShinnosukeFukushimaDepartment of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesShumaTsujiDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalHidemasaAkazawaDepartment of Infectious Diseases, Okayama University HospitalOsamuMatsushitaDepartment of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of Infectious Diseases, Okayama University HospitalIntroduction: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections.<br>
Methods: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including “Corynebacterium”, “Daptomycin", and "Resistance”, in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review.<br>
Results: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8 %), and prosthetic device-associated infections accounted for 66.7 % of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71 %–100 %) within 24 h of incubation, compared to other Corynebacterium strains.<br>
Conclusion: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-497114582025Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease881896ENYuiKambaraDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Medical SchoolHideakiFujiwaraDepartment of Hematology and Oncology, Okayama University HospitalAkiraYamamotoDepartment of Hematology and Oncology, Okayama University HospitalKazuyoshiGotohDepartment of Medical Laboratory Science, Okayama University Graduate School of Health SciencesShumaTsujiDepartment of Microbiology and Genetics, Okayama University Graduate School of Health SciencesMariKunihiroDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiOyamaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshikiTeraoDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAyameSatoDivision of Hospital Dentistry, Okayama University HospitalTakehiroTanakaDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDanielPeltierDivision of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of MedicineKeisukeSeikeDepartment of Hematology and Oncology, Okayama University HospitalHisakazuNishimoriDepartment of Hematology and Oncology, Okayama University HospitalNoboruAsadaDepartment of Hematology and Oncology, Okayama University HospitalDaisukeEnnishiCenter for Comprehensive Genomic Medicine, Okayama University HospitalKeikoFujiiDepartment of Clinical Laboratory, Okayama University HospitalNobuharuFujiiDivision of Blood Transfusion, Okayama University HospitalKen-ichiMatsuokaDepartment of Hematology and Oncology, Okayama University HospitalYoshihikoSogaDivision of Hospital Dentistry, Okayama University HospitalPavanReddyDan L Duncan Comprehensive Cancer Center, Baylor College of MedicineMaedaYoshinobuDepartment of Hematology and Oncology, Okayama University HospitalThe oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0016-70373912025Magnesium isotope composition of volcanic rocks from cold and warm subduction zones: Implications for the recycling of subducted serpentinites and carbonates158176ENWeiZhangThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityHiroshiKitagawaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityFangHuangCAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of ChinaMagnesium (Mg) isotopes are regarded as a sensitive tracer to the contribution from subducted serpentinites and carbonates. However, the source, distribution, and controlling factors of the Mg isotope composition of arc magmas remain unclear. In this study, we investigated the intra-arc and inter-arc variations in Mg isotope compositions of volcanic rocks from two typical cold subduction zones [NE Japan (NEJ) and Izu arcs] and a typical hot subduction zone [SW Japan (SWJ) arc] to address the question. The volcanic rocks from the frontal-arc regions of NEJ and Izu have isotopically heavy Mg (δ26Mg = –0.20 to –0.08 ‰) compared to the mantle-like δ26Mg values of most of volcanic rocks from SWJ and the rear regions of NEJ and Izu arcs (–0.28 to –0.17 ‰). It is also worth noting that NEJ arc includes samples with δ26Mg values (–0.61 to –0.39 ‰) significantly lower than the mantle, but similar to the < 110 Ma intra-continental basalts from eastern China, which is the first observation in modern arc rocks. No obvious effects of post-eruptive alteration, fractional crystallization, partial melting, or the addition of silicate-rich sediment and oceanic crust components could be identified in the Mg isotope compositions of these volcanic rocks. By contrast, the correlations between the δ26Mg values and the proxy for serpentinite component (i.e., 11B/10B and Nb/B ratios) indicate that the component exerts a strong control on the Mg-isotopic signature of these arc rocks. Considering metamorphic reactions in subduction lithologies under P-T conditions postulated for these arcs, the variations in δ26Mg values of these arc magmas are unlikely to have been controlled by dehydration of serpentinites in subducted oceanic lithosphere (slab serpentinite). Instead, the high-δ26Mg values of frontal-arc rocks are delivered by the fluids from serpentinite formed in the lowermost part of the sub-arc mantle (mantle wedge serpentinite) in channelized flow. Comparatively, such a high-δ26Mg signature is invisible in volcanic rocks from rear-arc regions of NEJ and Izu, and the entire SWJ, suggesting that the major Mg carriers in subducted serpentinites (e.g., talc, chlorite, and serpentine) were broken down completely before subducted slabs reached the depth beneath these volcanoes. Moreover, the volcanic rocks with low δ26Mg values from the rear arc of NEJ are characterized by high La/Yb and U/Nb ratios as well as low Ti/Eu, Ti/Ti*, and Hf/Hf* ratios, suggesting the involvements of carbonates in their magma sources. The quantitative modeling suggests that < 20 % of sedimentary carbonate (dolomite) was recycled into their mantle source, revealing that Mg-rich carbonate could be incorporated into a deep mantle wedge at rear-arc depths of 150–400 km in subduction zones.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-7991432024Capturing chronological variation in L2 speech through lexical measurements and regression analysis100105ENMarikoAbeOkayama UniversityYuichiroKobayashiNihon UniversityYusukeKondoWaseda UniversityThis study aims to bridge gaps in current research by analyzing a longitudinal spoken learner corpus of low-proficiency English learners. We investigated the chronological variation in lexical measurements in second language (L2) speaking production, focusing on data from 104 low-proficiency learners elicited eight times over 23 months. Our findings show that measures such as the number of different words and type-token ratio are effective indicators of L2 speaking development, whereas the use of sophisticated vocabulary was not significantly correlated with learning duration. These results suggest that in the early stages of L2 acquisition, speaking skills are influenced primarily by lexical variation. This finding underscores the importance of lexical variation as a key factor in novice-level L2 speaking proficiency.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X3122024Human Papillomavirus vaccination awareness and uptake among healthcare students in Japan102554ENMadokaShimbeDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalYoichiYamadaSchool of Pharmacy, Shujitsu UniversityFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: The vaccination rate for HPV (Human Papillomavirus) has remained significantly low in Japan because of the administrative suspension of active recommendation. This study investigates the awareness and uptake of the HPV vaccine among healthcare students in Japan following the reinstatement of active recommendation for young women in April 2022.<br>
Methods: A web-based survey was administered to 2567 healthcare students from Okayama and Shujitsu Universities in Japan in July 2023. The survey assessed participants' backgrounds, immunization status, awareness of vaccine recommendations, and knowledge of cervical cancer across various demographics, including sex, academic year, and department (Medicine, Health Science, Pharmaceutical, and Dentistry).<br>
Results: The response rate was 36.3 % (933 students; 181 male, 739 female, and 13 unspecified gender). The overall immunization rate among female students was 55.6 %, with higher rates observed in medical (73.8 %) and dental (63.0 %) students. Awareness of the government's change in vaccine recommendation was notably high among female and senior male students. Over half of the female students (54.7 %) reported receiving vaccinations based on their parents' advice. Among those unvaccinated but interested in future immunization, concerns about adverse reactions (47.4 %) and challenges in scheduling vaccinations (29.1 %) were predominant.<br>
Conclusion: Healthcare students exhibited a higher HPV vaccination rate than the general population. Ongoing education to improve vaccine literacy is crucial for augmenting HPV vaccination rates in Japan.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1053-24984422024Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor249260ENShinichiKawanaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikioOkazakiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohisaSakaueDepartment of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of MedicineKoheiHashimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroNakataDepartment of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University School of MedicineHarukiChoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinTanakaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentarohMiyoshiDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiOhtaniDepartment of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.<br>
Methods: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1−/−) mice.<br>
Results: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1−/− donors significantly improved pulmonary graft function compared to wild-type donors. Histological analysis showed decreased microvascular endothelial cell death, neutrophil infiltration, and albumin leakage. Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1−/− donors, correlating with diminished pulmonary edema. However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1−/− recipient.<br>
Conclusions: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0093-691X2282024Exogenous expression of PGC-1α during in vitro maturation impairs the developmental competence of porcine oocytes3036ENSon QuangDoDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHai ThanhNguyenDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityTakuyaWakaiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHiroakiFunahashiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityObjectives of the current study were to examine the effects of exogenous expression of PGC-1α, which is a transcription factor responsive for controlling mitochondrial DNA (mtDNA) replication, mitochondria quantity control, mitochondrial biogenesis, and reactive oxygen species (ROS) maintenance, in porcine oocytes during in-vitro maturation (IVM) on the developmental competence, as well as mitochondrial quantity and function. Exogenous over-expression of PGC-1α by injection of the mRNA construct into oocytes 20 h after the start of IVM culture significantly increased the copy number of mtDNA in the oocytes, but reduced the incidences of oocytes matured to the metaphase-II stage after the IVM culture for totally 44 h and completely suppressed the early development in vitro to the blastocyst stage following parthenogenetic activation. The exogenous expression of PGC-1α also significantly induced spindle defects and chromosome misalignments. Furthermore, markedly higher ROS levels were observed in the PGC-1α-overexpressed mature oocytes, whereas mRNA level of SOD1, encoded for a ROS scavenging enzyme, was decreased. These results conclude that forced expression of PGC-1α successfully increase mtDNA copy number but led to increased ROS production, evidently by downregulation of SOD1 gene expression, inducement of spindle aberration/chromosomal misalignment, and consequently reduction in the meiotic and developmental competences of porcine oocytes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0016-510710152025Short- and longer-term learning effects from virtual scale endoscopy videos: a useful tool for colorectal lesion size estimation (with videos)10301037.e5ENRyosukeHiraiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideakiKinugasaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMikakoIshiguroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunkiToyosawaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiAoyamaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShokoIgawaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasushiYamasakiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshihiroInokuchiDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroTakaharaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiKawanoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSakikoHiraokaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground and Aims: Accurate assessment of colorectal polyp size is crucial for determining treatment and surveillance policies. However, visual estimation of lesion diameter is often inaccurate, making simple and effective educational tools essential. We aimed to evaluate the learning effects of virtual scale endoscopy (VSE).<br>
Methods: Thirty-three endoscopists first watched prelearning videos for SET1. They then estimated the diameters of 20 lesions and referred to instructional videos with VSE for self-study. Subsequently, they watched the postlearning videos for SET2 and estimated the lesion diameters. The error between the estimated and correct lesion sizes of both sets was compared. To evaluate longer-term learning effects, participants answered SET3 and SET4, which consisted of the same questions as SET2 and SET1, respectively, but 2 to 3 months later without watching the instructional video for SET2.<br>
Results: The error in the participants’ estimation of the correct lesion diameter improved from SET1 to SET2 (34.7 ± 6.6 mm vs 30.7 ± 7.7 mm, P = .048), with a significant learning effect and error improvement specifically among nonexperts (35.2 ± 5.3 mm vs 30 ± 6.8 mm, P = .028). In SET3 and SET4, participants’ errors indicated that the learning effect was well maintained (SET2 vs SET3: 30.7 ± 7.7 mm vs 28.6 ± 7.2 mm [P = .1]; SET1 vs SET4: 34.7 ± 6.6 mm vs 31.7 ± 7.1 mm [P = .025]).<br>
Conclusions: VSE videos are a valuable learning tool for estimating lesion diameter, particularly for novice endoscopists, both in the short and longer term.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0093-691X2262024The impact of cumulus cell viability and pre-culture with the healthy cell mass on brilliant cresyl blue (BCB) staining assessment and meiotic competence of suboptimal porcine oocytes158166ENWanniarachchige Tharindu LakshithaFonsekaDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversitySon QuangDoDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityPhong NgocVanDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHai ThanhNguyenDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityTakuyaWakaiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHiroakiFunahashiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityObjectives of the present study were to investigate the characteristics including glucose-6-phosphate dehydrogenase activity, as determined by Brilliant Cresyl Blue (BCB) staining, of suboptimal porcine oocytes and to enhance the meiotic competence of those through pre-culture with cumulus cell masses (CCMs). Percentage of oocyte-cumulus complexes (OCCs) derived from small follicles (SF; <3 mm in diameter) containing the oocytes that were assessed as BCB-negative (BCB-) was significantly higher than those derived from medium follicles (MF; 3–6 mm in diameter). Degrees of dead cumulus cells were significantly higher in OCCs containing BCB- oocytes, regardless of the origin of OCCs (MF vs. SF), than those containing BCB-positive (BCB+) ones. Exposing OCCs containing BCB+ oocytes to the apoptosis inducer, carbonyl cyanide m-chlorophenylhydrazone, for 20 h significantly induced the transition to BCB- and meiotic progression of exposed OCCs were significantly reduced in both SF and MF derived ones. Transit of BCB- oocytes to BCB+ was induced when OCCs were pre-cultured with CCMs of MF derived OCCs containing BCB+ oocytes for 20 h before IVM. This pre-culture also significantly increased the meiotic competence of BCB- oocytes, particularly in SF derived ones. However, reactive oxygen species levels were significantly higher in BCB+ oocytes as compared with BCB- ones, regardless of pre-culture with CCMs, whereas no significant differences were found in the ATP contents among the treatment groups. In conclusion, the BCB result of oocytes could be regulated by the healthy status and content of surrounding cumulus cells and the meiotic competence of suboptimal BCB- porcine oocytes is improved by pre-culture with healthy CCMs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X3112025Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report102494ENKoheiOguniDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinnosukeFukushimaDepartment of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalAtsushiKatoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuhitoSuyamaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakehiroIwataDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiaMiyawakiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSawakoOnoDepartment of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease.
No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1544-6123652024Currency portfolios and global foreign exchange ambiguity105534ENTakaoAsanoFaculty of Economics, Okayama UniversityXiaojingCaiFaculty of Economics, Okayama UniversityRyutaSakemotoFaculty of Economics and Business, Hokkaido UniversityThis study investigates whether cross-sectional global foreign exchange (FX) ambiguity impacts currency portfolios. We observe that, in contrast to FX volatility, high FX ambiguity leads to high currency carry returns. We also reveal that FX ambiguity is weakly associated with the highest interest rate portfolio, but strongly related to the second highest interest rate portfolio. These results suggest that FX ambiguity captures elements of uncertainty that are not captured by FX volatility. In addition, FX ambiguity is not linked to returns on currency momentum and value portfolios.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1878-54093012024Initial trial of three‑lead wearable electrocardiogram monitoring in a full marathon2428ENKentaHiraiDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceNorikoSakanoDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceSusumuOozawaDepartment of Clinical Safety, Okayama University HospitalDaikiOusakaDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceYosukeKurokoDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceShingoKasaharaDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceSudden cardiac arrest during exercise can occur without prior warning signs at rest, highlighting the importance of monitoring for its prevention. To detect the signs of ischemic heart disease, including coronary artery anomalies, ST changes must be detected using three‑lead electrocardiograms (ECGs) corresponding to each region of the three coronary artery branches. We conducted ECG monitoring of five runners during a marathon using a wearable three‑lead ECG device (e-skin ECG; Xenoma Inc., Tokyo, Japan). Data without noise or artifacts were successfully collected for one of five runners during the entire marathon. Within the initial hour of the marathon, poor electrode adhesion to the skin hindered the data collection for the remaining four runners, which resulted in significantly decreased acquisition rate compared with the first hour (86.7 ± 13.4 % to 37.3 ± 36.9 %, p = 0.028). Couplets of premature ventricular contractions with clear ECG waveforms in the three leads were detected in one runner during the marathon. Further device improvements are necessary to enable marathon runners to obtain ECGs efficiently without affecting their performance. This study also demonstrated the potential applications of three‑lead wearable ECG monitoring for other short-duration sports and remote home-based cardiac rehabilitation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-26121262025Laparoscopic resection for oesophageal duplication cyst: A case report110572ENTomohiroHamazakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentoKawasakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiHashimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeTanabeDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction: Oesophageal duplication cyst is a congenital malformation and rare tumour, clinically manifesting as dysphagia, epigastric pain, or respiratory distress. Duplicate cysts associated with abscess formation or mediastinal penetration and malignancies have been reported, necessitating surgical resection. <br>
Presentation of case: A 55-year-old woman had chest discomfort for 1 year. Preoperative imaging, including computed tomography (CT), upper gastrointestinal endoscopy, and endoscopic ultrasound, revealed a tumour extending from the anterior wall to the lesser curvature of the near the oesophagogastric junction (OGJ) and a suspected mural nodule within the tumour. Contrast-enhanced CT revealed a cystic nodule on the wall of the lesser curvature of the OGJ, with an unclear boundary between the cystic nodule and the oesophageal wall. Magnetic resonance imaging showed an isointense signal on T1-weighted imaging and hyperintensity on T2weighted imaging. Laparoscopic lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed to the confirm mucinous cyst. Pathological findings revealed a cystic lesion in the muscularis propria of the OGJ filled with mucinous components and lined with multilayered columnar epithelial cells. The cyst was diagnosed as a duplicate without malignancy. <br>
Discussion: Since the border between the cyst and the oesophageal walls was unclear, and the cyst potentially contained a malignant component, instead of cystectomy, lower oesophagectomy and proximal gastrectomy with lymph node dissection were performed with oesophagogastric anastomosis using the double-flap technique, tailored specifically for OGJ cancer. <br>
Conclusions: Oesophageal duplication cysts are rare. Lower oesophagectomy and proximal gastrectomy are selective surgical approaches for cyst duplication at the OGJ.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X30062024Nonspecific N-terminal tetrapeptide insertions disrupt the translation arrest induced by ribosome-arresting peptide sequences107360ENAkinaoKoboSchool of Life Science and Technology, Tokyo Institute of TechnologyHidekiTaguchiSchool of Life Science and Technology, Tokyo Institute of TechnologyYuheiChadaniFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityThe nascent polypeptide chains passing through the ribosome tunnel not only serve as an intermediate of protein synthesis but also, in some cases, act as dynamic genetic information, controlling translation through interaction with the ribosome. One notable example is Escherichia coli SecM, in which translation of the ribosome arresting peptide (RAP) sequence in SecM leads to robust elongation arrest. Translation regulations, including the SecM-induced translation arrest, play regulatory roles such as gene expression control. Recent investigations have indicated that the insertion of a peptide sequence, SKIK (or MSKIK), into the adjacent N-terminus of the RAP sequence of SecM behaves as an "arrest canceler". As the study did not provide a direct assessment of the strength of translation arrest, we conducted detailed biochemical analyses. The results revealed that the effect of SKIK insertion on weakening SecM-induced translation arrest was not specific to the SKIK sequence, that is, other tetrapeptide sequences inserted just before the RAP sequence also attenuated the arrest. Our data suggest that SKIK or other tetrapeptide insertions disrupt the context of the RAP sequence rather than canceling or preventing the translation arrest.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X30032024Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling105679ENAtsushiMorimotoDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNobumasaTakasugiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYuexuanPanDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShoKubotaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoshiDohmaeBiomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource ScienceYumiAbikoGraduate School of Biomedical Science, Nagasaki UniversityKojiUchidaLaboratory of Food Chemistry, Graduate School of Agricultural and Life Sciences, The University of TokyoYoshitoKumagaiGraduate School of Pharmaceutical Sciences, Kyushu UniversityTakashiUeharaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityReactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as Cys in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed PI3K-Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K- Akt signaling by MVK reversed epidermal growth factor- induced negative regulation of autophagy and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K-Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K-Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071512024Protracted coronavirus disease 2019 after chimeric antigen receptor-T cell therapy successfully treated with sequential multidrug therapy102104ENMasahiroYamashitaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalNobuharuFujiiDepartment of Hematology and Oncology, Okayama University HospitalChiakiMatsumotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalMasanoriFujiiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKammeiRaiCenter for Innovative Clinical Medicine, Okayama University HospitalEikiIchiharaCenter for Clinical Oncology, Okayama University HospitalKadoakiOhashiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalA 56-year-old woman who received CD19 chimeric antigen receptor-T cell therapy for refractory diffuse large B-cell lymphoma developed severe coronavirus disease 2019 (COVID-19) and was treated with nirmatrelvir/ritonavir in April 2022. However, she experienced persistent fatigue and cough and fever in June. Computed tomography revealed bilateral ground-glass opacities (GGO), and the patient was treated with corticosteroids for organizing pneumonia after COVID19. Partial improvement was observed, but new GGO appeared despite corticosteroid therapy. Genome analysis of severe acute respiratory syndrome coronavirus 2 detected Omicron variant BA.1.1.2, which was prevalent at the time of initial infection. The patient was diagnosed with protracted COVID-19 and was treated with remdesivir, molnupiravir, nirmatrelvir/ritonavir, and tixagevimab/cilgavimab. These treatments appeared to contribute to the improvement of protracted COVID-19.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-8319102024Reduction with zinc - Impact on the determination of nitrite and nitrate ions using microfluidic paper-based analytical devices100347ENMika I.UmedaOkayama UniversityKaewtaDanchanaOkayama UniversityTakatoshiFujiiNational Institute of Technology, Yonago CollegeEiichiHinoNational Institute of Technology, Yonago CollegeYusukeDateNational Institute of Technology, Yonago CollegeKaoruAokiNational Institute of Technology, Yonago CollegeTakashiKanetaOkayama UniversityWe used a microfluidic paper-based analytical device (mu PAD) to investigate the influence that zinc reduction exerts on the determination of nitrite and nitrate ions in natural water samples. The mu PAD consists of layered channels for the reduction of nitrate to nitrite with zinc powder and the subsequent detection of nitrite with Griess reagent. The amount of zinc, number of layers, and reaction time for the reduction were optimized to obtain an intense signal for nitrate. Initially, the sensitivity to nitrate corresponded to 55% that of nitrite, which implied an incomplete reduction. We found, however, that zinc decreased the sensitivity to nitrite in both the mu PAD and spectrophotometry. The sensitivity to nitrite was decreased by 48% in spectrophotometry and 68% in the mu PAD following the reaction with zinc. One of the reasons for the decreased sensitivity is attributed to the production of ammonia, as we elucidated that both nitrite and nitrate produced ammonia via the reaction with zinc. The results suggest that the total concentration of nitrite and nitrate must be corrected by constructing a calibration curve for nitrite with zinc, in addition to developing curves for nitrate with zinc and for nitrite without zinc. Using these calibration curves, the absorbance at different concentration ratios of nitrite and nitrate ions could be reproduced via calculation using the calibration curves with zinc for nitrite and nitrate. Eventually, the developed mu PAD was applied to the determination of nitrite and nitrate ions in natural water samples, and the results were compared with those using a conventional spectrophotometric method. The results of the mu PAD are in good agreement with those of conventional spectrophotometry, which suggests that the mu PAD is reliable for the measurement of nitrite and nitrate ions in natural water samples.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-844010132024Resolvin D2-induced reparative dentin and pulp stem cells after pulpotomy in a rat modele34206ENMitsuhiroYonedaDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalHidetakaIdeguchiDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinNakamuraDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern UniversityZulemaAriasDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMitsuakiOnoDepartment of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiYamamotoThe Center for Graduate Medical Education (Dental Division), Okayama University HospitalShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Vital pulp therapy (VPT) is performed to preserve dental pulp. However, the biocompatibility of the existing materials is of concern. Therefore, novel materials that can induce pulp healing without adverse effects need to be developed. Resolvin D2 (RvD2), one of specialized pro-resolving mediators, can resolve inflammation and promote the healing of periapical lesions. Therefore, RvD2 may be suitable for use in VPT. In the present study, we evaluated the efficacy of RvD2 against VPT using in vivo and in vitro models.<br>
Methods: First molars of eight-week-old male Sprague–Dawley rats were used for pulpotomy. They were then divided into three treatment groups: RvD2, phosphate-buffered saline, and calcium hydroxide groups. Treatment results were assessed using radiological, histological, and immunohistochemical (GPR18, TNF-α, Ki67, VEGF, TGF-β, CD44, CD90, and TRPA1) analyses. Dental pulp-derived cells were treated with RvD2 in vitro and analyzed using cell-proliferation and cell-migration assays, real-time PCR (Gpr18, Tnf-α, Il-1β, Tgf-β, Vegf, Nanog, and Trpa1), ELISA (VEGF and TGF-β), immunocytochemistry (TRPA1), and flow cytometry (dental pulp stem cells: DPSCs).<br>
Results: The formation of calcified tissue in the pulp was observed in the RvD2 and calcium hydroxide groups. RvD2 inhibited inflammation in dental pulp cells. RvD2 promoted cell proliferation and migration and the expression of TGF-β and VEGF in vitro and in vivo. RvD2 increased the number of DPSCs. In addition, RvD2 suppressed TRPA1 expression as a pain receptor.<br>
Conclusion: RvD2 induced the formation of reparative dentin, anti-inflammatory effects, and decreased pain, along with the proliferation of DPSCs via the expression of VEGF and TGF-β, on the pulp surface in pulpotomy models.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2590-1230232024Crystal plasticity analysis of fatigue crack initiation site considering crystallographic orientation in Ti-22V-4Al alloy102405ENJintaArakawaGraduate School of Natural Science and Technology, Okayama UniversityKokiHirazumiGraduate School of Natural Science and Technology, Okayama UniversityTakeshiUemoriGraduate School of Natural Science and Technology, Okayama UniversityYoshitoTakemotoGraduate School of Natural Science and Technology, Okayama UniversityIn this study, plane bending fatigue tests were conducted on Ti-22V-4Al alloy, a beta-type titanium alloy, to examine the fatigue crack initiation behavior in detail. In addition, the prediction of fatigue crack initiation points was investigated from the perspectives of the Schmidt factor (SF) and crystal plasticity finite element method (CP-FEM). The slip system contributing to fatigue crack initiation can be accurately predicted by assessing the magnitude relationship of SF. Also, this prediction is already indicated in a lot of paper by using out of component of slip activity. However, the location where the fatigue crack will occur can be not estimated by SF on polycrystalline. Therefore, prediction of grains where fatigue cracks will occur could be achieved with high accuracy by constructing a CP-FEM that considers the mechanical interaction of polycrystals and grain boundary. Utilizing advanced methodologies such as CP-FEM and numerical calculation techniques, it is strictly investigated that the factors influencing fatigue crack initiation in polycrystalline materials. Our research concluded the understanding of fatigue crack initiation on polycrystal grains by considering the mechanical interaction of polycrystals and grain boundary.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0016-510710052024Virtual indigo carmine chromoendoscopy images: A novel modality for peroral cholangioscopy using artificial intelligence technology (with video)938946.e1ENRyosukeSatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalHideakiKinugasaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMasahiroTomiyaBusiness Strategy Division, Ryobi Systems Co, LtdTakayoshiTanimotoBusiness Strategy Division, Ryobi Systems Co, LtdAkimitsuOhtoBusiness Strategy Division, Ryobi Systems Co, LtdKeiHaradaDepartment of Gastroenterology and Hepatology, Okayama University HospitalNaoHattoriDepartment of Gastroenterology and Hepatology, Okayama University HospitalTaisukeObataDepartment of Gastroenterology and Hepatology, Okayama University HospitalAkihiroMatsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalKazuyaMiyamotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalKosakuMorimotoDepartment of Gastroenterology and Hepatology, Okayama University HospitalHiroyukiTerasawaDepartment of Gastroenterology and Hepatology, Okayama University HospitalYukiFujiiDepartment of Gastroenterology and Hepatology, Okayama University HospitalDaisukeUchidaDepartment of Gastroenterology and Hepatology, Okayama University HospitalKoichiroTsutsumiDepartment of Gastroenterology and Hepatology, Okayama University HospitalShigeruHoriguchiDepartment of Gastroenterology and Hepatology, Okayama University HospitalHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University HospitalYoshiroKawaharaDepartment of Gastroenterology and Hepatology, Okayama University HospitalMotoyukiOtsukaDepartment of Gastroenterology and Hepatology, Okayama University HospitalBackground and Aims: Accurately diagnosing biliary strictures is crucial for surgical decisions, and although peroral cholangioscopy (POCS) aids in visual diagnosis, diagnosing malignancies or determining lesion margins via this route remains challenging. Indigo carmine is commonly used to evaluate lesions during GI endoscopy. We aimed to establish the utility of virtual indigo carmine chromoendoscopy (VICI) converted from POCS images using artificial intelligence.<br>
Methods: This single-center, retrospective study analyzed 40 patients with biliary strictures who underwent POCS using white-light imaging (WLI) and narrow-band imaging (NBI). A cycle-consistent adversarial network was used to convert the WLI into VICI of POCS images. Three experienced endoscopists evaluated WLI, NBI, and VICI via POCS in all patients. The primary outcome was the visualization quality of surface structures, surface microvessels, and lesion margins. The secondary outcome was diagnostic accuracy.<br>
Results: VICI showed superior visualization of the surface structures and lesion margins compared with WLI (P < .001) and NBI (P < .001). The diagnostic accuracies were 72.5%, 87.5%, and 90.0% in WLI alone, WLI and VICI simultaneously, and WLI and NBI simultaneously, respectively. WLI and VICI simultaneously tended to result in higher accuracy than WLI alone (P = .083), and the results were not significantly different from WLI and NBI simultaneously (P = .65).<br>
Conclusions: VICI in POCS proved valuable for visualizing surface structures and lesion margins and contributed to higher diagnostic accuracy comparable to NBI. In addition to NBI, VICI may be a novel supportive modality for POCS.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1063-458432112024Inverse genetics tracing the differentiation pathway of human chondrocytes14191432ENH.T.DoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesM.OnoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesZ.WangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesW.KitagawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA.T.DangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.YonezawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.KubokiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesT.OohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesS.KubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjective: Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a limited population of the cells that pass through a particular pathway can metamorphose into iPSCs, while the others do not. This study aimed to clarify the pathways that chondrocytes follow during the reprogramming process.<br>
Design: The fate of human articular chondrocytes under reprogramming was investigated through a time-coursed single-cell transcriptomic analysis, which we termed an inverse genetic approach. The iPS interference technique was also employed to verify that chondrocytes inversely return to pluripotency following the proper differentiation pathway.<br>
Results: We confirmed that human chondrocytes could be converted into cells with an iPSC phenotype. Moreover, it was clarified that a limited population that underwent the silencing of SOX9, a master gene for chondrogenesis, at a specific point during the proper transcriptome transition pathway, could eventually become iPSCs. Interestingly, the other cells, which failed to be reprogrammed, followed a distinct pathway toward cells with a surface zone chondrocyte phenotype. The critical involvement of cellular communication network factors (CCNs) in this process was indicated. The idea that chondrocytes, when reprogrammed into iPSCs, follow the differentiation pathway backward was supported by the successful iPS interference using SOX9.<br>
Conclusions: This inverse genetic strategy may be useful for seeking candidates for the master genes for the differentiation of various somatic cells. The utility of CCNs in articular cartilage regeneration is also supported.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1547-527121102024Risk stratification for the occurrence of ventricular fibrillation in patients with early repolarization syndrome17871794ENHiroshiMoritaDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSaoriAsadaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryAkiraUeokaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryTomofumiMizunoDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryTakuroMasudaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryMasakazuMiyamotoDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistrySatoshiKawadaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryKojiNakagawaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryNobuhiroNishiiDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinsukeYuasaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine and DentistryBackground Several signs of malignant early repolarizations have been proposed in patients with early repolarization syndrome (ERS). However, reports have challenged the efficacy of these signs in predicting future ventricular fibrillation (VF) in patients with ERS.<br>
Objective This study aimed to assess the predictive value of various electrocardiogram (ECG) markers for future VF events in patients with ERS.<br>
Methods We retrospectively evaluated the clinical characteristics of 44 patients with ERS to identify risk factors for VF during follow-up.<br>
Results After the initial event, 16 patients experienced VF (VF group), whereas 28 did not (non-VF group). The VF group had a longer QRS interval, more fragmented QRS (fQRS), and a higher T/R voltage ratio than the non-VF group. Wide J waves were more prevalent in the VF group; however, other J-wave markers did not differ between the groups. Positive late potentials recorded on signal-averaged ECGs were more frequent in the VF group. Whereas none of the patients showed spontaneous Brugada syndrome on ECG, the VF group frequently exhibited pilsicainide-induced ST-segment elevation. These ECG markers were significantly associated with the occurrence of VF during follow-up. Patients with multiple ECG factors, including QRS abnormalities (wide QRS or fQRS), wide J waves, and a high T/R ratio, had a worse prognosis than patients without multiple factors, effectively stratifying patient risk.<br>
Conclusion The occurrence of VF in patients with ERS may be associated with conduction abnormalities such as QRS widening, fQRS, high T/R ratio, positive late potentials, and pilsicainide test results. Therefore, ECG factors could be useful in identifying high-risk patients.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0958-39474942024Evaluation of the trend of set-up errors during the treatment period using set-up margin in prostate radiotherapy291297ENHinakoSasakiDepartment of Radiological Technology, Faculty of Health Sciences, Okayama University Medical SchoolTakumiMorishitaDepartment of Radiological Technology, Faculty of Health Sciences, Okayama University Medical SchoolNahoIrieDepartment of Radiological Technology, Faculty of Health Sciences, Okayama University Medical SchoolRenaKojimaDepartment of Radiological Technology, Faculty of Health Sciences, Okayama University Medical SchoolTetsukazuKiriyamaDepartment of Radiology, Uwajima City HospitalAkiraNakamotoDepartment of Radiology, Tokuyama Central HospitalKunioNishiokaDepartment of Radiology, Tokuyama Central HospitalShotaroTakahashiDepartment of Radiology, Tokuyama Central HospitalYoshinoriTanabeDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityAccurate information on set-up error during radiotherapy is essential for determining the optimal number of treatments in hypofractionated radiotherapy for prostate cancer. This necessitates careful control by the radiotherapy staff to assess the patient's condition. This study aimed to develop an evaluation method of the temporal trends in a patient's specific prostate movement during treatment using image matching and margin values. This study included 65 patients who underwent prostate volumetric modulated arc therapy (mean treatment time, 87.2 s). Set-up errors were assessed using bone, inter-, and intra-fraction marker matching across 39 fractions. The set-up margin was determined by dividing the four periods into 39 fractions using Stroom's formula and correlation coefficient. The intra-fraction set-up error was biased in the anterior-superior (AS) direction during treatment. The temporal trend of set-up errors during radiotherapy slightly increased based on bone matching and inter-fraction marker matching, with a 1.6-mm difference in the set-up margin fractions 11 to 20. The correlation coefficient of the mean prostate movement during treatment significantly decreased in the superior-inferior direction, while remaining high in the left-right and anterior-posterior directions. Image matching contributed significantly to the improvement of set-up errors; however, careful attention is needed for prostate movement in the AS direction, particularly during short treatment times. Understanding the trend of set-up errors during the treatment period is essential in numerical information sharing on patient condition and evaluating the margins for tailored hypo-fractionated radiotherapy, considering the facility's image-guided radiation therapy technology.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-39408202024Neurogenesis impairment with glial activation in the hippocampus-connected regions of intracerebroventricular streptozotocin-injected mice137598ENKaoriMasaiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYutaNakayamaDepartment of Medical Neurobiology, Okayama University Medical SchoolKotaroShinDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChiakiSugaharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIkukoMiyazakiDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoAsanumaDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAdult neurogenesis in the hippocampus and subventricular zone (SVZ) is impaired by intracerebroventricular administration of streptozotocin (icv-STZ) to rodents. Although neural cells in the several brain regions which connect with the hippocampus or SVZ is thought to be involved in the adult neurogenesis, few studies have investigated morphological alterations of glial cells in these areas. The present study revealed that icv-STZ induces reduction of neural progenitor cells and a dramatic increase in reactive astrocytes and microglia especially in the hippocampus and various hippocampus-connected brain areas. In contrast, there was no significant neuronal damage excluding demyelination of the stria medullaris. The results indicate the hippocampal neurogenesis impairment of this model might be occurred by activated glial cells in the hippocampus, or hippocampus-connected regions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-844010112024Bacterial DNA and serum IgG antibody titer assays for assessing infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogse31872ENMasakoTai-TokuzenDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalTakashiItoCenter for Innovative Clinical Medicine, Okayama University HospitalKazuyaTamuraDepartment of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoHirayamaDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityHirohitoOgawaDepartment of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinNakamuraCenter for Collaborative Research, Department of Oral Science and Translational Research, Nova Southeastern UniversityKeisukeOkuboDepartment of Periodontics and Endodontics, Division of Dentistry, Okayama University HospitalKazuhiroOmoriDepartment of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiYamamotoDepartment of Comprehensive Dentistry, The Center for Graduate Medical Education (Dental Division), Okayama University HospitalKatsumiMominokiDepartment of Animal Resources, Advanced Science Research Center, Okayama UniversityShogoTakashibaDepartment of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPeriodontal disease is highly prevalent in both humans and dogs. Although there have been reports of cross-infection of periodontopathic bacteria, methods for assessing it have yet to be established. The actual status of cross-infection remains to be seen. The purpose of this study was to evaluate the utility of bacterial DNA and serum immunoglobulin G (IgG) antibody titer assays to assess infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs. Four experimental beagles were used for establishing methods. Sixty-six companion dogs at veterinary clinics visiting for treatment and prophylaxis of periodontal disease were used and divided into healthy, gingivitis, and periodontitis groups. Periodontal pathogens such as Porphyromonas gingivalis and Porphyromonas gulae were investigated as target bacteria. DNA levels of both bacteria were measured using species-specific primers designed for real-time polymerase chain reaction (PCR). Serum IgG titers of both bacteria were measured by enzyme-linked immunosorbent assay (ELISA).<br>
PCR primers were confirmed to have high sensitivity and specificity. However, there was no relationship between the amount of bacterial DNA and the severity of the periodontal disease. In addition, dogs with periodontitis had higher IgG titers against both bacteria compared to dogs in the healthy and gingivitis groups; there was cross-reactivity between the two bacteria. Receiver operating characteristic (ROC) analysis of IgG titers against both bacteria showed high sensitivity (>90 %) and specificity (>75 %). Since both bacteria were distinguished by DNA assays, the combination of these assays may be useful in the evaluation of cross-infection.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-1864352024Effects of cellulose nanofibers on soil water retention and aggregate stability103650ENAn ThuyNgoGraduate School of Environmental and Life Science, Okayama UniversityYasushiMoriGraduate School of Environmental and Life Science, Okayama UniversityLong ThanhBuiGraduate School of Environmental and Life Science, Okayama UniversityInnovative solutions that address global challenges such as water scarcity and soil erosion are critical for maintaining sustainable agriculture. Due to their water-absorbing and soil-binding properties, cellulose nanofibers (CNF) can be applied to soil to enhance soil water retention and aggregate stability. In this study, we analyzed the effects of the drying temperature, dosage, irrigation water quality, and soil type on the efficacy of CNFs. Our results revealed that CNF dried at 5 degrees C is more effective at absorbing water than others, and adding 1% CNF enhanced soil water content up to 98%. The CNF samples absorbed water due to their hydrophilic molecular groups and morphological structure, as confirmed by Fourier-transform infrared spectroscopy and scanning electron microscopy. CNF addition increased the soil volumetric water content and prolonged water retention by 22 days in the paddy soil samples, highlighting its potential for drought-prone areas. Furthermore, irrigation water quality, such as pH and cation values, influenced the interactions between CNF and water molecules, suggesting adjustments to the water retention curve. In its hydrated state, CNF promotes colloid flocculation and binds to soil particles, thereby strengthening the bonds crucial for aggregate formation and stability. CNF enhanced macro-aggregate formation by up to 48% and 59% in the masa and paddy soil samples, respectively. Our study emphasizes the potential of CNF for water conservation, soil health, and overall agricultural sustainability.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-26121182024The effectiveness of palliative middle meningeal artery embolization prior to craniotomy for large acute epidural hematoma: A case report109704ENYuichiHirataDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuTakahashiDepartment of Neurological Surgery, Kagawa Prefectural Central HospitalSatoshiKuramotoDepartment of Neurological Surgery, Kagawa Prefectural Central HospitalShingoNishihiroDepartment of Neurological Surgery, Kagawa Prefectural Central HospitalYasuhiroOnoDepartment of Neurological Surgery, Kagawa Prefectural Central HospitalTomotsuguIchikawaDepartment of Neurological Surgery, Kagawa Prefectural Central HospitalIntroduction and importance: Acute epidural hematoma is typically managed with craniotomy. However, there are a few reports on transcatheter arterial embolization (TAE) as an adjunctive therapy. <br>
Case presentation: A 70-year-old female with no obvious history of trauma was transported to our hospital. Computed tomography scan revealed an epidural hematoma of approximately 80 ml with a midline shift of 5 mm. We decided to perform an emergency craniotomy. However, the operating room (OR) was already occupied by a scheduled surgery and it would take 30 min to an hour to prepare it. We opted to wait for our OR, considering that, even if the patient was transferred to another hospital, it would take time for the craniotomy to commence. <br>
Clinical discussion: We performed TAE for the middle meningeal artery (MMA) as a palliative measure to prevent hematoma enlargement. The MMA was selectively embolized with 20 % n-butyl-2-cyanoacrylate (NBCA), resulting in no hematoma enlargement or observed complications. The criteria for endovascular treatment of acute epidural hematoma are not yet well-established. This case demonstrates the potential role of endovascular treatment for large acute epidural hematomas in carefully selected patients. <br>
Conclusion: If there is a time gap before craniotomy, TAE could be considered a viable option for large acute epidural hematomas as a palliative intervention before craniotomy.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1201-97121412024Vibriosis in South Asia: A systematic review and meta-analysis106955ENBasilua AndreMuzemboGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiKitaharaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAyumuOhnoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJanukaKhatiwadaSocial Work InstituteShantaDuttaDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesShin-IchiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjectives: South Asia remains home to foodborne diseases caused by the Vibrio species. We aimed to compile and update information on the epidemiology of vibriosis in South Asia. <br>
Methods: For this systematic review and meta-analysis, we searched PubMed, Web of Science, EMBASE, and Google Scholar for studies related to vibriosis in South Asia published up to May 2023. A random-effects meta-analysis was used to estimate the pooled isolation rate of non-cholera-causing Vibrio species. <br>
Results: In total, 38 studies were included. Seven of these were case reports and 22 were included in the meta-analysis. The reported vibriosis cases were caused by non-O1/non-O139 V. cholerae, V. parahaemolyticus, V. fluvialis, and V. vulnificus. The overall pooled isolation rate was 4.0% (95% confidence interval [CI] 3.0-5.0%) in patients with diarrhea. Heterogeneity was high (I-2 = 98.0%). The isolation rate of non-O1/non-O139 V. cholerae, V. parahaemolyticus, and V. fluvialis were 9.0 (95% CI 7.0-10.0%), 1.0 (95% CI 1.0-2.0%), and 2.0 (95% CI: 1.0-3.0%), respectively. Regarding V. parahaemolyticus, O3:K6 was the most frequently isolated serotype. Cases peaked during summer. Several studies reported antibiotic-resistant strains and those harboring extended-spectrum beta-lactamases genes. <br>
Conclusions: This study demonstrates a high burden of infections caused by non-cholera-causing Vibrio species in South Asia.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-831992024Radiation evaluation assay using a human three-dimensional oral cancer model for clinical radiation therapy.100297ENLucieSercombeBiomedical Engineering Department, Grenoble Institute of TechnologyKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityKenjiIzumiDivision of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata UniversityWith the development of various radiation -based cancer therapies, radiobiological evaluation methods instead of traditional clonogenic assays with monolayer single cell culture are required to bridge gaps in clinical data. Heterogeneity within cancer tissues is the reason for bridging the gap between basic and clinical research in cancer radiotherapy. To solve this problem, we investigated an evaluation assay using a three-dimensional (3D) model of cancer tissue. In this study, a 3D model consisting of tumor and stromal layers was used to compare and verify radiobiological effects with conventional two-dimensional (2D) methods. A significant difference in the response to radiation was observed between the 2D and 3D models. The relative number of cancer cells decreased with X-ray dose escalations in the 2D and 3D models. In contrast, the relative number of normal cells was quite different between the 2D and 3D models. Considering the ability of cells to recover from radiation-induced damage, the histological results of the 3D model were reflected in the clinical data. Histopathological analysis using a 3D model is a potential method for evaluating radiobiological effects on the tumor and tumor margins.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-22756532024Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes100510ENMasatoKomaiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukaNodaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsuyaIkedaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNanakaKaneshiroDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYujiKamikuboDepartment of Cellular and Molecular Pharmacology, Juntendo University Graduate School of MedicineTakashiSakuraiDepartment of Cellular and Molecular Pharmacology, Juntendo University Graduate School of MedicineTakashiUeharaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNobumasaTakasugiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe link between changes in astrocyte function and the pathological progression of Alzheimer's disease (AD) has attracted considerable attention. Interestingly, activated astrocytes in AD show abnormalities in their lipid content and metabolism. In particular, the expression of apolipoprotein E (ApoE), a lipid transporter, is decreased. Because ApoE has anti-inflammatory and amyloid β (Aβ)-metabolizing effects, the nuclear receptors, retinoid X receptor (RXR) and LXR, which are involved in ApoE expression, are considered promising therapeutic targets for AD. However, the therapeutic effects of agents targeting these receptors are limited or vary considerably among groups, indicating the involvement of an unknown pathological factor that modifies astrocyte and ApoE function. Here, we focused on the signaling lipid, sphingosine-1-phosphate (S1P), which is mainly produced by sphingosine kinase 2 (SphK2) in the brain. Using astrocyte models, we found that upregulation of SphK2/S1P signaling suppressed ApoE induction by both RXR and LXR agonists. We also found that SphK2 activation reduced RXR binding to the APOE promoter region in the nucleus, suggesting the nuclear function of SphK2/S1P. Intriguingly, suppression of SphK2 activity by RNA knockdown or specific inhibitors upregulated lipidated ApoE induction. Furthermore, the induced ApoE facilitates Aβ uptake in astrocytes. Together with our previous findings that SphK2 activity is upregulated in AD brain and promotes Aβ production in neurons, these results indicate that SphK2/S1P signaling is a promising multifunctional therapeutic target for AD that can modulate astrocyte function by stabilizing the effects of RXR and LXR agonists, and simultaneously regulate neuronal pathogenesis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-7616592023Solid-state inorganic and metallic adhesives for soft biological tissues439445ENMasahiroOkadaDepartment of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakuyaMatsumotoDepartment of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCurrently, the soft-tissue adhesives used in clinical practice are glue-type organic adhesives. However, there is a demand for new types of adhesives, because the current organic adhesives present challenges in terms of their biocompatibility and adhesion strength. This review summarizes the discovery and development of inorganic and metallic adhesives designed for soft biological tissues while focusing on immobilization of medical divices on soft tissues. These new types of adhesives are in a solid state and adhere directly and immediately to soft tissues. Therefore, they are called "solid-state adhesives" to distinguish them from the currently used glue-type adhesives. In previous studies on inorganic solid-state adhesives, oxides and calcium phosphates were used as raw materials in the form of nanoparticles, nanoparticle-coated films, or nanoparticle-assembled porous plates. In previous studies on metallic solid-state adhesives, only Ti and its alloys were used as raw materials. This review also discusses the future perspectives in this active research area.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-2507222023Video-assisted transarterial modified Konno procedure with concurrent myectomy for hypertrophic obstructive cardiomyopathy261264ENHiroyukiSuzukiDepartment of Cardiovascular Surgery, Okayama UniversityYasuhiroKotaniDepartment of Cardiovascular Surgery, Okayama UniversityShunjiSanoDivision of Pediatric Cardiac Surgery, Pediatric Heart Disease & Adult Congenital Heart Disease Center, Showa University HospitalShingoKasaharaDepartment of Cardiovascular Surgery, Okayama UniversityNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0925-96351402023Molecular dynamics simulation of deposition of amorphous carbon films on sapphire surfaces110514ENQiangYueGraduate School of Natural Science and Technology, Okayama UniversityTakayoshiYokoyaResearch Institute for Interdisciplinary Science, Okayama UniversityYujiMuraokaResearch Institute for Interdisciplinary Science, Okayama UniversityThe growth of amorphous carbon films on a sapphire surface was investigated using classical molecular dynamics simulation. The kinetic energy of carbon particles was set as 10 eV and ReaxFF potential was used to express the interaction between different kinds of particles. The results of the temperature distribution in both deposition time and deposition space are reported. Simulation results reveal that the grown amorphous carbon film consists of four regions, namely interlayer, low density, stable growth, and surface regions. In the interlayer region, the interlayer between substrate and pure carbon film is formed. In the low density region, a pure carbon film is grown while the film density decreases initially and then increases. In the stable growth region, the film density remains almost constant. The film density decreases rapidly in the surface region. The radial distribution function (RDF) analysis suggests that a structure similar to that of diamond exists in the stable growth region of the film. The lower film density in the low density and surface regions was interpreted to indicate the existence of abundant sp1 chain structures, which is supported by the depth profile of the sp fractions. The present results are in good agreement with previous experimental and simulation results and demonstrate the suitability of the ReaxFF potential in the simulation of amorphous carbon growth on sapphire substrate. Our study provides a good starting point for the simulation study of amorphous carbon films on sapphire substrates.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-5204162023Treatment patterns and clinician stress related to care of out-of-hospital cardiac arrest patients with a do not attempt resuscitation order100507ENRyoTanabeDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJonathanElmerDepartment of Emergency Medicine, University of PittsburghHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityObjective: This research investigated treatment patterns for out-of-hospital cardiac arrest patients with Do Not Attempt Resuscitation orders in Japanese emergency departments and the associated clinician stress.<br>
Methods: A cross-sectional survey was conducted at 9 hospitals in Okayama, Japan, targeting emergency department nurses and physicians. The questionnaire inquired about the last treated out-of-hospital cardiac arrest patient with a Do Not Attempt Resuscitation. We assessed emotional stress on a 0–10 scale and moral distress on a 1–5 scale among clinicians.<br>
Results: Of 208 participants, 107 (51%) had treated an out-of-hospital cardiac arrest patient with a Do Not Attempt Resuscitation order in the past 6 months. Of these, 65 (61%) clinicians used a “slow code” due to perceived futility in resuscitation (42/65 [65%]), unwillingness to terminate resuscitation upon arrival (38/65 [59%]), and absence of family at the time of patient’s arrival (35/65 [54%]). Female clinicians had higher emotional stress (5 vs. 3; P = 0.007) and moral distress (3 vs. 2; P = 0.002) than males. Nurses faced more moral distress than physicians (3 vs. 2; P < 0.001). Adjusted logistic regression revealed that having performed a “slow code” (adjusted odds ratio, 5.09 [95% CI, 1.68–17.87]) and having greater ethical concerns about “slow code” (adjusted odds ratio, 0.35 [95% CI, 0.19–0.58]) were associated with high stress levels.<br>
Conclusions: The prevalent use of “slow code” for out-of-hospital cardiac arrest patients with Do Not Attempt Resuscitation orders underscores the challenges in managing these patients in clinical practice.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2590-05955122023Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study100733ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiNakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKensakuTakahashiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakafumiMoritaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroOnishiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesRationale & Objective: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants.<br>
Study Design: Retrospective cohort study.<br>
Setting & Participants: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled.<br>
Predictors: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score.<br>
Outcomes: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy.<br>
Analytical Approach: Cox proportional hazards model.<br>
Results: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91).<br>
Limitations: Single-center study and small sample size.<br>
Conclusions: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1350-63071532023Prediction of slip activity of crystal grains around semi-circular and semi-elliptical notches in thin-sheet specimens of pure titanium using formulated macroscopic stress distribution and crystal orientation107623ENNaoyaTadaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTakeshiUemoriFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityJunjiSakamotoFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityThin metal sheets and wires are important materials for various devices used in electrical, mechanical, and medical fields. With the downsizing of these devices, demand for thinner sheets and wires has increased. Amongst the many metals available, pure titanium has been attracting much attention for use in medical and dental devices because of its good biocompatibility in addition to its light weight and high corrosion resistance. However, thin metal sheets and wires are usually polycrystalline materials and, with the downsizing of materials, there is a loss of homogeneity during deformations. Inhomogeneous deformation becomes significant in thin sheets and wires, owing to the different crystal orientations and geometries of crystal grains. Furthermore, the shapes of such devices are not uniform, unlike, say, a simple rod. Therefore, macroscopic stress and strain concentrations should be taken into consideration when designing these devices as they affect the localization of deformation and the resultant fracture. In this study, semi-circular and semi-elliptical notched specimens made of thin-sheet polycrystalline pure titanium are subjected to tensile testing. Inhomogeneous deformation caused by crystallographic slip is observed near the notch root. Analysis of the crystal orientation and observation of the slip line show that the slip initiation in crystal grains is affected by the macroscopic stress distribution and can be predicted from the slip activity calculated from both the critical resolved shear stress on the slip systems and the resolved shear stress acting on prospective slip planes obtained from the macroscopic multiaxial stress distribution.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0093-691X2102023Negative correlations of mitochondrial DNA copy number in commercial frozen bull spermatozoa with the motility parameters after thawing154161ENHai ThanhNguyenDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversitySon QuangDoDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHiroshiKobayashiOkayama Prefectural Center for Animal Husbandry and ResearchTakuyaWakaiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityHiroakiFunahashiDepartment of Animal Science, Graduate School of Environmental and Life Science, Okayama UniversityThe purpose of the current study was to investigate the relationship between mitochondrial content of commercial frozen-thawed bull spermatozoa and motility. Firstly, mitochondrial DNA copy number per spermatozoon (MDCN), mitochondrial content (MC), the percentage of spermatozoa with high mitochondrial membrane potential (HMMP), intracellular reactive oxygen species (ROS) and motility parameters of frozen-thawed spermatozoa derived from five bulls were determined by using qPCR, flow cytometry and CASA, respectively, and analyzed the relationships. Results showed that all parameters examined, including MDCN, MC, HMMP, ROS and motility indicators, significantly differed among frozen spermatozoa from different bulls. Both MDCN and MC were negatively correlated with HMMP and motility indicators, but positively with ROS, of course, whereas there was a highly positive relationship between MDCN and MC. Secondly, when MDCN and MC were examined in frozen spermatozoa prepared at different points in the lives of four bulls, those did not correlate overall throughout their lives (1.3–14.3 years old), but did correlate significantly in two sires. From these results, we conclude that MDCN and MC of frozen spermatozoa differ among sires, and are negatively correlated with HMMP and sperm motility parameters, probably due to mitochondrial oxidative stress resulted in the presence of ROS, demonstrating that these appear to be useful markers to assess sires’ spermatozoa. It should be noted that the MDCN and MC of bull spermatozoa may not vary overall with the age of the sire, whereas those changes with age in some individuals and may affect sperm motility.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0003-267012782023Determination of mass-dependent chromium isotopic compositions in geological samples by double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS)341723ENDilan M.RatnayakeThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityRyojiTanakaThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityEizoNakamuraThe Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama UniversityBackground: Chromium isotopes have been used to trace geochemical and cosmochemical processes in the past. However, the presence of multivalent Cr species has made it difficult to isolate Cr from geological samples, particularly for samples with a low Cr mass fraction.<br>
Results: Here, a simple three-step ion exchange chromatography procedure is presented to separate Cr from various sample matrices, ranging from ultramafic to felsic rocks. Throughout each of the column chromatography step, 1 mL of cation exchange resin AG50W-X8 (200–400 mesh) was used as the stationary phase and oxalic acid as a chelating agent, was used in addition to the inorganic acids. This method yielded high recoveries of Cr [93 ± 8% (2SD, N = 7)] regardless of the lithology. The total procedural blank of Cr was <0.5 ng. We also developed a double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS) technique that significantly reduced sample consumption to ∼20 ng of Cr per each measurement of mass-dependent 53Cr/52Cr.<br>
Significance: This study achieved a 2SD external precision of 0.02‰ for the analysis of NIST NBS3112a and of 0.01–0.07‰ for the geological samples. This study enabled high-precision Cr isotope analysis in geological samples with various matrix and Cr compositions using relatively small sample volumes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-283643652024Molecular Property, Manipulation, and Potential Use of Opn5 and Its Homologs168319ENKeitaSatoDepartment of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHideyoOhuchiDepartment of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAnimal opsin is a G-protein coupled receptor (GPCR) and binds retinal as a chromophore to form a photopigment. The Opsin 5 (Opn5) group within the animal opsin family comprises a diverse array of related proteins, such as Opn5m, a protein conserved across all vertebrate lineages including mammals, and other members like Opn5L1 and Opn5L2 found in non-mammalian vertebrate genomes, and Opn6 found in non-therian vertebrate genomes, along with Opn5 homologs present in invertebrates. Although these proteins collectively constitute a single clade within the molecular phylogenetic tree of animal opsins, they exhibit markedly distinct molecular characteristics in areas such as retinal binding properties, photoreaction, and G-protein coupling specificity. Based on their molecular features, they are believed to play a significant role in physiological functions. However, our understanding of their precise physiological functions and molecular characteristics is still developing and only partially realized. Furthermore, their unique molecular characteristics of Opn5-related proteins suggest a high potential for their use as optogenetic tools through more specialized manipulations. This review intends to encapsulate our current understanding of Opn5, discuss potential manipulations of its molecular attributes, and delve into its prospective utility in the burgeoning field of animal opsin optogenetics.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X3032024Relevance of complement immunity with brain fog in patients with long COVID236241ENHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaruhikoSunadaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuhiroNakanoDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiHondaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasanoriFurukawaClinical Laboratory, Okayama University HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction<br>
This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50).<br>
<br>
Methods<br>
This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors.<br>
<br>
Results<br>
Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33–5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04–2.66).<br>
<br>
Conclusions<br>
High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-36434102023Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors100573ENHidekiIkedaChiba Cancer Center, Research InstituteJojiNagasakiChiba Cancer Center, Research InstituteDaikiShimizuDivision of Thoracic Surgery, Chiba Cancer CenterYukiKatsuyaDepartment of Experimental Therapeutics, National Cancer Center HospitalHidehitoHorinouchiDepartment of Thoracic Oncology, National Cancer Center HospitalYukioHosomiDepartment of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalEtsukoTanjiChiba Cancer Center, Research InstituteTakekazuIwataDivision of Thoracic Surgery, Chiba Cancer CenterMakikoItamiDepartment of Surgical Pathology, Chiba Cancer CenterMasahitoKawazuChiba Cancer Center, Research InstituteYuichiroOheDepartment of Thoracic Oncology, National Cancer Center HospitalTakujiSuzukiDepartment of Respirology, Graduate School of Medicine, Chiba UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs).<br>
Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo.<br>
Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody.<br>
Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-50184102023Syncope and loss of consciousness after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: Prevalence and characteristics in long-term follow-up641649ENSaoriAsadaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomofumiMizunoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuroMasudaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiraUeokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakazuMiyamotoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKawadaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhiroNishiiDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Syncope is a significant prognostic factor in patients with Brugada syndrome (BrS). However, the risk of ventricular arrhythmia in patients with nonarrhythmic loss of consciousness (LOC) is similar to that in asymptomatic patients. LOC events after implantable cardioverter-defibrillator (ICD) implantation may provide insights into underlying causes of the initial LOC episode.<br>
Objective The purpose of this study was to examine LOC characteristics following ICD implantation.<br>
Methods We retrospectively analyzed 112 patients with BrS (mean age 47 years; 111 men) who were treated with an ICD. The patients were classified into 3 groups based on symptoms at implantation: asymptomatic (35 patients); LOC (46 patients); and ventricular tachyarrhythmia (VTA) (31 patients). We evaluated the incidence and cause of LOC during long-term follow-up after ICD implantation.<br>
Results During mean follow-up of 12.2 years, 41 patients (37%) experienced LOC after ICD implantation. Arrhythmic LOC occurred in 5 asymptomatic patients, 14 LOC patients, and 16 patients with VTA. Nonarrhythmic LOC, similar to the initial episode, occurred after ICD implantation in 6 patients with prior LOC (2 with neurally mediated syncope and 4 with epilepsy). Most epileptic patients experienced LOC during rest or sleeping, and did not show an abnormal encephalogram during initial evaluation of the LOC episodes.<br>
Conclusion After ICD implantation, 13% of patients had nonarrhythmic LOC similar to the initial episode. Accurate classification of LOC based on a detailed medical history is important for risk stratification, although distinguishing arrhythmic LOC from epilepsy-related LOC episodes can be challenging depending on the circumstances and characteristics of the LOC event.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1369-5274752023Continued mycovirus discovery expanding our understanding of virus lifestyles, symptom expression, and host defense102337ENYukiyoSatoInstitute for Plant Sciences, University of CologneNobuhiroSuzukiInstitute of Plant Science and Resources, Okayama UniversityHigh-throughput sequencing technologies have greatly expanded the RNA virome in general and have led to an exponential increase in new fungal viruses, also known as mycoviruses. Mycoviruses are omnipresent in fungi and usually induce symptomless infections. Some mycoviruses infecting fungi pathogenic to plants, insects, and mammals are known to modify host virulence positively and negatively and attract particular interests. In addition, fungal viruses continue to provide intriguing research materials and themes that lead to discoveries of peculiar viruses as infectious entities and insights into virus evolution and diversity. In this review, we outline the diversity and neolifestyle of recently discovered fungal RNA viruses, and phenotypic alterations induced by them. Furthermore, we discuss recent advances in research regarding the fungal antiviral defense and viral counterdefense, which are closely associated with host phenotype alterations. We hope that this article will enhance understanding of the interesting and growing fungal virology field.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0092-86741862023Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis41894203.e22ENNaotakaTsutsumiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZahraMasoumiYork Biomedical Research Institute, Department of Biology, University of YorkSophie C.JamesYork Biomedical Research Institute, Department of Biology, University of YorkJulie A.TuckerYork Biomedical Research Institute, Department of Biology, University of YorkHaukeWinkelmannDepartment of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabrück UniversityWilliamGreyYork Biomedical Research Institute, Department of Biology, University of YorkLora K.PictonDepartment of Molecular and Cellular Physiology, Stanford University School of MedicineLucieMossYork Biomedical Research Institute, Department of Biology, University of YorkSteven C.WilsonDepartment of Molecular and Cellular Physiology, Stanford University School of MedicineNathanael A.CaveneyDepartment of Molecular and Cellular Physiology, Stanford University School of MedicineKevin M.JudeDepartment of Molecular and Cellular Physiology, Stanford University School of MedicineCorneliusGatiDepartment of Structural Biology, Stanford University School of MedicineJacobPiehlerDepartment of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabrück UniversityIan S.HitchcockYork Biomedical Research Institute, Department of Biology, University of YorkK. ChristopherGarciaDepartment of Molecular and Cellular Physiology, Stanford University School of MedicineThrombopoietin (THPO or TPO) is an essential cytokine for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Here, we report the 3.4 Å resolution cryoelectron microscopy structure of the extracellular TPO-TPO receptor (TpoR or MPL) signaling complex, revealing the basis for homodimeric MPL activation and providing a structural rationalization for genetic loss-of-function thrombocytopenia mutations. The structure guided the engineering of TPO variants (TPOmod) with a spectrum of signaling activities, from neutral antagonists to partial- and super-agonists. Partial agonist TPOmod decoupled JAK/STAT from ERK/AKT/CREB activation, driving a bias for megakaryopoiesis and platelet production without causing significant HSC expansion in mice and showing superior maintenance of human HSCs in vitro. These data demonstrate the functional uncoupling of the two primary roles of TPO, highlighting the potential utility of TPOmod in hematology research and clinical HSC transplantation.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-5204152023Collapse-related traumatic intracranial hemorrhage following out-of-hospital cardiac arrest: A multicenter retrospective cohort study100418ENFumiyaInoueDepartment of Emergency Medicine, Hiroshima City HospitalTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshihisaIchibaDepartment of Emergency Medicine, Hiroshima City HospitalTakayukiOtaniDepartment of Emergency Medicine, Hiroshima City HospitalHiroshiNaitoDepartment of Emergency Medicine, Hiroshima City HospitalYoshinoriKosakiDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuyaMurakamiDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsuyoshiIidaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground: Sudden loss of consciousness as a result of cardiac arrest can cause severe traumatic head injury. Collapse-related traumatic intracranial hemorrhage (CRTIH) following out-of-hospital cardiac arrest (OHCA) may be linked to poor neurological outcomes; however, there is a paucity of data on this entity. This study aimed to investigate the frequency, characteristics, and outcomes of CRTIH following OHCA.<br>
Methods: Adult patients treated post-OHCA at 5 intensive care units who had head computed tomography (CT) scans were included in the study. CRTIH following OHCA was defined as a traumatic intracranial injury from collapse due to sudden loss of consciousness associated with OHCA. Patients with and without CRTIH were compared. The primary outcome assessed was the frequency of CRTIH following OHCA. Additionally, the clinical features, management, and consequences of CRTIH were analyzed descriptively.<br>
Results: CRTIH following OHCA was observed in 8 of 345 enrolled patients (2.3%). CRTIH was more frequent after collapse outside the home, from a standing position, or due to cardiac arrest with a cardiac etiology. Intracranial hematoma expansion on follow up CT was seen in 2 patients; both received anticoagulant therapy, and one required surgical evacuation. Three patients (37.5%) with CRTIH had favorable neurological outcomes 28 days after collapse.<br>
Conclusions: Despite its rare occurrence, physicians should pay special attention to CRTIH following OHCA during the post-resuscitation care period. Larger prospective studies are warranted to provide a more explicit picture of this clinical condition.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-5204152023Comparison of outcomes of out-of-hospital cardiac arrest patients: Emergency calls placed from mobile phones vs. landline phones100434ENTakeshiNishimuraDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasafumiSugaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiIshiharaDepartment of Emergency and Critical Care Medicine, Hyogo Emergency Medical CenterHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground: Until recently, calls to the emergency medical service (EMS) from landline phones, which display the caller’s exact location at the dispatch center, had been common. Since the use of mobile phones has become widespread, many emergency calls are now made from mobile phones. Differences in outcomes of out-of-hospital cardiac arrest (OHCA) patients for whom EMS was called from mobile versus landline phones has not yet been fully elucidated.<br>
Methods: We performed a retrospective, population-based analysis in Kobe, Japan to examine whether EMS calls from mobiles improved the prognosis of OHCA patients over EMS calls placed from landlines. The primary outcome was favorable neurological outcome, defined as Cerebral Performance Category (CPC) scores of 1 or 2 at discharge. Secondary outcomes were survival at one-month, survival at discharge, and time durations between call and EMS activities.<br>
Results: Of 4,231 OHCA cases, 2,194 cases (706 landline cases vs. 1,488 mobile cases) were included in this study. The percentages of favorable neurological outcomes were 0.7% (5/706) in the landline group and 3.8% (56/1,488) in the mobile group. Adjusted multivariable logistic regression revealed that favorable neurological outcomes (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.12–8.17, p = 0.03) were better in the mobile group, while one-month survival (OR 1.30, 95% CI 0.80–2.14, p = 0.29) was not significantly different. Bystander CPR was more frequently administered in the mobile group (landlines 61.3% vs. mobiles 68.4%, p < 0.01). Time durations between call to EMS dispatch (184.5 [IQR 157–220 s] vs. 205 [IQR 174–248 s], p < 0.01) and EMS arrival (476.5 [IQR 377–599 s] vs. 491 [IQR 407.5–611.5 s], p < 0.01) were shorter in the landline group.<br>
Conclusions: Although the landline caller location display system seems effective for shorter times between EMS call and EMS arrival, mobile phone use was associated with better neurological outcomes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-9145332023Epiretinal Membrane Impairs the Inner Retinal Layer in a Traction Force-Dependent Manner100312ENYukiKanzakiDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyoMatobaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShuheiKimuraDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMio M.HosokawaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeShiodeDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinichiroDoiDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTetsuroMoritaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySayumiKanzakiDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIppeiTakasuTakasu Eye ClinicAtsuhiroTanikawaDepartment of Ophthalmology, Fujita Health University Bantane HospitalYukiMorizaneDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM).<br>
Design: Nonrandomized, retrospective consecutive case series.<br>
Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled.<br>
Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction.<br>
Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens.<br>
Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = −0.657, P = 0.015; r = −0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P < 0.001; r = 0.210, P = 0.007, respectively). However, only the INL thickness progression rate was significantly correlated with the MDRF progression rate (r = 0.770, P < 0.001). On case stratification by localization of MDRF based on the ETDRS chart, in regions other than temporal regions, the INL thickness was significantly greater in regions with MDRF than in other regions. The MDRF significantly correlated with α-SMA expression in the ERM specimens (r = 0.555, P = 0.009).<br>
Conclusions: The findings suggest that ERM impairs the inner retinal layer in a traction force-dependent manner.<br>
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-9145332023Quantitative Analyses of Retinal Traction Force and Metamorphopsia in Lamellar Macular Hole and Related Diseases100305ENMaiMinoDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyoMatobaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiKanzakiDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShuheiKimuraDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMio M.HosokawaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeShiodeDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTetsuroMoritaDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiMorizaneDepartment of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityPurpose: To investigate the involvement of retinal traction in the pathogenesis of lamellar macular hole (LMH) and related diseases based on OCT–based consensus definition. <br>
Design: Retrospective, observational study. <br>
Participants: Seventy-two eyes with LMH, epiretinal membrane foveoschisis (ERM-FS), or macular pseudohole (MPH). <br>
Methods: To quantitatively evaluate the involvement and strength of retinal traction in their pathogenesis, retinal folds were visualized with en face OCT imaging, and the maximum depth of the parafoveal retinal folds (MDRF) was measured. Metamorphopsia was quantified by measuring the minimum visual angle of dotted lines needed to cause it to disappear using M-CHARTS (Inami). <br>
Main Outcome Measures: Maximum depth of retinal folds and M-CHARTS scores. <br>
Results: Of the 72 eyes, 26 were classified as having LMH, 25 as having ERM-FS, and 21 as having MPH. Parafoveal retinal folds were observed in 7 (26.9%) eyes with LMH, 25 (100%) with ERM-FS, and 21 (100%) with MPH. The MDRF (7.5 ± 17.6 μm) was significantly smaller in LMH than in ERM-FS (86.3 ± 31.4 μm) and MPH (74.5 ± 24.6 μm) (both P < 0.001), whereas no significant difference in MDRF between MPH and ERM-FS was observed (P = 0.43). A significant positive correlation between MDRF and M-CHARTS scores was observed in ERM-FS and MPH (P = 0.008 and 0.040, respectively) but not in LMH (P = 0.073). <br>
Conclusions: Retinal traction was significantly weaker in the LMH group than in the ERM-FS and MPH groups. The MDRF was significantly associated with the degree of metamorphopsia in the ERM-FS and MPH groups. These results provide insights into the diseases’ pathophysiology and treatment strategy. <br>
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0531-55651802023Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival112270ENToshiyukiAokageDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasumiIketaniBiological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and GerontologyMizukiSeyaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYingMengDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiAgetaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIkurohOhsawaBiological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and GerontologyIntroduction: With the global population aging, there is an increased prevalence of sepsis among the elderly, a demographic particularly susceptible to inflammation. This study aimed to evaluate the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in attenuating inflammation specifically in the lungs and liver, and age-associated molecular markers in aged mice.<br>
Methods: Male mice aged 21 to 23 months, representative of the human elderly population, were subjected to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). The mice were allocated into eight groups to examine the effects of varying durations and concentrations of hydrogen gas inhalation: control, saline without hydrogen, saline with 24-hour 2 % hydrogen, LPS without hydrogen, LPS with 24-hour 2 % hydrogen, LPS with 6-hour 2 % hydrogen, LPS with 1-hour 2 % hydrogen, and LPS with 24-hour 1 % hydrogen. Parameters assessed included survival rate, activity level, inflammatory biomarkers, and organ injury.<br>
Results: Extended administration of hydrogen gas specifically at a 2 % concentration for 24 h led to a favorable prognosis in the aged mice by reducing mRNA expression of inflammatory biomarkers in lung and liver tissue, mitigating lung injury, and diminishing the expression of the senescence-associated protein p21. Moreover, hydrogen gas inhalation selectively ameliorated senescence-related markers in lung tissue, including C-X-C motif chemokine 2, metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not alleviate LPS-induced liver injury under the conditions tested.<br>
Conclusion: The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1368-83751422023EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma106433ENKokiUmemoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKishoOnoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriEguchiDepartment of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHotakaKawaiDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomoyaNakamuraDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTatsuoOgawaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKunihiroYoshidaDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidekaKanemotoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKoheiSatoDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoichiObataDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShojiRyumonDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokazuYutoriDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaokiKataseDepartment of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki UniversityTatsuoOkuiDepartment of Oral and Maxillofacial Surgery, Shimane University Faculty of MedicineHitoshiNagatsukaDepartment of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiroIbaragiDepartment of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjectives: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance.<br>
Materials and methods: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS).<br>
Results: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner.<br>
Conclusion: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1751-73111772023Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves100873ENS.KatsumataGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityY.HayashiShiga Prefectural Livestock Production Technology Promotion CenterK.OishiDepartment of Applied Biosciences, Graduate School of Agriculture, Kyoto UniversityT.TsukaharaKyoto Institute of Nutrition and PathologyR.InoueDepartment of Applied Biological Sciences, Faculty of Agriculture, Setsunan UniversityA.ObataShiga Prefectural Livestock Production Technology Promotion CenterH.HirookaDepartment of Applied Biosciences, Graduate School of Agriculture, Kyoto UniversityH.KumagaiDepartment of Applied Biosciences, Graduate School of Agriculture, Kyoto UniversityLiquefied sake lees, a by-product of Japanese sake, is rich in Saccharomyces cerevisiae, proteins, and prebiotics derived from rice and yeast. Previous studies have reported that Saccharomyces cerevisiae fermentation products improved the health, growth, and faecal characteristics of preweaning calves. This study investigated the effects of adding liquefied sake lees to milk replacer on the growth performance, faecal characteristics, and blood metabolites of preweaning Japanese Black calves from 6 to 90 days of age. Twenty-four Japanese Black calves at 6 days of age were randomly assigned to one of three treatments: No liquefied sake lees (C, n = 8), 100 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (LS, n = 8), and 200 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (HS, n = 8). The intake of milk replacer and calf starter, as well as, the average daily gain did not differ between the treatments. The number of days counted with faecal score 1 in LS was higher than in HS (P < 0.05), while the number of days with diarrhoea medication in LS and C was lower than HS (P < 0.05). The faecal n-butyric acid concentration tended to be higher in LS compared to C (P = 0.060). The alpha diversity index (Chao1) was higher in HS than in C and LS at 90 days of age (P < 0.05). The principal coordinate analysis (PCoA) using weighted UniFrac distance showed that the bacterial community structures in faeces among the treatments at 90 days of age were significantly different (P < 0.05). The plasma β-hydroxybutyric acid concentration, an indicator of rumen development, was higher for LS than in C throughout the experiment (P < 0.05). These results suggested that adding liquefied sake lees up to 100 g/d (on a fresh matter basis) might promote rumen development in preweaning Japanese Black calves.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071382022Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization101669ENMasatakaTaokaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalNoriyukiUmakoshiDepartment of Radiology, Okayama University HospitalKiichiroNinomiyaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalYukaKatoCenter for Innovative Clinical Medicine, Okayama University HospitalMasanoriFujiiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalToshioKuboCenter for Clinical Oncology, Okayama University HospitalEikiIchiharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKadoakiOhashiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalKatsuyukiHottaCenter for Innovative Clinical Medicine, Okayama University HospitalMasahiroTabataCenter for Clinical Oncology, Okayama University HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitalA 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1015-958446102023Robotic surgery for congenital biliary dilatation using the scope switch technique (with video)43994402ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTomokazuFujiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTechnique: Minimally invasive congenital biliary dilatation (CBD) surgery is technically demanding. However, few studies have reported surgical approaches of robotic surgery for CBD. This report presents robotic CBD surgery using a scope-switch technique. Our robotic surgery technique for CBD consisted of four steps: step 1, Kocher's maneuver; step 2, dissection of the hepatoduodenal ligament using the scope switch technique; step 3, preparation for the Roux-en-Y loop; and step 4, hepaticojejunostomy. <br>
Results: The scope switch technique can provide different surgical approaches for dissecting the bile duct, including anterior approach by the standard position and right approach by the scope switch position. When approaching the ventral and left side of the bile duct, anterior approach with the standard position is suitable. In contrast, the lateral view by the scope switch position is preferable for approaching the bile duct laterally and dorsally. Using this technique, the dilated bile duct can be dissected circumferentially from four directions: anterior, medial, lateral, and posterior. Thereafter, complete resection of the choledochal cyst can be achieved. <br>
Conclusions: The scope switch technique in robotic surgery for CBD can be useful for dissecting around the bile duct with different surgical views, leading to the complete resection of the choledochal cyst.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071452023Mycobacterium shinjukuense infection successfully treated with clarithromycin, rifampicin, and ethambutol101894ENKayoNakamuraDepartment of Medicine, Japanese Red Cross Society Himeji HospitalEtsukoMurakamiDepartment of Medicine, Japanese Red Cross Society Himeji HospitalDaizoKishinoDepartment of Medicine, Japanese Red Cross Society Himeji HospitalShukoMashimoDepartment of Medicine, Japanese Red Cross Society Himeji HospitalYusukeKuriokaDepartment of Medicine, Japanese Red Cross Society Himeji HospitalYusakuShibataDepartment of Medicine, Japanese Red Cross Society Himeji HospitalArihikoTaniguchiDepartment of Allergy and Respiratory Medicine, Okayama University HospitalHisaoHigoDepartment of Allergy and Respiratory Medicine, Okayama University HospitalYasushiHiramatsuDepartment of Medicine, Japanese Red Cross Society Himeji HospitalYoshinobuMaedaDepartment of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Allergy and Respiratory Medicine, Okayama University HospitalWe present the case of a 59-year-old woman diagnosed with Mycobacterium shinjukuense infection using mass spectrometry of bronchioalveolar lavage fluid. We initiated treatment with clarithromycin, rifampicin, and ethambutol based on the results of drug susceptibility testing, which improved lung opacities. Most previous cases were treated with the standard regimen for Mycobacterium tuberculosis. However, our regimen may provide a therapeutic option for this rare nontuberculous Mycobacterium infection.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama187940681452023Significance of the comprehensive geriatric assessment in the administration of chemotherapy to older adults with cancer: Recommendations by the Japanese Geriatric Oncology Guideline Committee101485ENKiichiroNinomiyaCenter for Comprehensive Genomic Medicine, Okayama University HospitalDaisukeInoueDepartment of Obstetrics and Gynecology, University of FukuiKenSugimotoDepartment of General Geriatric Medicine, Kawasaki Medical SchoolChieTanakaDepartment of Gastroenterological Surgery, Nagoya University Graduate School of MedicineKeikoMurofushiDivision of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalToruOkuyamaDepartment of Psychiatry / Palliative Care Center, Nagoya City University West Medical CenterShigeakiWatanukiNational Center for Global Health and Medicine, National College of NursingChiyo K.ImamuraAdvanced Cancer Translational Research Institute, Showa UniversityDaisukeSakaiDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of MedicineNaomiSakuraiCancer Solutions Co.,LtdKiyotakaWatanabeDivision of Medical Oncology, Department of Medicine, School of Medicine, Teikyo UniversityKazuoTamuraNPO Clinical Hematology/Oncology Treatment Study GroupToshiakiSaekiBreast Oncology Service, Saitama Medical University International Medical CenterHiroshiIshiguroBreast Oncology Service, Saitama Medical University International Medical CenterIntroduction: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved.<br>
Materials and Methods: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.<br>
Results: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions.<br>
Discussion: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-5766932023Transmural necrosis of the ascending colon secondary to traumatic hemorrhagic shock: A case report102646ENKenjiAoshimaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesIntroduction: Acute mesenteric ischemia is caused by a severe reduction in blood flow to the intestine, eventually resulting in non-occlusive mesenteric ischemia, and less frequently, bowel necrosis, which is associated with high mortality.<br>
Case presentation: We report a 10-year-old boy with no past medical history with necrosis of the ascending colon after resuscitation from hemorrhagic shock due to femoral vein injury caused by a bicycle handlebar injury. Contrast-enhanced computed tomography demonstrated hypodense thickening of the ascending colon wall and intrahepatic portal gas. Exploratory laparoscopy demonstrated necrosis of the ascending colon and paralysis of the intestines.<br>
Conclusion: Colonic necrosis secondary to hemorrhagic shock in children without evidence of pre-existing cardiovascular disease is extremely uncommon. Lack of familiarity with this condition may cause serious complications. Clinicians must be aware of this disease to promptly diagnose and aggressively treat the condition early.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0039-606017422023Hydrogen inhalation attenuates lung contusion after blunt chest trauma in mice343349ENKoheiAgetaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyukiAokageDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizukiSeyaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYingMengDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirotsuguYamamotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiTsukaharaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Lung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion.<br>
Methods: Inbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion.<br>
Results: Histopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation.<br>
Conclusion: Hydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-4569922023Oncologic and Safety Outcomes for Endoscopic Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An Updated Systematic Review and Meta-analysis236240ENTatsushiKawadaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEkaterinaLaukhtinaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFahadQuhalDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaTakafumiYanagisawaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaPawelRajwaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaMaximilianPallaufDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaMarkusvon DeimlingDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaAlbertoBianchiDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaBenjaminPradereDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaHarunFajkovicDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaDmitryEnikeevInstitute for Urology and Reproductive Health, Sechenov UniversityPaoloGonteroDivision of Urology, Molinette Hospital, University of Studies of TorinoMorganRouprêtDepartment of Urology, Sorbonne Université, GRC n°5, Predictive Onco-urology, AP-HP, Pitié-Salpêtrière HospitalThomasSeisenDivision of Urology, Department of Special Surgery, The University of JordanMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShahrokh F.ShariatDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaWe systematically reviewed the literature and summarized oncologic and safety outcomes for endoscopic management (EM) compared to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). Studies comparing oncologic and/or safety results for EM versus RNU in patients with UTUC were included in our review. Overall, 13 studies met the criteria, and five studies were included in a meta-analysis using adjusted hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). EM was associated similar OS (HR 1.27, 95% confidence interval [CI] 0.75–2.16), CSS (HR 1.37, 95% CI 0.99–1.91), and BRFS (HR 0.98, 95% CI 0.61–1.55) to RNU, while 28–85% of patients treated with EM experienced upper tract recurrence across the studies. EM required more interventions with a higher cumulative risk of complications and lower likelihood of renal preservation. In summary, EM for low-grade UTUC had comparable survival outcomes to RNU at the cost of higher local recurrence rates resulting in a need for long-term rigorous surveillance and repeated interventions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1477-8939522023Shigellosis in Southeast Asia: A systematic review and meta-analysis102554ENBasilua AndreMuzemboGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiKitaharaGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDebmalyaMitraCollaborative Research Centre of Okayama University for Infectious Diseases in India at ICMR-NICEDAyumuOhnoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJanukaKhatiwadaSocial Work InstituteShantaDuttaDivision of Bacteriology, ICMR-National Institute of Cholera and Enteric DiseasesShin-IchiMiyoshiGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Southeast Asia is attractive for tourism. Unfortunately, travelers to this region are at risk of becoming infected with Shigella. We conducted a meta-analysis to provide updates on Shigella prevalence in Southeast Asia, along with their serogroups and serotypes.<br>
Methods: We conducted a systematic search using PubMed, EMBASE, and Web of Science for peer-reviewed studies from 2000 to November 2022. We selected studies that detected Shigella in stools by culture or polymerase chain reaction (PCR). Two reviewers extracted the data using a standardized form and performed quality assessments using the Joanna Briggs Institute checklist. The random effects model was used to estimate the pooled prevalence of Shigella.<br>
Results: During our search, we identified 4376 studies. 29 studies (from six Southeast Asian countries) were included in the systematic review, 21 each in the meta-analysis of the prevalence of Shigella (Sample size: 109545) and the prevalence of Shigella serogroups.<br>
The pooled prevalence of Shigella was 4% (95% CI: 4–5%) among diarrhea cases. Shigella sonnei was the most abundant serogroup in Thailand (74%) and Vietnam (57%), whereas Shigella flexneri was dominant in Indonesia (72%) and Cambodia (71%). Shigella dysenteriae and Shigella boydii were uncommon (pooled prevalence of 1% each). The pooled prevalence of Shigella was 5% (95% CI: 4–6%) in children aged <5 years. The pooled prevalence showed a decreasing trend comparing data collected between 2000–2013 (5%; 95% CI: 4–6%) and between 2014–2022 (3%; 95% CI: 2–4%). Shigella prevalence was 6% in studies that included participants with mixed pathogens versus 3% in those without. Shigella flexneri serotype 2a was the most frequently isolated (33%), followed by 3a (21%), 1b (10%), 2b (3%), and 6 (3%).<br>
Conclusions: This study provides compelling evidence for the development of effective Shigella vaccines for residents of endemic regions and travellers to these areas.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X29952023Actin-rich lamellipodia-like protrusions contribute to the integrity of epithelial cell-cell junctions104571ENYosukeSenjuResearch Institute for Interdisciplinary Science (RIIS), Okayama UniversityToibaMushtaqHelsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of HelsinkiHelenaVihinenHelsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of HelsinkiAkiManninenFaculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of OuluJuhaSaarikangasHelsinki Institute of Life Science (HiLIFE), University of HelsinkiKatharinaVenHelsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of HelsinkiUlrikeEngelNikon Imaging Center and Centre for Organismal Studies, Heidelberg UniversityMarkkuVarjosaloHelsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of HelsinkiEijaJokitaloHelsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of HelsinkiPekkaLappalainenHelsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of HelsinkiMetastasis-suppressor 1 (MTSS1) is a membrane-interacting scaffolding protein that regulates the integrity of epithelial cell-cell junctions and functions as a tumor suppressor in a wide range of carcinomas. MTSS1 binds phosphoinositide-rich membranes through its I-BAR domain and is capable of sensing and generating negative membrane curvature in vitro. However, the mechanisms by which MTSS1 localizes to inter-cellular junctions in epithelial cells and contributes to their integrity and maintenance have remained elusive. By carrying out EM and live-cell imaging on cultured Madin-Darby canine kidney cell monolayers, we provide evidence that adherens junctions of epithelial cells harbor lamellipodia-like, dynamic actin-driven membrane folds, which exhibit high negative membrane curvature at their distal edges. BioID proteomics and imaging experiments demonstrated that MTSS1 associates with an Arp2/3 complex activator, the WAVE-2 complex, in dynamic actin-rich protrusions at cell-cell junctions. Inhibi-tion of Arp2/3 or WAVE-2 suppressed actin filament assembly at adherens junctions, decreased the dynamics of junctional membrane protrusions, and led to defects in epithelial integ-rity. Together, these results support a model in which membrane-associated MTSS1, together with the WAVE-2 and Arp2/3 complexes, promotes the formation of dynamic lamellipodia-like actin protrusions that contribute to the integrity of cell-cell junctions in epithelial monolayers.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440942023Diagnostic value of circulating microRNA-21 in chronic lung allograft dysfunction after bilateral cadaveric and living-donor lobar lung transplantatione14903ENToshioShiotaniOrgan Transplant Center, Okayama University HospitalSeiichiroSugimotoOrgan Transplant Center, Okayama University HospitalYasuakiTomiokaOrgan Transplant Center, Okayama University HospitalHaruchikaYamamotoDepartment of General Thoracic Surgery, Okayama University HospitalShinTanakaOrgan Transplant Center, Okayama University HospitalKentarohMiyoshiDepartment of General Thoracic Surgery, Okayama University HospitalKenSuzawaDepartment of General Thoracic Surgery, Okayama University HospitalKazuhikoShienDepartment of General Thoracic Surgery, Okayama University HospitalHiromasaYamamotoDepartment of General Thoracic Surgery, Okayama University HospitalMikioOkazakiDepartment of General Thoracic Surgery, Okayama University HospitalShinichiToyookaDepartment of General Thoracic Surgery, Okayama University HospitalBackground: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT). <br>
Methods: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD. <br>
Results: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P < 0.05). A receiver operating characteristic curve analysis of the performance of miR-21 levels in the diagnosis of CLAD yielded an area under the curve of 0.89. <br>
Conclusion: Circulating miR-21 appears to be of potential value in diagnosing CLAD after bilateral LT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409482023The dataset of de novo assembly and inferred functional annotation of the transcriptome of Heterosigma akashiwo, a bloom-forming, cosmopolitan raphidophyte109071ENMasanaoSatoDivision of Applied Bioscience, Graduate School of Agriculture, Hokkaido UniversityMasahideSekiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoYutakaSuzukiDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoShokoUekiInstitute of Plant Science and Resources, Okayama UniversityHeterosigma akashiwo is a eukaryotic, cosmopolitan, and uni-cellular alga (class: Raphidophyceae), and produces fish -killing blooms. There is a substantial scientific and practical interest in its ecophysiological characteristics that determine bloom dynamics and its adaptation to broad climate zones. A well-annotated genomic/genetic sequence information en-ables researchers to characterize organisms using modern molecular technology. In the present study, we conducted H. akashiwo RNA sequencing, a de novo transcriptome assem-bly of 84,693,530 high-quality deduplicated short-read se-quences. <br>
Obtained RNA reads were assembled by Trinity assembler and 144,777 contigs were identified with N 50 values of 1085. Total 60,877 open reading frames with the length of 150 bp or greater were predicted. For further analy-ses, top Gene Ontology terms, pfam hits, and blast hits were annotated for all the predicted genes. The raw data were deposited in the NCBI SRA database (BioProject PR - JDB6241 and PRJDB15108), and the assemblies are available in NCBI TSA database (ICRV01). The annotation information can be obtained in Dryad and can be accessed via doi: 10.5061/dryad.m0cfxpp56.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-522316632023When to Intervene the Pulmonary Artery: Importance of Anatomical Assessment in the Diagnosis of Pulmonary Artery Coarctation926932ENEiriKisamoriDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalYasuhiroKotaniDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalHiroyukiSuzukiDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalJunkoKobayashiDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalTakuyaKawabataDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalYosukeKurokoDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalShingoKasaharaDepartment of Cardiovascular Surgery, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University and Okayama University HospitalObjective: Pulmonary artery coarctation (PACoA) is a major problem that increases the frequency of intervention. However, there is little evidence regarding the prediction of PACoA development.<br>
Methods: A retrospective chart review was performed on 42 patients who underwent modified Blalock-Taussig shunt and preoperative contrast-enhanced computed tomography. An uneven PA branching was defined as an abnormal ductus arteriosus connection to the left PA distal to the PA branching on contrast-enhanced computed tomography.<br>
Results: Nineteen (45.2%) of 42 patients were diagnosed with PACoA. The median diameters of the ductus on the aorta and PA sides were 4.1 mm and 3.6 mm in the PACoA group and 3.6 mm and 2.9 mm in the non-PACoA group, respectively (P = .07 and .28, respectively). Tortuous ductus was recognized in 7 (36.8%) patients in the PACoA group and 14 (60.8%) patients in the non-PACoA group (P = .12). PACoA was associated with pulmonary atresia (16 patients [84.2%] in the PACoA group and 12 patients [52.1%] in the non-PACoA group) (P = .02). All 19 patients had uneven PA branching in the PACoA group, whereas 5 of 23 (21.7%) patients had uneven PA branching in the non-PACoA group (P < .001).<br>
Conclusions: Uneven PA branching rather than the ductus arteriosus size was strongly associated with PACoA development; therefore, morphologic assessment by contrast-enhanced computed tomography should be considered in patients with pulmonary atresia.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-6316252023Patient-specific respiratory motion management using lung tumors vs fiducial markers for real-time tumor-tracking stereotactic body radiotherapy100405ENYoshinoriTanabeFaculty of Medicine, Graduate School of Health Sciences, Okayama UniversityMichiruKiritaniFacilty of Health Sciences, Okayama University Medical SchoolTomomiDeguchiFacilty of Health Sciences, Okayama University Medical SchoolNanamiHiraFacilty of Health Sciences, Okayama University Medical SchoolSyoutaTomimotoFacilty of Health Sciences, Okayama University Medical SchoolBackground and purpose: In real-time lung tumor-tracking stereotactic body radiotherapy (SBRT), tracking accuracy is related to radiotherapy efficacy. This study aimed to evaluate the respiratory movement relationship between a lung tumor and a fiducial marker position in each direction using four-dimensional (4D) computed tomography (CT) images.<br>
Materials and methods: A series of 31 patients with a fiducial marker for lung SBRT was retrospectively analyzed using 4DCT. In the upper (UG) and middle and lower lobe groups (MLG), the cross-correlation coefficients of respiratory movement between the lung tumor and fiducial marker position in four directions (anterior–posterior, left–right, superior–inferior [SI], and three-dimensional [3D]) were calculated for each gating window (≤1, ≤2, and ≤ 3 mm). Subsequently, the proportions of phase numbers in unplanned irradiation (with lung tumors outside the gating window and fiducial markers inside the gating window) were calculated for each gating window.<br>
Results: In the SI and 3D directions, the cross-correlation coefficients were significantly different between UG (mean r = 0.59, 0.63, respectively) and MLG (mean r = 0.95, 0.97, respectively). In both the groups, the proportions of phase numbers in unplanned irradiation were 11 %, 28 %, and 63 % for the ≤ 1-, ≤2-, and ≤ 3-mm gating windows, respectively.<br>
Conclusions: Compared with MLG, fiducial markers for UG have low cross-correlation coefficients between the lung tumor and the fiducial marker position. Using 4DCT to assess the risk of unplanned irradiation in a gating window setting and selecting a high cross-correlation coefficient fiducial marker in advance are important for accurate treatment using lung SBRT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama009042951702022Simplified PADUA REnal (SPARE) Nephrometry System can Describe the Surgical Difficulty of Renal Masses With High Accuracy Even Without 3D Renal Models132138ENTomofumiWatanabeDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakuyaSadahiraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakanoriSekitoDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiMaruyamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiEdamuraDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasuyukiKobayashiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotooArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjective: To evaluate whether a 2-dimensional(2D) model describes the surgical difficulty of a renal mass accurately comparable to that obtained using a 3D model with the Simplified PADUA REnal nephrometry system (SPARE).<br>
Methods: A total of 100 patients underwent RAPN in our hospital between October 2018 and May 2021. We excluded patients with CT images inappropriate for evaluation or for construction of 3D models, patients with multiple tumors, and those who underwent preoperative transcatheter arterial embolization. We conducted a retrospective analysis of the remaining patients using SPARE predictions from CT images (2D-SPARE) and SPARE predictions from 3D models (3D-SPARE). We evaluated the difference between the 2 nephrometry scores and compared them by their ability to predict the achievement of the desired surgical outcome: absence of positive margins, absence of ischemia, and absence of significant complications.<br>
Results: A total of 87 patients were included in this study. Total score, and risk categorization using 3D-SPARE was significantly different from those using 2D-SPARE (P <.05), but in their areas under the curve (AUC), the scores and categorizations were not significantly different (score, 0.763 vs 0.742; P = .501; categorization, 0.711 vs 0.701; P = .755).<br>
Conclusion: The SPARE system can describe the surgical difficulty of renal masses with high accuracy even without the use of 3D renal models.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0163-44538542022Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people436480ENHideharuHagiyaDepartment of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakaoHikitaOffice of Innovative Medicine, Organization for Research Strategy and Development, Okayama UniversityTomohiroHabuDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakiAsadaDepartments of Medical Education, Kurashiki Central HospitalTakashiYorifujiDepartment of Epidemiology, Dentistry and Pharmaceutical Sciences, Graduate School of MedicineShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasanoriNakayamaOffice of Innovative Medicine, Organization for Research Strategy and Development, Okayama UniversityNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama26662507152022Physiologic biventricular repair in a patient with unrepaired adult congenital heart disease with severe cyanosis220223ENHiroyukiSuzukiDepartment of Cardiovascular Surgery, Okayama UniversityYosukeKurokoDepartment of Cardiovascular Surgery, Okayama UniversityYasuhiroKotaniDepartment of Cardiovascular Surgery, Okayama UniversityShingoKasaharaDepartment of Cardiovascular Surgery, Okayama UniversityNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1036-73143642023Frequency, associated factors, and associated outcomes of dysphagia following sepsis521527ENTakashiHongoOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster MedicineTetsuyaYumotoOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster MedicineHiromichiNaitoOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster MedicineToshifumiFujiwaraOkayama Saiseikai General Hospital, Emergency DepartmentJunKondoOkayama Saiseikai General Hospital, Department of Internal MedicineSatoshiNozakiOkayama Saiseikai General Hospital, Emergency DepartmentAtsunoriNakaoOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster MedicineBackground: Identifying dysphagia as a potential complication of sepsis may improve swallowing function and survival while decreasing hospital length of stay.<br>
Objectives: Our goal was to determine the frequency of dysphagia in sepsis survivors on the 7th day after admission, as well as their associated factors and outcomes.<br>
Methods: This single-centre, retrospective, observational study analysed data from sepsis survivors admitted to Okayama Saiseikai General Hospital from 2018 to 2019. Participants with sepsis were assigned to one of two study groups based on the presence or absence of dysphagia using the criterion of Functional Oral Intake Scale score <5 on the 7th day after admission. We used multivariate logistic regression to determine factors independently associated with dysphagia on the 7th day after admission. Multivariate logistic regression was also used to determine associations between groups and outcomes, including dysphagia on hospital discharge, direct discharge home (discharge of patients directly to their home), and total dependency (Barthel Index score ≤20) on hospital discharge.<br>
Results: One hundred one patients met the study inclusion criteria, 55 with dysphagia and 46 without dysphagia. Fasting period (adjusted odds ratio [AOR]: 1.31, 95% confidence interval [CI]: 1.07–1.59) and enteral tube feeding (AOR: 8.56, 95% CI: 1.95–37.5) were independently associated with the presence of dysphagia on the 7th day after admission. Dysphagia on the 7th day after admission was associated with dysphagia on hospital discharge (AOR: 46.0, 95%, CI: 7.90–268.3), a lower chance of direct discharge home (AOR: 0.03, 95% CI: 0.01–0.15), and a higher incidence of total dependency (AOR: 9.30, 95% CI: 2.68–32.2).<br>
Conclusions: We found that dysphagia was commonly encountered post sepsis. Fasting period and enteral tube feeding were independently associated with dysphagia on the 7th day after admission. Dysphagia on the 7th day after admission was also associated with dysphagia on hospital discharge, nondirect discharge home, and dependency in activities of daily living at the time of hospital discharge.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-38004642022Quantifying the GCM-related uncertainty for climate change impact assessment of rainfed rice production in Cambodia by a combined hydrologic - rice growth model109815ENK.TsujimotoGraduate School of Environmental and Life Science, Okayama UniversityN.KuriyaFaculty of Environmental Science and Technology, Okayama UniversityT.OhtaAssistance Unit for Research and Engineering Development (U-PRIMO)K.HommaGraduate School of Agricultural Science, Tohoku UniversityM.SoImMinistry of Water Resources and Meteorology (MOWRAM) of CambodiaThe effects of climate change on agriculture are a major concern for global food security. In this study, the impacts of climate change on rainfed rice production in the granary of Cambodia were examined on a basin scale by developing and applying a combined model consisting of a crop model and a basin-scale distributed hydrological model. The response of rice production to soil-water availability was simulated for past (1981–2000) and future (2041–2060, 2081–2100) periods. From 34 general circulation models (GCMs) that participated in the Coupled Model Intercomparison Project Phase 5 (CMIP5), 5 GCMs were selected by evaluating monthly rainfall in the past. Although annual rainfall was projected to increase by all five selected GCMs, notable decreases in rainfed rice production were projected with 3 GCMs, while small changes were projected with the other 2 GCMs. The main factor restricting future rice production was soil water availability, brought by the projected change in the seasonal distribution of rainfall and the projected more severe dry spells in the early monsoon season. The results suggest the importance of the selection and bias correction of GCMs to force rice crop models and of the simulation of soil water flow on a basin scale for the assessment of rain-fed rice production. In particular, improvements in projections of rainfall amounts over shorter periods rather than annual or seasonal periods, which fit within the time scales of rice plant growth, were suggested to be important.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22135766772022A case of esophageal atresia complicated by a right-sided aortic arch with right ductus arteriosus and inferior vena cava interruption with hemiazygos continuation102167ENTerutakaTanimotoDepartment of Pediatric Surgery, Okayama University HospitalTakuoNodaDepartment of Pediatric Surgery, Okayama University HospitalHiroshiNousoDepartment of Pediatric Surgery, Okayama University HospitalYukinoriMiyataDepartment of Pediatric Surgery, Okayama University HospitalDuring the repair of esophageal atresia with tracheoesophageal fistula (EA/TEF), cardiovascular malformations occasionally create a technical challenge. We report a novel case of a 4-day-old girl with EA/TEF and multiple cardiovascular malformations, including right-sided aortic arch (RAA), right ductus arteriosus (RDA), single ventricle with single atrium, common atrioventricular valve, pulmonary atresia, bilateral superior vena cava, and interruption of the inferior vena cava (IVC) with hemiazygos continuation. In this case, a right-sided approach would require the mobilization of the RAA and RDA, which were supplying the pulmonary blood flow due to pulmonary atresia. Alternatively, the left-sided approach would require the mobilization of the hemiazygos vein, which was essential for venous return from the lower body due to IVC interruption. We performed the less intrusive left-sided approach, and the postoperative course was uneventful. Right-sided EA/TEF repair should be avoided because RDA spasm or injury caused by RAA mobilization would be fatal. In cases of interrupted IVC with azygos or hemiazygos vein continuation, care must be taken not to ligate these vessels or block the venous return. Preoperative evaluation is important to prevent complications in such complicated cases. If sufficient information is not available, the left-sided approach may be preferred.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1083-351X298122022Crystal structures of photosystem II from a cyanobacterium expressing psbA2 in comparison to psbA3 reveal differences in the D1 subunit102668ENYoshikiNakajimaResearch Institute for Interdisciplinary Science, Okayama UniversityNatsumiUgai-AmoGraduate School of Natural Science and Technology, Okayama UniversityNaokiToneGraduate School of Natural Science and Technology, Okayama UniversityAkikoNakagawaProteo-Science Research Center, Ehime UniversityMasakoIwaiGraduate School and College of Arts and Sciences, The University of TokyoMasahikoIkeuchiGraduate School and College of Arts and Sciences, The University of TokyoMiwaSugiuraProteo-Science Research Center, Ehime UniversityMichihiroSugaResearch Institute for Interdisciplinary Science, Okayama UniversityShenJian-RenResearch Institute for Interdisciplinary Science, Okayama UniversityThree psbA genes (psbA1, psbA2, and psbA3) encoding the D1 subunit of photosystem II (PSII) are present in the ther-mophilic cyanobacterium Thermosynechococcus elongatus and are expressed differently in response to changes in the growth environment. To clarify the functional differences of the D1 protein expressed from these psbA genes, PSII dimers from two strains, each expressing only one psbA gene (psbA2 or psbA3), were crystallized, and we analyzed their structures at resolu-tions comparable to previously studied PsbA1-PSII. Our results showed that the hydrogen bond between pheophytin/D1 (PheoD1) and D1-130 became stronger in PsbA2-and PsbA3-PSII due to change of Gln to Glu, which partially explains the increase in the redox potential of PheoD1 observed in PsbA3. In PsbA2, one hydrogen bond was lost in PheoD1 due to the change of D1-Y147F, which may explain the decrease in stability of PheoD1 in PsbA2. Two water molecules in the Cl-1 channel were lost in PsbA2 due to the change of D1-P173M, leading to the narrowing of the channel, which may explain the lower efficiency of the S-state transition beyond S2 in PsbA2-PSII. In PsbA3-PSII, a hydrogen bond between D1-Ser270 and a sulfoquinovosyl-diacylglycerol molecule near QB dis-appeared due to the change of D1-Ser270 in PsbA1 and PsbA2 to D1-Ala270. This may result in an easier exchange of bound QB with free plastoquinone, hence an enhancement of oxygen evolution in PsbA3-PSII due to its high QB exchange efficiency. These results provide a structural basis for further functional examination of the three PsbA variants.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409442022The dataset of Japanese patents and patents' holding firms in green vehicle powertrains field108524ENJiamingJiangGraduate School of Humanities and Social Science, Okayama UniversityKensukeBabaCyber-Physical Engineering Informatics Research Core, Okayama UniversityYuZhaoSchool of Management, Department of Management, Tokyo University of ScienceJunshiFengGraduate School of Humanities and Social Science, Okayama UniversitySouKumagaiDepartment of Electrical and Communication Engineering, Faculty of Engineering, Okayama UniversityIn 2020, the Government of Japan declared "2050 carbon neutral" and launched a long-term strategy to create a "virtuous cycle of economy and environment".(1) Japanese firms possess many technologies that contribute to decarbonization, which is important to expand investment for Green Technology (environmental technology) development. As automobiles are major contributors to greenhouse gas emissions [1], the technological shift towards vehicle powertrain systems is an attempt to lower problems like emissions of carbon dioxide, nitrogen oxides [2]. On the other hand, patent data are the most reliable business performance for applied research and development activities when investigating the knowledge domains or the technology evolution (Wand, 1997). Our paper describes a Japanese patents dataset of the vehicle powertrain systems for hybrid electric vehicle (HEV), battery electric vehicle (BEV) and fuel cell electric vehicles (FCEV). In this paper we create a method of bombinating international patent classification (IPC) and keywords to define "green" patents in vehicle powertrains field, using patent data which were applied to Japan Patent Office recorded on EPO's PATSTAT database during 2010 similar to 2019 year. When analyze patents, it is necessary to consider the social situation of each country including language background, we collect patents description documents (abstracts and titles) not only written in English but also in Japanese. Finally, we build a database includes 6025 green patents' description documents and 266 patents' holding firms. With which we then identify 3756 HEV patents, 1716 BEV patents, and 553 FCEV patents. Data about patent holding firms is also appended. The full dataset may be useful to researchers who would like to do further search like natural language processing and machine learning on patent description documents, statistical data analysis for empirical economics.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2214-5818442022Effects of local land-use policies and anthropogenic activities on water quality in the upstream Sesan River Basin, Vietnam101225ENVo Ngoc QuynhTramGraduate School of Environmental and Life Science, Okayama UniversityHiroakiSomuraGraduate School of Environmental and Life Science, Okayama UniversityToshitsuguMoroizumiGraduate School of Environmental and Life Science, Okayama UniversityMorihiroMaedaGraduate School of Environmental and Life Science, Okayama UniversityStudy region: This study focuses on the upstream Sesan River Basin in the Central Highlands of Vietnam. Study focus: Local land-use policies and human activities can significantly affect hydrology and increase the magnitude of erosion and nutrients in downstream areas. The effects in terrestrial regions on water quality of the target area were evaluated during the 2000-2018 period using the SWAT (Soil and Water Assessment Tool) with updated land-use conditions following the local policy decisions and agricultural practices in different periods. New hydrological insights for the regions: This study indicates that the implementation of the local land-use policies, along with extensive anthropogenic activities, has had significant effects on the downstream aquatic environment as compared with the period before the implementation of the land-use policies. Higher annual sediment, total nitrogen (TN), and total phosphorus (TP) load-ings were found upstream from the Poko Watershed, where range land predominated, and in southern and southwestern Dakbla Watershed, where arable land and permanent cropland pre-dominated. Arable land had the highest proportion of sediment and nutrient loadings into the reach, especially in the 2005-2009 period (conducting afforestation, agricultural expansion, and urbanization) and in the 2010-2014 period (applying crop conversion policy involving a shift from mixed forests to rubber forests). Understanding the watershed characteristics along with the combination of spatial land use, local land-use policies, and agricultural practices will support the implementation of regional land use and water resources management strategies more comprehensively.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409422022Developing a dataset for the expected anthropogenic mercury release in China in response to the Minamata convention on mercury108280ENHabuerGraduate School of Environmental and Life Science, Okayama UniversityTakeshiFujiwaraGraduate School of Environmental and Life Science, Okayama UniversityMasakiTakaokaGraduate School of Engineering, Kyoto UniversityThis paper contains supplementary data in support of a research paper published [1] regarding the expected anthropogenic mercury release in China in response to the Minamata Convention on Mercury (MCM). The dataset provided within this article contains a set of excel spreadsheets. Each spreadsheet contains filtered (collected) and analysed data, i.e., parameters, collected data, calculated and summarized results for mercury distribution by the category of mineral production, intentional uses, secondary metal production, extraction and combustion, and waste treatment in a specific year. The collected (filtered) data in this article consist of the input factor (IF), activity rate data (ARD), output scenario (OS), initial distribution factor (iDF), and redistribution factor (rDF). IF was from the default IF in the United Nations Environment Programme (UNEP) Toolkit Level 2 and published scientific papers. ARD was obtained from the U.S. Geological Survey database, China Statistical Yearbooks, and published scientific papers. The OS content was from the default OS in the UNEP Toolkit Level 2 and published scientific papers. iDF was from the default distribution factor (DF) in the UNEP Toolkit Level 2 and published scientific papers. rDF was from published scientific paper. The mercury input was calculated using IF and ARD. The mercury release to different media in the initial distribution step was calculated using the mercury input and iDF. The release of mercury to the final sinks in the redistribution step was calculated using the amount of sector-specific treatment/disposal, product or by-product, and rDF. The dataset with combination of the collected (filtered) and analyzed data can contribute to an understanding of differences in anthropogenic mercury release before and after implementation of the MCM, especially considering technology transformation in China. Government policymakers involved in hazardous waste management, especially those working on MCM, and engineers and scientists interested in hazardous waste management may benefit from these data. The data can be used for identifying the environmental impact of anthropogenic mercury release before and after the MCM in China. The data can facilitate the creation of strategic management policies for mercury as the MCM is implemented in China.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071372022Dasatinib-induced massive left chylothorax in a patient with chronic myeloid leukemia101662ENGoMakimotoDepartment of Allergy and Respiratory Medicine, Okayama University HospitaMahitoMisawaDepartment of Hematology, Ako Central HospitalYoshinobuMaedaDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiKiuraDepartment of Allergy and Respiratory Medicine, Okayama University HospitaDasatinib, an effective second-generation tyrosine kinase inhibitor, is used to treat breakpoint cluster region-Ableson-positive chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphocytic leukemia. One common adverse event associated with dasatinib use is fluid retention, including pleural effusion. Chylothorax, however, is a rare adverse event. Although the precise mechanism of dasatinib-induced chylothorax is unclear, almost all cases involve right or bilateral chylothorax, and mostly occur within 5 years of dasatinib initiation. Here, we report a rare case of a patient with dasatinib-induced massive left chylothorax 10 years after dasatinib initiation, which improved after dasatinib termination and a switch to bosutinib.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-22754442003Circulating oxidized LDL forms complexes with β(2)-glycoprotein I: implication as an atherogenic autoantigen716726ENKazukoKobayashiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryMakotoKishiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryTatsuyaAtsumiDepartment of Medicine II, Hokkaido University Graduate School of MedicineMaria L.BertolacciniLupus Research Unit, The Rayne Institute, St. Thomas' Hospital LondonHirofumiMakinoDepartment of Medicine and Clinical Science, Okayama University Graduate School of Medicine and DentistryNobuoSakairiDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityItaruYamamotoDepartment of Immunochemistry, Faculty of Pharmaceutical Science, Okayama UniversityTatsujiYasudaDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryMunther A.KhamashtaLupus Research Unit, The Rayne Institute, St. Thomas' Hospital LondonGraham R. V.HughesLupus Research Unit, The Rayne Institute, St. Thomas' Hospital LondonTakaoKoikeDepartment of Medicine II, Hokkaido University Graduate School of MedicineDennis R.VoelkerProgram in Cell Biology, Department of Medicine, National Jewish Medical and Research CenterEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistrybeta(2)-glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (I. Lipid Res., 42: 697, 200 1; J Lipid Res., 43: 1486, 2002) that beta(2)-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the beta(2)-GPI ligands are omega-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with beta(2)-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the omega-carboxyl function of the beta(2)-GPI ligands was necessary for beta(2)-GPI binding. The ligand-mediated noncovalent interaction of beta(2)-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable beta(2)-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence Of beta(2)-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing beta(2)-GPI or LDL.jlr Thus, the beta(2)-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0022-22754392002ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages14861495ENQingpingLiuDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryKazukoKobayashiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryJun-ichiFurukawaDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryNobuoSakairiDivision of Bioscience, Graduate School of Environment Earth Science, Hokkaido UniversityAkimasaIwadoGraduate School of Natural Science and Technology, Okayama UniversityTatsujiYasudaDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and DentistryTakaoKoikeDepartment of Medicine II, Hokkaido University Graduate School of MedicineDennis R.VoelkerProgram in Cell Biology, Department of Medicine, National Jewish Medical and Research CenterEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistrybeta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K, E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Welker, and T. Koike. 2001. A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J Lipid Res. 42: 697-709). In the present study, we demonstrate that omega-carboxylated 7-ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytxidecanoate (13-COOH-7KC), also showed a significant interaction with beta(2)-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612902022Acute acalculous cholecystitis caused by SARS-CoV-2 infection: A case report and literature review106731ENHanaFutagamiCenter for Graduate Medical Education, Okayama University HospitalHirokiSatoDepartment of Gastroenterological Surgery, Okayama University HospitalRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University HospitalKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University HospitalTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University HospitalToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University HospitalBackground: Emerging data indicate that gastrointestinal disorders, in addition to pulmonary dysfunction, are also hallmarks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case presentation: A 42-year-old man with maintenance hemodialysis developed high fever and dyspnea. He was positive for SARS-CoV-2 and was diagnosed with pneumonia. After treatment for SARS-CoV-2, his respiratory condition improved. However, he developed right upper quadrant pain with elevated inflammatory markers (white blood cells, 21,160/mu L; c-reactive protein, 163.9 mg/L) on the 13th day. Abdominal computed tomography revealed acute acalculous cholecystitis. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed together with antibiotic therapy, which resulted in improvement of symptoms. Laparoscopic cholecystectomy was performed 36 days after PTGBD. <br>
Conclusion: We report a rare case of acute acalculous cholecystitis (AAC) following pneumonia caused by SARS-CoV-2 infection. We also conducted a literature search to characterize SARS-CoV-2-related cholecystitis. Infection with SARS-CoV-2 is an important trigger for AAC, and appropriate therapeutic alternatives should be cautiously selected according to individual cases.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2090-1232352022Spred2 controls the severity of Concanavalin A-induced liver damage by limiting interferon-gamma production by CD4(+) and CD8(+) T cells7186ENCuimingSunDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayoshiFujisawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiakiOharaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityQiuyingLiuDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenCaoDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityXuYangDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeizoYoshimuraDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySteven L.KunkelDepartment of Pathology, University of Michigan Medical SchoolAkihiroMatsukawaDepartment of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Mitogen-activated protein kinases (MAPKs) are involved in T cell-mediated liver damage. However, the inhibitory mechanism(s) that controls T cell-mediated liver damage remains unknown. Objectives: We investigated whether Spred2 (Sprouty-related, EVH1 domain-containing protein 2) that negatively regulates ERK-MAPK pathway has a biological impact on T cell-mediated liver damage by using a murine model. Methods: We induced hepatotoxicity in genetically engineered mice by intravenously injecting Concanavalin A (Con A) and analyzed the mechanisms using serum chemistry, histology, ELISA, qRT-PCR, Western blotting and flow cytometry. Results: Spred2-deficient mice (Spred2(-/-)) developed more sever liver damage than wild-type (WT) mice with increased interferon-gamma (IFNy) production. Hepatic ERK phosphorylation was enhanced in Spred2(-/-) mice, and pretreatment of Spred2(-/-) mice with the MAPK/ERK inhibitor U0126 markedly inhibited the liver damage and reduced IFN gamma production. Neutralization of IFNy abolished the damage with decreased hepatic Stat1 activation in Spred2(-/-) mice. IFN gamma was mainly produced from CD4(+) and CD8(+) T cells, and their depletion decreased liver damage and IFN gamma production. Transplantation of CD4(+) and/or CD8(+) T cells from Spred2(-/-) mice into RAG1(-/-) mice deficient in both T and B cells caused more severe liver damage than those from WT mice. Hepatic expression of T cell attractants, CXCL9 and CXCL10, was augmented in Spred2(-/-) mice as compared to WT mice. Conversely, liver damage, IFN gamma production and the recruitment of CD4(+) and CD8(+) T cells in livers after Con A challenge were lower in Spred2 transgenic mice, and Spred2-overexpressing CD4(+) and CD8(+) T cells produced lower levels of IFN gamma than WT cells upon stimulation with Con A in vitro. Conclusion: We demonstrated, for the first time, that Spred2 functions as an endogenous regulator of T cell IFNy production and Spred2-mediated inhibition of ERK-MAPK pathway may be an effective remedy for T cell-dependent liver damage.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2059-7029642021Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study100191ENK.HottaCenter for Innovative Clinical Medicine, Okayama University HospitalS.SaekiDepartment of Respiratory Medicine, Kumamoto University HospitalM.YamaguchiDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer CenterD.HaradaDepartment of Thoracic Oncology, National Hospital Organization Shikoku Cancer CenterA.BesshoDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalK.TanakaDepartment of Respiratory Medicine, Kyushu University HospitalK.InoueDepartment of Respiratory Medicine, Kitakyushu Municipal Medical CenterK.GembaDepartment of Respiratory Medicine, Chugoku Central HospitalM.ShiojiriDepartment of Respiratory Medicine, Japanese Red Cross Okayama HospitalY.KatoCenter for Innovative Clinical Medicine, Okayama University HospitalT.NinomiyaDepartment of Respiratory Medicine, Okayama University HospitalT.KuboDepartment of Respiratory Medicine, Okayama University HospitalJ.KishimotoCenter for Clinical and Translational Research, Kyushu University HospitalY.ShioyamaClinical Radiology, Radiology Informatics and Network, Graduate School of Medical Sciences, Kyushu UniversityK.KatsuiDepartment of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJ.SasakiResearch and Development Center for New Medical Frontiers, Kitasato University School of MedicineK.KiuraDepartment of Respiratory Medicine, Okayama University HospitalK.SugioDepartment of Thoracic and Breast Surgery, Oita UniversityBackground: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. <br>
Patients and methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m(2) each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. <br>
Results: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade >= 3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade >= 3 or treatment-related death did not occur. <br>
Conclusions: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582021Semi-quantitative arthroscopic scoring system is related to clinical outcomes in patients after medial meniscus posterior root repairENXimingZhangDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKeisukeKintakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHaoweiXueDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesShinichiMiyazawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesBackground<br>
Different methods are available to assess the healing status of repaired root for medial meniscus posterior root tears (MMPRT) using second-look arthroscopy. However, few studies are comparing them or validating their usefulness. Therefore, it was hypothesized that the semi-quantitative arthroscopic score might correlate more with 1-year clinical outcomes in patients with MMPRT than the qualitative evaluation. <br>
Methods<br>
Data of 61 patients who underwent MMPRT pullout repair and second-look arthroscopy were retrospectively evaluated. The semi-quantitative arthroscopic scoring system was divided into three evaluation criteria: scores from 0 to 10 points include the width of the bridging tissue, stability of the repaired root, and synovial coverage. The qualitative evaluation was classified into 4 status; complete healing, lax healing, scar tissue healing, and failed healing according to the stability and mobility of the repaired root. Multivariate linear regression analyses were used to identify predictors of 1-year postoperative clinical outcomes, including Knee Injury and Osteoarthritis Outcome, Lysholm, or International Knee Documentation Committee scores. Spearman's correlation analysis was used to analyze the correlation between second-look arthroscopic score/qualitative evaluation and 1-year postoperative clinical outcomes. In addition, the optimal cutoff point of semi-quantitative arthroscopic score was determined by receiver operating characteristic (ROC) curve. The Mann–Whitney U test was used to compare clinical outcomes between patients with semi-quantitative arthroscopic scores ≥8 and scores <8. <br>
Results<br>
All clinical scores significantly improved at 1 year postoperatively. A good correlation was observed between the semi-quantitative score and clinical scores, but none between qualitative evaluation and clinical scores. The optimal cutoff point of semi-quantitative second-look arthroscopic score was 8 points. Significantly, better clinical outcomes were observed in patients with semi-quantitative scores ≥8 points. <br>
Conclusions<br>
All 1-year postoperative clinical scores were significantly improved. The semi-quantitative arthroscopic scores correlate more with 1-year clinical outcomes in patients with MMPRT than the qualitative evaluation. Level of evidence IV case series study.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1042-4431742021The Conditional Volatility Premium on Currency Portfolios101415ENJoseph P.ByrneEdinburgh Business School (Economics), School of Social Sciences, Heriot-Watt UniversityRyutaSakemotoGraduate School of Humanities and Social Sciences, Okayama UniversityOur paper examines conditional risk-return relations in a number of currency investment strategies, while modeling economic states using a large number of underlying risk factors. We identify a time-varying relationship between currency returns and volatility risk for most currency portfolios. In particular, value and momentum portfolios present risk-return relationships which switch sign, depending upon economic states. The positive relationship for the value portfolio is associated with “flight to quality” periods and the mean reversion for nominal exchange rates during financial crises. The positive relationship for the momentum portfolio is linked to the US and global business cycles and investors require positive compensation for risk in recessions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0167577X3072021Clarification of degradation mechanism on retinal prosthesis using photoelectric dyes coupled to polyethylene film by mass spectrometry130978ENKoichiroYamashitaGraduate School of Natural Science and Technology, Okayama UniversityMayuMitsuiGraduate School of Natural Science and Technology, Okayama UniversityToshihikoMatsuoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTetsuyaUchidaGraduate School of Natural Science and Technology, Okayama UniversityPhotoelectric dyes have stimulated retinal neurons by absorbing light and generating an electric potential. Therefore, a photoelectric dye was used to develop a retinal prosthesis to restore vision loss due to retinitis pigmentosa. The retinal prosthesis, referred to as a dye-coupled film, was prepared by chemically coupling the dyes to a polyethylene film surface through amide bonds. However, the coupled dyes decreased during an implantation test in a monkey eye. This study clarifies the degradation mechanism of the dye-coupled film. Since the dyes were selectively coupled to the film surface, it is difficult to detect the eliminated dyes in a solution. Therefore, a model compound that mimicked the chemical structure of the dye-coupled film by converting the carboxylic acid of dye to the amide bond is used. It was found that the elimination of the side chain, including the amide bond, occurred before the degradation of the conjugated structure according to mass spectrometry of the model compound. The degradation mechanism of the dye-coupled film was predicted based on that of the model compound. It was concluded that chemical bonds between the dye and the film surface were preferentially decomposed, leading to the detachment of the dyes from the film surface.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2214-5818362021Environmental flow sustainability in the Lower Limpopo River Basin, Mozambique100843ENOsvaldo SilvaZefanias NhassengoEscola Superior de Neg´ocios e Empreendedorismo de Chibuto, Universidade Eduardo MondlaneHiroakiSomuraGraduate School of Environmental and Life Science, Okayama UniversityJune IIIWolfeTexas A&M AgriLife, Blackland Research & Extension CenterStudy region: This study focuses on the Lower Limpopo River basin (LLRB) in Mozambique, Africa. Study focus: Maintaining environmental flows necessary for ecosystem sustainability represents a significant challenge to water resource management. In this study the sustainability of LLRB was evaluated by comparing hydrologic availability with ecological and anthropogenic needs. Current river ecological status was scored with a habitat integrity index verified through ground-truthing field surveys and aerial imagery data. Local stakeholder interviews were used to further evaluate the habitat index scores. Deficiencies between water availability and ecological-human requirements were assessed with a water scarcity index.<br>
New Hydrological Insights for the Region: Four environmental flow categories defined as "Excellent", "Fair", "Poor", and "Degraded" coincided to approximately 50 %, 39 %, 27 %, and 14 % of the natural mean annual flow, respectively. Stakeholder interview responses indicated annual water shortages currently occur between August and November and coincide with "Poor" and "Degraded" environmental flow conditions. Water supplies appear to meet consumption needs when calculated on an annual basis with the water scarcity index. However, when calculated monthly, there is not enough to meet human water demand between August and October. This deficit period will likely expand from June to November due to projected increases in future water demands. As the greatest water use in the basin is agricultural irrigation, long-term environmental flows sustainability will likely depend upon effective irrigation management.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama000925415592021Experimental variable effects on laser heating of inclusions during Raman spectroscopic analysis119928ENYuukiHagiwaraGraduate School of Science, Hokkaido UniversityKentaYoshidaResearch Institute for Marine Geodynamics, Japan Agency for Marine-Earth Science and Technology (JAMSTEC)AkiraYonedaInstitute for Planetary Materials, Okayama UniversityJunjiTorimotoOre Genesis Research Unit, Project Team for Development of New-Generation Research Protocol for Submarine Resources, Japan Agency for Marine-Earth Science and Technology (JAMSTEC)JunjiYamamotoThe Hokkaido University Museum Raman spectroscopy for fluid, melt, and mineral inclusions provides direct insight into the physicochemical conditions of the environment surrounding the host mineral at the time of trapping. However, the obtained Raman spectral characteristics such as peak position are modified because of local temperature enhancement of the inclusions by the excitation laser, which might engender systematic errors and incorrect conclusions if the effect is not corrected. Despite the potentially non-negligible effects of laser heating, the laser heating coefficient (B) (°C/mW) of inclusions has remained unsolved. For this study, we found B from experiments and heat transport simulation to evaluate how various parameters such as experimental conditions, mineral properties, and inclusion geometry affect B of inclusions. To assess the parameters influencing laser heating, we measured B of a total of 19 CO2-rich fluid inclusions hosted in olivine, orthopyroxene, clinopyroxene, spinel, and quartz. Our results revealed that the measured B of fluid inclusions in spinel is highest (approx. 6 °C/mW) and that of quartz is lowest (approx. 1 × 10−2 °C/mW), consistent with earlier inferences. Our simulation results show that the absorption coefficient of the host mineral is correlated linearly with B. It is the most influential parameter when the absorption coefficient of the host mineral (αh) is larger than that of an inclusion (αinc). Furthermore, although our results indicate that both the inclusion size and depth have little effect on B if αh > αinc, the thickness and radius of the host mineral slightly influence B. These results suggest that the choice of inclusion size and depth to be analyzed in a given sample do not cause any systematic error in the Raman data because of laser heating, but the host radius and thickness, which can be adjusted to some degree at the time of sample preparation, can cause systematic errors between samples.Our results demonstrate that, even with laser power of 10 mW, which is typical for inclusion analysis, the inclusion temperature rises to tens or hundreds of degrees during the analysis, depending especially on the host mineral geometry and optical properties. Therefore, correction of the heating effects will be necessary to obtain reliable data from Raman spectroscopic analysis of inclusions. This paper presents some correction methods for non-negligible effects of laser heating.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama199179022021Prevention and early management of carotid blowout syndrome for patients receiving head and neck salvage boron neutron capture therapy (BNCT)ENTien-LiLanDivision of Radiotherapy, Department of Oncology, Taipei Veterans General HospitalFeng-ChiChangDepartment of Radiology, Taipei Veterans General HospitalChun-WeiWangDivision of Radiotherapy, Department of Oncology, Taiwan University HospitalKazuyoIgawaNeutron Therapy Research Center, Okayama UniversitySzu-HsienWuDivision of Plastic and Reconstructive Surgery, Taipei Veterans General HospitalWen-LiangLoDivision of Oral and Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General HospitalYi-WeiChenDivision of Radiotherapy, Department of Oncology, Taipei Veterans General HospitalBackground/purpose<br/>
The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS. <br/>
Materials and methods<br/>
We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy. <br/>
Results<br/>
The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up. <br/>
Conclusion<br/>
Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama246812452021Profile of down syndrome–associated malignancies: Epidemiology, clinical features and therapeutic aspectsENAkiraShimadaDepartment of Pediatric Hematology, Okayama University HospitalDown syndrome (DS) is a congenital chromosomal abnormality caused by the presence of all or part of a third copy of chromosome 21 (+21). DS is frequently complicated by congenital heart or digestive tract diseases at birth. DS patients are prone to infections and have mental retardation, with dementia such as Alzheimer's disease showing in later life. Furthermore, malignancies with specific characteristics are also highly reported in DS patients compared with non-DS patients. Therefore, DS is believed to be a cancer predisposition syndrome due to the chromosomal instability. Acute myeloid leukemia (AML) and especially acute megakaryoblastic leukemia (AMKL) by French-American-British (FAB) classification are the most frequent hematological malignancies in DS patients, occurring at a rate that is 500 times higher than that in non-DS patients. Interestingly, transient abnormal myelopoiesis (TAM) is observed in approximately 10% of DS neonates with GATA1 mutations, and most TAM patients are asymptomatic and show spontaneous regression; however, about 10%–20% of TAM cases are fatal because of complications such as fetal effusion, liver fibrosis, and other complications.Acute lymphoblastic leukemia (ALL) is also associated with DS, occurring at a rate that is 20 times higher than that in non-DS patients. Furthermore, the prognosis of DS-ALL patients is poorer than that of non-DS-ALL patients. A recent genetic analysis revealed that more than half of DS-ALL cases have a mutation in the CRLF2–JAK pathway, indicating that JAK inhibitors might have a limited effect for DS-ALL patients.Notably, solid tumors such as neuroblastoma, Wilms tumor, and brain tumor, which are frequently observed in non-DS children, are rarely reported in DS children. The reason remains unknown, but it may be because of the triplication of the Down syndrome critical region 1 (DSCR1) gene on chromosome 21. In adult patients with DS, the expected age-adjusted incidence rates of solid tumors are low compared with age-matched euploid cohorts for most cancers except for testicular cancer. Although the average life expectancy of patients with DS will increase with advances in healthcare, the detailed health problems including cancer rates in older DS patients remain unknown. Therefore, these issues will be needed to be addressed in future studies.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama199179021612021A comparison of colorimetric and visual methods for the assessment of masticatory performance with color-changeable chewing gum in older persons380388ENYoshihiroKugimiyaDepartment of Removable Prosthodontics and Gerodontology, Tokyo Dental CollegeYutakaWatanabeGerodontology, Department of Oral Health Science, Faculty of Dental Medicine, Hokkaido UniversityMakiShirobeThe Tokyo Metropolitan Support Center for Preventative Long-term and Frail Elderly CareYoshikoMotohashiResearch Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of GerontologyKeikoMotokawaResearch Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of GerontologyAyakoEdahiroResearch Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of GerontologyYukiOharaResearch Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of GerontologyMasahiroRyuDepartment of Removable Prosthodontics and Gerodontology, Tokyo Dental CollegeKentaroIgarashiRemovable Prosthodontics, Nihon University School of Dentistry at MatsudoDaichiHoshinoSpecial Needs Dentistry, Division of Community Based Comprehensive Dentistry, School of Dentistry, Showa UniversityJunkoNakajimaDepartment of Oral Medicine and Hospital Dentistry, Tokyo Dental CollegeTakayukiUedaDepartment of Removable Prosthodontics and Gerodontology, Tokyo Dental CollegeYuTaniguchiCenter for Health and Environmental Risk Research, National Institute for Environmental StudiesToruOgawaDivision of Advanced Prosthetic Dentistry, Tohoku University Graduate School of DentistryKenjiMaekawaDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsushiTamakiDepartment of Critical Care Medicine and Dentistry, Division of Prosthodontic Dentistry for Function of TMJ and Occlusion, Graduate School of Dentistry, Kanagawa Dental UniversityTakuoKubokiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAkihikoKitamuraResearch Team for Social Participation and Health Promotion, Tokyo Metropolitan Institute of GerontologyShojiShinkaiSocial Sciences and Human Care, Tokyo Metropolitan Institute of GerontologyHirohikoHiranoResearch Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of GerontologyBackground/purpose<br/>
Color-changeable chewing gum is used for the evaluation of masticatory performance. However, it is currently unclear whether colorimetric and visual assessment methods yield consistent results. This study aimed to clarify the consistency between colorimetric and visual methods used for the evaluation of color changes in color-changeable chewing gum. <br/>Materials and methods<br/>
The sample comprised 644 older persons (mean age, 75.4 ± 6.4 years). The chewing gum was masticated 60 times at the participant's own chewing rate and then expectorated. The color of the chewing gum was evaluated with the ΔE values and a∗ values, measured using a colorimeter, and the 10 Color Shades (10CSh) and 5 Color Scales (5CSc), using visual evaluation. Spearman's correlation analysis was performed to examine the correlation between the results obtained by the four methods. The significance level was set at α = 0.05. <br/>Results<br/>
The ΔE values, a∗ values, 10CSh scores, and 5CSc scores were all significantly correlated. The highest correlation coefficient (0.979) was between the ΔE values and a∗ values. The lowest correlation coefficient (0.847) was between the a∗ values and 5CSc scores. Decreased masticatory performance was observed with increased age. <br/>
Conclusion<br/>
Significant correlations were found for all four methods used in the assessment of masticatory performance with color-changeable chewing gum. While visually based assessments are valid, colorimetric methods are more sensitive to smaller changes in masticatory performance.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama26663643212021Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations100107ENKiichiroNinomiyaDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShunsukeTeraokaInternal Medicine III, Wakayama Medical UniversityYoshitakaZenkeDepartment of Thoracic Oncology, National Cancer Center Hospital EastHirotsuguKenmotsuDivision of Thoracic Oncology, Shizuoka Cancer CenterYukikoNakamuraDepartment of Respiratory Medicine, Yokohama Municipal Citizen’s HospitalYusukeOkumaDepartment of Thoracic Oncology, National Cancer Center HospitalAkihiroTamiyaDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterKanameNosakiDepartment of Thoracic Oncology, National Cancer Center Hospital EastMasahiroMoriseDepartment of Respiratory Medicine, Nagoya University Graduate School of MedicineKeijuAokageDepartment of Thoracic Surgery, National Cancer Center Hospital EastYukoOyaDepartment of Thoracic Oncology, Aichi Cancer Center HospitalToshiyukiKozukiDepartment of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer CenterTomohiroSakamotoDivision of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori UniversityKentaroTanakaResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityHisashiTanakaDepartment of Respiratory Medicine, Hirosaki University Graduate School of MedicineJunkoTanizakiDepartment of Medical Oncology, Kishiwada City HospitalSatoruMiuraDepartment of Internal Medicine, Niigata Cancer Center HospitalHideakiMizutaniDepartment of Thoracic Oncology, Saitama Cancer CenterEisakuMiyauchiDepartment of Respiratory Medicine, Tohoku University HospitalOuYamaguchiDepartment of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical CenterNoriyukiEbiDepartment of Respiratory Oncology, Iizuka HospitalYasushiGotoDepartment of Thoracic Oncology, National Cancer Center HospitalTakaakiSasakiRespiratory Center, Asahikawa Medical UniversityHarukoDagaDepartment of Medical Oncology, Osaka City General HospitalSatoshiMoritaDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine Kyoto UniversityTakeharuYamanakaDepartment of Biostatistics, Yokohama City University School of MedicineShinsukeAmanoJapan Federation of Cancer Patient GroupsKazuoHasegawaJapan Lung Cancer AllianceChiyo K.ImamuraAdvanced Cancer Translational Research Institute, Showa UniversityKenichiSuzukiDivision of Applied Pharmaceutical Education and Research, Hoshi UniversityKazukoNakajimaDepartment of Nursing and The Division of Stem Cell Transplantation, Shizuoka Cancer CenterHitomiNishimotoDepartment of Nursing, Okayama University HospitalSatoshiOizumiDepartment of Respiratory Medicine, National Hospital Organization Hokkaido Cancer CenterToyoakiHidaDepartment of Thoracic Oncology, Aichi Cancer Center HospitalKatsuyukiHottaCenter for Clinical Oncology, Okayama University HospitalYuichiTakiguchiDepartment of Medical Oncology, Chiba University HospitalPatients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama122686152412021Swarming and mating behavior in Ephemera orientalis Mclachlan, 1875 (Ephemeroptera: Ephemeridae) with morphological analyses376382ENTakahisaMiyatakeGraduate School of Environmental and Life Science, Okayama UniversityTaichiSugeGraduate School of Environmental and Life Science, Okayama UniversityShunsukeSuzakiGraduate School of Environmental and Life Science, Okayama UniversityShintaroTanabeGraduate School of Environmental and Life Science, Okayama UniversityRyoIshiharaGraduate School of Environmental and Life Science, Okayama UniversityKentarouMatsumuraGraduate School of Environmental and Life Science, Okayama UniversitySwarming and mating behaviors of a mayfly species, Ephemera orientalis Mclachlan, 1875 were observed in 2015, 2016, and 2018 at a river bank of the Asahi River, Japan. Males started to make swarms between late April and middle May in 2016 and 2018. The numbers of mated pairs in a swarm correlated with the numbers of flying males in a swarm in 2016 and 2018. Swarms were formed during a limited period at dusk most probably because that interval is free from natural enemies. Males competed with each other to copulate with females in swarms. We clarified the function of the forelegs of males, which are significantly longer than those of females. Males used their forelegs to hold up a female from below. Besides forelegs, males have longer tails than females. We will discuss why sexual differences are found in these traits. Our results represent the first observation of swarm mating behavior in E. orientalis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0914-50877812021Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats1723ENRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruKobayashiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoKawasaki University of Medical WelfareNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiIto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Right ventricular (RV) function is important for outcomes in pulmonary hypertension. Evaluation of RV myocardial characteristics is useful to assess the disease severity. Shear wave elastography (SWE) provides information of shear wave (SW) elasticity, which is related to tissue hardness, and SW dispersion slope, which reflects tissue viscosity. This study aimed to test the hypothesis that SW elasticity is increased and SW dispersion slope is decreased in the right ventricle of monocrotaline (MCT)-induced pulmonary hypertension rats. <br>
<br>
Methods: Rats were divided into MCT-induced pulmonary hypertension group (n = 10) and control group (n = 10). SW elasticity and SW dispersion slope were measured on excised hearts. Myocardial fibrosis was evaluated histologically. <br>
<br>
Results: RV hypertrophy was observed in the MCT group. SW elasticity of right ventricle was higher in the MCT group than in the control group (3.5 ± 0.9 kPa vs. 2.5 ± 0.4 kPa, p < 0.01). SW dispersion slope of right ventricle was lower in the MCT group than in the control group (5.3 ± 1.7 m/s/kHz vs. 7.7 ± 1.5 m/s/kHz, p < 0.01). The fibrosis area of right ventricle was increased in MCT group compared with control group (18 ± 5% vs. 8 ± 3%, p < 0.01), and was positively related to SW elasticity and negatively related to SW dispersion slope. <br>
<br>
Conclusions: Higher SW elasticity and lower SW dispersion slope were observed in the fibrotic myocardium of right ventricle in MCT-induced pulmonary hypertension rats. SWE may have the potential to evaluate RV function by assessing myocardial characteristics. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama22121374262021The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone100330ENTatsuoOkuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasahiroHiasaDepartment of Biomaterials and Bioengineerings, University of Tokushima Graduate School of DentistryShojiRyumonKishoOnoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceYukiKunisadaDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceAkiraSasakiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceG. DavidRoodmanDepartment of Medicine, Hematology Oncology, Indiana University School of MedicineFletcher A.WhiteDepartment of Anesthesia, Paul and Carole Stark Neurosciences Research InstituteToshiyukiYonedaDepartment of Cellular and Molecular Biochemistry, Osaka University Graduate School of DentistryBone pain is a common complication of breast cancer (BC) bone metastasis and is a major cause of increased morbidity and mortality. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed. Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Consistent with these in vivo results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama17439191862021Learning curves of minimally invasive donor nephrectomy in a high-volume center: A cohort study of 1895 consecutive living donors712ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHendrikus J.A.N.KimenaiDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamTurkanTerkivatanDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamKhe T.C.TranDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamJan N.M.IjzermansDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamRobert C.MinneeDepartment of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Centre RotterdamBackground<br/>
Few studies have investigated the learning curves of minimally invasive donor nephrectomy (MIDN) using the cumulative sum (CUSUM) analysis. In addition, no study has compared the learning curves of the different surgical MIDN techniques in one cohort study using the CUSUM analysis. This study aims to evaluate and compare learning curves for several MIDN using the CUSUM analysis. <br/>
Methods<br/>
A retrospective review of consecutive donors, who underwent MIDN between 1997 and 2019, was conducted. Three laparoscopic-assisted techniques were applied in our institution and included for analysis: laparoscopic (LDN), hand-assisted retroperitoneoscopic (HARP), and robot-assisted laparoscopic (RADN) donor nephrectomy. The outcomes were compared based on surgeon volume to develop learning curves for the operative time per surgeon. <br/>
Results<br/>
Out of 1895 MIDN, 1365 (72.0%) were LDN, 427 (22.5%) were HARP, and 103 (5.4%) were RADN. The median operative time and median blood loss were 179 (IQR, 139–230) minutes and 100 (IQR, 40–200) mL, respectively. The incidence of major complication was 1.2% with no mortality, and the median hospital stay was three (IQR, 3–4) days. The CUSUM analysis resulted in learning curves, defined by decreased operative time, of 23 cases in LDN, 45 cases in HARP, and 26 cases in RADN. <br/>
Conclusions<br/>
Our study shows different learning curves in three MIDN techniques with equal post-operative complications. The LDN and RADN learning curves are shorter than that of the hand-assisted donor nephrectomy. Our observations can be helpful for informing the development of teaching requirements for fellows to be trained in MIDN.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003192013112021Thermocapillary effects in two-phase medium and applications to metal-silicate separation106640ENYanickRicardUniversité de Lyon, ENSL, UCBL, Laboratoire LGLTPEStéphaneLabrosseUniversité de Lyon, ENSL, UCBL, Laboratoire LGLTPEHidenoriTerasakiOkayama University, Department of Earth SciencesDavidBercoviciYale University, Department of Earth & Planetary Sciences The separation of a liquid phase from a solid but deformable matrix made of mineral grains is controlled at small scale by surface tension. The role of interfacial surface tension is twofold as it explains how a small volume of liquid phase can infiltrate the grain boundaries, be distributed and absorbed in the matrix, but after complete wetting of the grains, surface tension favors the self-separation of the liquid and solid phases. Another consequence of surface tension is the existence of Marangoni forces, which are related to the gradients of surface tension that are are usually due to temperature variations. In this paper, using a continuous multi-phase formalism we clarify the role of these different effects and quantify their importances at the scale of laboratory experiments and in planets. We show that Marangoni forces can control the liquid metal-solid silicate phase separation in laboratory experiments. The Marangoni force might help to maintain the presence of metal at the surface of asteroids and planetesimals that have undergone significant melting.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama187854092021A case of a middle-aged patient with a ventricular septal defect complicated by severe pulmonary hypertension-stepwise surgical repair with pulmonary vasodilators-ENAnnaKanaiDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineNorimichiKoitabashiDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHidemiSorimachiDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineYoheiIshibashiDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineTakashiNagasakaDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineNoriakiTakamaDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineKatsuraSomaDepartment of Cardiovascular Medicine, The University of Tokyo HospitalAtsushiYaoDepartment of Cardiovascular Medicine, The University of Tokyo HospitalShingoKasaharaDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahikoKurabayashiDepartment of Cardiovascular Medicine, Gunma University Graduate School of MedicineWe report a case of ventricular septal defect (VSD) in which we attempted to treat pulmonary arterial hypertension (PAH) with the goal of VSD closure in an adult with suspected Eisenmenger syndrome in childhood. Four years previously (age 41 years), she was referred to our department due to repeated hemoptysis requiring further treatment of PAH. We started combination therapy with several pulmonary vasodilators. Two years later, her pulmonary vascular resistance (PVR) was improved but still not at the level where VSD closure was possible. To control the increased PA flow resulting from intensive PAH treatment and to reduce the risk of hemoptysis, we performed pulmonary artery banding (PAB). As the risk of hemoptysis decreased, a prostacyclin analog was introduced, and the dose was increased. More than 1 year after PAB, active vasoactivity testing became positive, suggesting that the pulmonary vascular lesion was now “reversible”. We performed VSD closure and atrial septal defect creation even though her PVR was still high. After the operation, her exercise capacity was remarkably improved. We suggest that stepwise surgical repair with pulmonary vasodilators is an important treatment option for select patients with VSD with severe PAH.Learning objectiveAdvances in pulmonary arterial hypertension (PAH) treatment have led to the use of a “treat-and-repair” strategy to close the intracardiac shunt after PAH treatment in select patients with adult congenital heart disease. In our case, ventricular septal defect (VSD) closure was achieved with stepwise surgical repair and a combination of pulmonary vasodilators, even though long-standing severe PAH with persistent hemoptysis remained. Even after a long period of exposure to high blood flow, this strategy may reduce pulmonary vascular resistance and permit eventual closure of the VSD.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama240545692021Intravesical Therapy in Patients with Intermediate-risk Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease RecurrenceENEkaterinaLaukhtinaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaMohammadAbufarajDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaAbdallahAl-AniDivision of Urology, Department of Special Surgery, Jordan University Hospital, The University of JordanMustafa RamiAliDivision of Urology, Department of Special Surgery, Jordan University Hospital, The University of JordanKeiichiroMoriDepartment of Urology, The Jikei University School of MedicineMarcoMoschiniDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFahadQuhalDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaRezaSari MotlaghDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaBenjaminPradereDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaVictor M.SchuettfortDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaHadiMostafaeiDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNico C.GrossmannDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaHarunFajkovicDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFrancescoSoriaDivision of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of TorinoDmitryEnikeevInstitute for Urology and Reproductive Health, Sechenov UniversityShahrokh F.ShariatDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaContext<br/>
Patients with intermediate-risk non–muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. <br/>Objective<br/>
To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. <br/>
Evidence acquisition<br/>
The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. <br/>Evidence synthesis<br/>
Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26–1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39–2.11 vs OR 0.93, 95% CI 0.40–2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). <br/>
Conclusions<br/>
Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. <br/>Patient summary<br/>
A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama187853521432021New metal complexes derived from diacetylmonoxime-n(4)antipyrinylthiosemicarbazone: Synthesis, characterization and evaluation of antitumor activity against Ehrlich solid tumors induced in mice102993ENBishoyEl-AaragDivision of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityFathyEl-SaiedDepartment of Chemistry, Faculty of Science, Menoufia UniversityTarekSalemDepartment of Biochemistry, College of Medicine, Qassim UniversityNesrinKhedrDepartment of Chemistry, Faculty of Science, Menoufia UniversityShaden A.M.KhalifaDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityHesham R.El-SeediDepartment of Chemistry, Faculty of Science, Menoufia University The present study aimed to synthesize new metal complexes of diacetylmonoxime-N(4)antipyrinylthiosemicarbazone ligand and evaluate their antitumor activity. New complexes with ferric, cobalt, nickel and copper ions were prepared. Elemental, 1H Nuclear magnetic resonance, Mass spectroscopy, Electron paramagnetic resonance, Fourier Transform InfraredSpectroscopy, Ultraviolet–visible and thermal gravimetricanalysis were used to characterize the obtained complexes 1–11. An in vivo tumor model was established to investigate the effect of the naked ligand and its metal complexes 2, 5 and 8. Ehrlich ascites carcinoma solid tumor was induced in mice through subcutaneous inoculation of Ehrlich ascites carcinoma cells. The volumes of the formed solid tumors, the alanine transaminase, aspartate transaminase, albumin concentration in the serum, as well as the levels of Ki67 and p53 proteins in tumor and liver tissues were detected. All the tested complexes, especially complex 5, possessed proliferative inhibition manifested as the reduction of the tumor volume, Alanine aminotransferase & Aspartate aminotransferase activity, and the level of the Ki67 protein. Additionally, they restored the albumin concentration to normal levels as well increased the level of pro-apoptotic p53 protein. In conclusion, the antitumor activity of the newly synthesized metal complexes against Ehrlich ascites carcinoma solid tumors was proved to be mediated by the inhibition of Ki67 and induction of p53 proteins.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama193004331632021Dysostosis in mucopolysaccharidosis type 2: A case of longitudinal follow up and literature review656660ENTomoakiSasakiDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMikiOgataDepartment of Radiology, Asahikawa Medical UniversityAyaKajihamaDepartment of Pediatrics, Asahikawa Medical UniversityKouichiNakauDepartment of Pediatrics, Asahikawa Medical UniversityAtsutakaOkizakiDepartment of Radiology, Asahikawa Medical University Mucopolysaccharidosis type 2 is a congenital lysosomal disease characterized by iduronate-2-sulfatase deficiency, which leads to excessive accumulation of glycosaminoglycans in tissue. Dysostosis, which primarily involves decreased bone mineralization with morphological changes in the bone, is a major skeletal condition in mucopolysaccharidosis, but its pathophysiology is not well known. Here, we report a case of mucopolysaccharidosis type 2 diagnosed at the age of 2 years with longitudinal follow-up data for more than 15 years. Although the patient underwent bone marrow transplantation, the developmental quotient did not improve, and cranial hyperostosis progressed prominently with a faintly dilated perivascular space. Other dysostoses and contraction of the joints were observed but did not improve either.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666548452021The usefulness and safety of the simultaneous parallel anterior and posterior combined lumbar spine surgery using intraoperative 3D fluoroscopy-based navigation (SPAPS)100047ENHisanoriIkumaDepartment of Orthopaedic Surgery, Kagawa Prefectural Central Hospital,TomohikoHiroseDepartment of Orthopaedic Surgery, Kagawa Prefectural Central Hospital,ShinichiroTakaoDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceKazutoshiOtsukaOtsuka Orthopaedic Surgery ClinicKeisukeKawasakiDepartment of Orthopaedic Surgery, Kagawa Prefectural Central Hospital,Background<br/>
The combined anterior-posterior surgery in the lateral decubitus position generally needs the intraoperative repositioning. However, prolonged surgical time and increased medical costs due to intraoperative repositioning have been problematic. In recent years, there have been reports of combined anterior-posterior procedure with a single position performing anterior and posterior fixation consecutively where the patient remains in the lateral decubitus position (single surgeon method-SS method). We had further advanced this method, and have adopted the Simultaneous Parallel Anterior and Posterior combined lumbar spine Surgery using intraoperative 3D fluoroscopy-based navigation (SPAPS method), where anterior and posterior procedure are performed independently by two spine surgeons.<br/>
Methods<br/>
66 cases that underwent SPAPS method (n=37) and SS method (n=29) from 2015 to 2019 at single institution were concluded in this study. The pre- and post-operative changes in the following were compared retrospectively between the two groups: surgical factors and clinical evaluations including JOA back pain evaluation questionnaire (JOABPEQ), visual analogue scale (VAS) on lower back pain, buttock/lower limb pain, and buttock/lower limb numbness, and Roland-Morris disability questionnaire (RDQ). <br/>
Results<br/>
The SPAPS method was able to significantly reduce the surgical time (p=0.0025) compared to the SS method, and allowed a reduction of approximately 24.4 minutes per segment. The estimated blood loss were similar in both groups, and with regards to post-operative outcomes, both groups improved equally well. The rates of screw deviation and fusion were also similar. <br/>
Conclusions<br/>
In the case of performing the combined anterior-posterior surgery under a single position, the anterior and posterior procedure can be performed independently and simultaneously by two spine surgeons by utilizing the 3D fluoroscopy-based navigation. The surgical time can be significantly reduced by approximately 24.4 minutes per segment comparing to the SS method.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama107814393932021Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review180190ENEkaterinaLaukhtinaDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaBenjaminPradereDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaKeiichiroMoriDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaVictor M.SchuettfortDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaFahadQuhalDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaHadiMostafaeiDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaRezaSari MotlanghDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaSatoshiKatayamaDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNico C.GrossmannDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaMarcoMoschiniDepartment of Urology, Luzerner KantonsspitalDmitryEnikeevInstitute for Urology and Reproductive Health, Sechenov University,Shahrokh F.ShariatDepartment of Urology, Comprehensive Cancer Center, Medical University of ViennaPURPOSE<br/>
The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). <br/>
MATERIAL AND METHODS<br/>
The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. <br/>
RESULTS<br/>
Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 – gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two – next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. <br/>
CONCLUSION<br/>
We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama246864412021Low-Angle Patent Foramen Ovale (PFO): High-Risk PFO Morphology Associated with Paradoxical EmbolismENRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTeijiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNorihisaTohDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1044579X2021Cooperation between NRF2-mediated transcription and MDIG-dependent epigenetic modifications in arsenic-induced carcinogenesis and cancer stem cellsENZhuoyueBiDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityQianZhangDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityYaoFuDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityAkimasaSenoFaculty of Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPriyaWadgaonkarDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityYiranQiuDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityBandarAlmutairyDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityLipingXuDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityWenxuanZhangDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityChitraThakurDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State UniversityFeiChenDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University Environmental exposure to arsenic, a well-established carcinogen linked to a number of human cancers, is a public health concern in many areas of the world. Despite extensive studies on the molecular mechanisms of arsenic-induced carcinogenesis, how initial cellular responses, such as activation of stress kinases and the generation of reactive oxygen species, converge to affect the transcriptional and/or epigenetic reprogramming required for the malignant transformation of normal cells or normal stem cells remains to be elucidated. In this review, we discuss some recent discoveries showing how the transcription factor NRF2 and an epigenetic regulator, MDIG, contribute to the arsenic-induced generation of cancer stem-like cells (CSCs) as determined by applying CRISPR-Cas9 gene editing and chromosome immunoprecipitation followed by DNA sequencing (ChIP-seq).No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama09609776562021Prospective cohort study of febrile neutropenia in breast cancer patients administered with neoadjuvant and adjuvant chemotherapies: CSPOR-BC FN study7077ENTakashiIshikawaDepartment of Breast Surgery and Oncology, Tokyo Medical UniversityKentaroSakamakiDepartment of Biostatistics, Yokohama City UniversityKazutakaNaruiDepartment of Biostatistics, Yokohama City UniversityHidekiNishimuraDepartment of Biostatistics, Yokohama City UniversityTakafumiSangaiDepartment of Breast and Thyroid Surgery, Chiba UniversityKentaroTamakiNaha-Nishi ClinicYoshieHasegawaDepartment of Breast Surgery, Hirosaki Municipal HospitaKen-ichiWatanabeDepartment of Breast Surgery, Hokkaido Cancer CenterNobuyasuSuganumaDepartment of Breast and Thyroid Surgery, Kanagawa Cancer CenterShintaroMichishitaDepartment of Breast Surgery, Yao Municipal HospitalSadatoshiSugaeDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of MedicineTomohikoAiharaBreast Center, Aihara HospitalKoichiroTsugawaDepartment of Breast and Thyroid Surgery, St. Marianna UniversityHiroseKaiseDepartment of Breast Surgery and Oncology, Tokyo Medical UniversityNarutoTairaDepartment of Breast and Endocrinology Surgery, Okayama University Graduate School of MedicineHirofumiMukaiDivision of Oncology/Hematology, National Cancer Center Hospital EastBackground<br/>
As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). <br/>
Patients and methods<br/>
Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians’ discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. <br/>
Results<br/>
Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. <br/>
Conclusions<br/>
FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama092552141742020Combined signal sequence trap and macroarray analysis identifies genes associated with differential fruit softening characteristics during ripening in European and Chinese pears111436ENMercy W.MwanikiGraduate School of Environmental and Life Science, Okayama UniversityOscar W.MitaloGraduate School of Environmental and Life Science, Okayama UniversityEric G.MworiaGraduate School of Environmental and Life Science, Okayama UniversityWillis O.OwinoGraduate School of Environmental and Life Science, Okayama UniversityKyokoHiwasa-TanaseGraduate School of Life and Environmental Sciences, University of TsukubaJocelyn K.C.RosePlant Biology Section, School of Integrative Plant Science, Cornell UniversityKohAokiGraduate School of Life and Environmental Sciences, Osaka Prefecture UniversityTomoyaEsumiAcademic Assembly Institute of Agricultural and Life Sciences, Shimane UniversityTakashiKawaiGraduate School of Environmental and Life Science, Okayama UniversityRyoheiNakanoGraduate School of Environmental and Life Science, Okayama UniversityKoichiroUshijimaGraduate School of Environmental and Life Science, Okayama UniversityYasutakaKuboGraduate School of Environmental and Life Science, Okayama University During ripening, European pear (Pyrus communis L. cv. ‘La France’) fruit undergo dramatic softening in response to increased ethylene production, whereas Chinese pear (Pyrus bretschneideri Rehd. cv. ‘Yali’) fruit remain firm, despite producing large amounts of ethylene. The molecular basis of this differential softening behavior is not well understood. In this study, we combined a yeast-based signal sequence trap (YSST) and macroarray gene expression analysis to identify putative genes encoding secreted proteins that control pear fruit softening. We identified 22 cDNAs annotated as encoding proteins with diverse cell wall-associated functions that were up- or down-regulated during fruit ripening in ‘La France’. Gene expression analysis in fruit that were treated with the ethylene perception inhibitor 1-methylcyclopropene (1-MCP) at 4 d after the onset of ripening revealed that 16 of the targeted genes are ethylene-regulated, while the others appear to be ethylene independent. Comparative gene expression analyses of ‘La France’ and ‘Yali’ fruit during ripening suggested that four ethylene-regulated cDNAs encoding cell wall modifying proteins, contig 2 (polygalacturonase 3), contig 15 (expansin), contig 19 (expansin) and contig 55 (pectate lyase) contribute to the different softening behaviors of ‘La France’ and ‘Yali’ fruit. Additionally, one ethylene-independent cell wall related gene, contig 36 (expansin), and three genes encoding proteins of unknown function, contigs 1, 13 and contig 75 showed differential expression between ‘La France’ and ‘Yali’ fruit during ripening. The results presented herein represent promising candidates for future functional analysis and elucidation of softening mechanisms.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003808066122021Reliability-based design for earth-fill dams against severe natural disaster events271282ENShin-ichiNishimuraGraduate School of Environmental and Life Science, Okayama UniversityToshifumiShibataGraduate School of Environmental and Life Science, Okayama UniversityTakayukiShukuGraduate School of Environmental and Life Science, Okayama UniversityThe maintenance of geotechnical structures, such as earth-fill dams, is required as a countermeasure against severe natural disasters, particularly earthquakes and heavy rains. The reliability-based analysis introduced here is in response to the recent demand for low-cost improvements.First, a statistical model of N values was determined from Swedish weight sounding (SWS) tests to present the spatial variability of the soil strength. Then, a reliability-based analysis of embankments was conducted by considering the variability of the internal friction angle derived from N value, and the seismic hazard for the Nankai Trough. The next step was to evaluate the probability of the overflow of earth-fills during heavy rains. The rainfall intensity was considered as a probabilistic parameter, and the various rainfall patterns were tested by the proposed method. Finally, the total risk due to both earthquakes and heavy rains was evaluated for an earth-fill site. As a result, the possibility for the practical use of the proposed method in making plans for the maintenance of deteriorated earth-fill dams was verified.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama002235491102021Lactosome-Conjugated siRNA Nanoparticles for Photo-Enhanced Gene Silencing in Cancer Cells17881798ENMelissa Siaw HanLimYukiNishiyamaTakashiOhtsukiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazunoriWatanabeGraduate School of Natural Science and Technology, Okayama UniversityHirotsuguKobuchiKazukoKobayashiCollaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiMatsuuraThe A3B-type Lactosome comprised of poly(sarcosine)3-block-poly(l-lactic acid), a biocompatible and biodegradable polymeric nanomicelle, was reported to accumulate in tumors in vivo via the enhanced permeability and retention (EPR) effect. Recently, the cellular uptake of Lactosome particles was enhanced through the incorporation of a cell-penetrating peptide (CPP), L7EB1. However, the ability of Lactosome as a drug delivery carrier has not been established. Herein, we have developed a method to conjugate the A3B-type Lactosome with ATP-binding cassette transporter G2 (ABCG2) siRNA for inducing in vitro apoptosis in the cancer cell lines PANC-1 and NCI-H226. The L7EB1 peptide facilitates the cellular uptake efficiency of Lactosome but does not deliver siRNA into cytosol. To establish the photoinduced cytosolic dispersion of siRNA, a photosensitizer loaded L7EB1-Lactosome was prepared, and the photosensitizer 5,10,15,20-tetra-kis(pentafluorophenyl)porphyrin (TPFPP) showed superiority in photoinduced cytosolic dispersion. We exploited the combined effects of enhanced cellular uptake by L7EB1 and photoinduced endosomal escape by TPFPP to efficiently deliver ABCG2 siRNA into the cytosol for gene silencing. Moreover, the silencing of ABCG2, a protoporphyrin IX (PpIX) transporter, also mediated photoinduced cell death via 5-aminolevulinic acid (ALA)-mediated PpIX accumulated photodynamic therapy (PDT). The synergistic capability of the L7EB1/TPFPP/siRNA-Lactosome complex enabled both gene silencing and PDT.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2590152452021Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from Trichoderma viride100044ENMasakiKitagawaDepartment of Macromolecular Science, Graduate School of Science, Osaka UniversityNanakoItoDepartment of Macromolecular Science, Graduate School of Science, Osaka UniversityYuyaMatsumotoDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityMasayaSaitoDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityTakashiTamuraDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityHitoshiKusakabeEnzyme Sensor Co., Ltd.KenjiInagakiDepartment of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama UniversityKatsumiImadaDepartment of Macromolecular Science, Graduate School of Science, Osaka UniversityHarmuful proteins are usually synthesized as inactive precursors and are activated by proteolytic processing. l-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of l-amino acid to produce a 2-oxo acid with ammonia and highly toxic hydrogen peroxide and, therefore, is expressed as a precursor. The LAAO precursor shows significant variation in size and the cleavage pattern for activation. However, the molecular mechanism of how the propeptide suppresses the enzyme activity remains unclear except for deaminating/decarboxylating Pseudomonasl-phenylalanine oxidase (PAO), which has a short N-terminal propeptide composed of 14 residues. Here we show the inactivation mechanism of the l-lysine oxidase (LysOX) precursor (prLysOX), which has a long N-terminal propeptide composed of 77 residues, based on the crystal structure at 1.97 Å resolution. The propeptide of prLysOX indirectly changes the active site structure to inhibit the enzyme activity. prLysOX retains weak enzymatic activity with strict specificity for l-lysine and shows raised activity in acidic conditions. The structures of prLysOX crystals that soaked in a solution with various concentrations of l-lysine have revealed that prLysOX can adopt two conformations; one is the inhibitory form, and the other is very similar to mature LysOX. The propeptide region of the latter form is disordered, and l-lysine is bound to the latter form. These results indicate that prLysOX uses a different strategy from PAO to suppress the enzyme activity and suggest that prLysOX can be activated quickly in response to the environmental change without proteolytic processing.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama002192582962021Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor100524ENKengoNakaharaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKyoheiHamadaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokiTsuchidaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNobumasaTakasugiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYumiAbikoEnvironmental Biology Laboratory, Faculty of Medicine, University of TsukubaKazuhikoShienDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartment of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshitoKumagaiEnvironmental Biology Laboratory, Faculty of Medicine, University of TsukubaTakashiUeharaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThe epidermal growth factor receptor (EGFR) is the most intensively investigated receptor tyrosine kinase. Several EGFR mutations and modifications have been shown to lead to abnormal self-activation, which plays a critical role in carcinogenesis. Environmental air pollutants, which are associated with cancer and respiratory diseases, can also activate EGFR. Specifically, the environmental electrophile 1,2-naphthoquinone (1,2-NQ), a component of diesel exhaust particles and particulate matter more generally, has previously been shown to impact EGFR signaling. However, the detailed mechanism of 1,2-NQ function is unknown. Here, we demonstrate that 1,2-NQ is a novel chemical activator of EGFR but not other EGFR family proteins. We found that 1,2-NQ forms a covalent bond, in a reaction referred to as N-arylation, with Lys80, which is in the ligand-binding domain. This modification activates the EGFR–Akt signaling pathway, which inhibits serum deprivation–induced cell death in a human lung adenocarcinoma cell line. Our study reveals a novel mode of EGFR pathway activation and suggests a link between abnormal EGFR activation and environmental pollutant–associated diseases such as cancer.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama091450877812020Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats1216ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesLuh Oliva SaraswatiSuastikaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiroHigashimotoDepartment of Chemistry, Kurume University School of MedicineKeiFukamiDivision of Nephrology, Department of Medicine, Kurume University School of MedicineHiromiMatsubaraDepartment of Cardiology, National Hospital Organization Okayama Medical CenterHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: The receptor for advanced glycation end products (RAGE), a transmembrane receptor belonging to the immunoglobulin superfamily, is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with pulmonary arterial hypertension (PAH) and is implicated in the etiology of PAH. Recently, we reported that RAGE-aptamer, a short and single-stranded DNA directed against RAGE, inhibited an inappropriate increase in cultured PASMCs in PAH. The aim of this study was to determine the efficacy of RAGEaptamer in monocrotaline-induced PAH in rats.<br><br>
Methods and Results: Rats were assigned to either an untreated control group, a group that received continuous subcutaneous administration of RAGE-aptamer immediately after monocrotaline injection, or a group that received control-aptamer immediately after monocrotaline injection. All rats survived 21 days after injection of monocrotaline and control-aptamer or RAGE-aptamer. Injection of monocrotaline with continuous subcutaneous delivery of control-aptamer resulted in higher right ventricular systolic pressure compared with controls. This increase was attenuated by continuous subcutaneous delivery of RAGE-aptamer. The proportion of small pulmonary arteries with full muscularization was greater in the monocrotaline and control-aptamer group than in the control group. Continuous subcutaneous delivery of RAGE-aptamer significantly reduced the percentage of small pulmonary arteries with full muscularization Conclusions: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of 3 small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for PAH.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0019-10353592021Salt – A critical material to consider when exploring the solar system114328ENM.R.M.IzawaInstitute for Planetary Materials, Okayama UniversityP.L.KingResearch School of Earth Sciences, Australian National University CanberraP.VernazzaLab. d'Astrophys. de Marseille, Pôle de l'EtoileJ.A.BergerInst. Meteoritics, Univ. New MexicoW.A.McCutcheonInst. Meteoritics, Univ. New MexicoSalt-rich deposits may be more widespread on planetary surfaces than is generally appreciated. Remote observations, laboratory studies of meteorites, and cosmochemical constraints all point towards widespread occurrences of salts (including halides, sulfates, and (bi)carbonates) on asteroids, icy bodies, Mars, and elsewhere. We have investigated the mid-infrared (1.8–25 μm) reflectance spectral properties of mixtures of chondritic (ordinary, enstatite and carbonaceous) meteorites with potassium bromide; a mid-infrared transmissive salt like all halides. Our results demonstrate that halide-chondrite mixtures provide spectral signatures that either reveal the presence of transmissive materials or provide evidence for highly porous regolith. Previously, the nature of the surfaces of the asteroids 624 Hektor and 21 Lutetia was inferred using a limited range of spectra from halide-chondrite mixtures. Here, we provide an extensive dataset of halide-chondrite mixtures to encompass a wider set of possible surface compositions.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-50938072021Effects of microstructural characteristics on the hydrogen embrittlement characteristics of austenitic, ferritic, and γ–α duplex stainless steels140851ENMitsuhiroOkayasuGraduate School of Natural Science and Technology, Okayama UniversityTakafumiFujiwaraGraduate School of Natural Science and Technology, Okayama UniversityHydrogen embrittlement (HE) characteristics of γ (AS), α (FS), and γ–α duplex (DS) stainless steels were examined experimentally and numerically. Severe HE occurred in the DS sample, whereas weak HE was detected in the AS and FS samples. This was attributed to the high hydrogen concentrations at the DS-trapping sites. Hydrogen trapping occurred in the low atomic density zones in the boundaries between α and γ phases in DS sample. The chemical bonding between atomic-scale phase boundaries was weakened by hydrogen penetration. This resulted in a crack growth along the DS α/γ phase boundaries. The ductility of DS decreased as the hydrogen content increased, especially when it exceeded 15 ppm. In contrast, the weak HE observed among AS and FS samples was attributed to the small hydrogen levels that infiltrated both samples. Finally, HE mechanism was proposed on the basis of these experimental results.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2212-62871012021Pullout Repair Associated With a Bridging Suture Using FiberLink for the Medial Meniscus Posterior Horn/Root Teare91e95ENTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University HospitalTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University HospitalTranstibial pullout repair for the medial meniscus (MM) posterior root tear has become the gold standard. However, an optimal repair technique has not yet been established for MM posterior horn (MMPH) tear with a sufficient root remnant. We describe a pullout repair technique associated with a bridging suture using FiberLink (Arthrex, Naples, FL) for the MMPH tear. In this bridging suture technique, the simple cinch stitch is applied to the root remnant and MMPH. The loop end of the FiberLink is inserted into the MMPH, and its free-end is inserted into the root remnant. Next, the suture is tensioned and tied on the superior surface of the MMPH. The bridging suture and the additional simple stitch applied to the MMPH are pulled out through the tibial tunnel and fixed to the tibia on an expected tension. This technique might lead to better meniscal healing of the tear site, because it involves bridging of the MMPH and root remnant, and lower risk of suture cut-out owing to the biomechanical strength.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2468-8673202021The sweet taste receptor, glucose transporters, and the ATP-sensitive K+ (KATP) channel: sugar sensing for the regulation of energy homeostasis5763ENRyusukeYoshidaDepartment of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeikoYasumatsuTokyo Dental Junior CollegeYuzoNinomiyaDivision of Sensory Physiology and Medical Application Sensing, Research and Development Center for Five-Sense Devices, Kyushu UniversitySugar detection in the oral cavity does not solely depend on the TAS1R2 + TAS1R3 sweet receptor. Similar to gut, pancreas, and hypothalamic neurons, in the tongue glucose transporters and ATP-sensitive K+ (KATP) channels are also involved in sugar detection. Among them, the KATP channel is the target for the antiobesity hormone leptin, which inhibits sugar-sensitive cells such as sweet taste cells, pancreatic β-cells, and hypothalamic orexigenic neurons. Sugar signals from the taste organ elicit cephalic-phase insulin release, and those from the gut contribute to sweet preference for caloric sugars. All of these systems are indispensable for maintaining energy homeostasis. Thus, an exquisite system for sugar detection/signaling to regulate energy homeostasis exists in our body.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0914-50877712021Transcatheter closure of patent foramen ovale: Current evidence and future perspectives39ENTeijiAkagiDepartment of Cardiovascular Medicine, Okayama UniversityRecent prospective controlled studies have demonstrated that transcatheter closure of a patent foramen ovale (PFO) reduces recurrent stroke risk in select patients, especially in patients younger than 60 years with PFO and embolic-appearing infarct and where no other mechanism of stroke was identified. Detection of PFO depends on the intensity of the Valsalva maneuver, and not all PFOs can be diagnosed using transesophageal echocardiography. Transthoracic contrast echocardiography using abdominal compression during the Valsalva maneuver is an easy method that can increase the detection sensitivity of PFO shunt. PFO with two or more of the following factors is most likely considered a “high-risk PFO” and as such, has a significantly higher probability of cryptogenic stroke: (1) a long-tunnel PFO (≥10 mm in length), (2) atrial septal aneurysm and/or hypermobile interatrial septum, (3) prominent Eustachian valve or Chiari’s network, (4) large right-to-left shunt at rest and during the Valsalva maneuver, and (5) low-angle PFO. In order to establish the benefit of catheter-based PFO closure as a safe and effective treatment in clinical practice, the degree of accuracy of PFO diagnosis and its long-term safety need to be confirmed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1387-70031242021Effect of ultrasonic irradiation on γ-Fe2O3 formation by co-precipitation method with Fe3+ salt and alkaline solution108400ENHayatoKoizumiDepartment of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityMd. AzharUddinDepartment of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityYoshieiKatoDepartment of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityThe effect of ultrasonic irradiation on direct maghemite (γ-Fe2O3) preparation by a co-precipitation method with Fe3+ salt (Fe(NO3)3) and an excess amount of alkaline (KOH) solution without going through the conventional magnetite (Fe3O4) formation route was explored in comparison with impeller stirring. The preparation procedure for obtaining iron oxide nanoparticles was designed using the sequential processes of precipitation, decantation, drying and thermal dehydration, and ultrasonic irradiation or impeller stirring was done during the precipitation process. γ-ferric oxyhydroxide (γ-FeOOH) was partially formed in addition to α-ferric oxyhydroxide (α-FeOOH) and thermally dehydrated to γ-Fe2O3 and hematite (α-Fe2O3) by ultrasonic-assisted co-precipitation of Fe3+ salt and the excess KOH solution, whereas only α-FeOOH and α-Fe2O3 were synthesized by impeller stirring. The difference between the products of the two methods was explained by the Lamer model associated with the nucleation and growth of FeOOH. Magnetization increased as the crystallite diameter decreased, which is estimated to facilitate partial formation of magnetic γ-Fe2O3. Magnetization was enhanced by a lower ultrasonic frequency due to the stronger shock wave induced by the cavitation effect.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0167-63931262021Model architectures to extrapolate emotional expressions in DNN-based text-to-speech3543ENKatsukiInoueGraduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySunaoHaraGraduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasanobuAbeGraduate school of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNobukatsuHojoNTT CorporationYusukeIjimaNTT CorporationThis paper proposes architectures that facilitate the extrapolation of emotional expressions in deep neural network (DNN)-based text-to-speech (TTS). In this study, the meaning of “extrapolate emotional expressions” is to borrow emotional expressions from others, and the collection of emotional speech uttered by target speakers is unnecessary. Although a DNN has potential power to construct DNN-based TTS with emotional expressions and some DNN-based TTS systems have demonstrated satisfactory performances in the expression of the diversity of human speech, it is necessary and troublesome to collect emotional speech uttered by target speakers. To solve this issue, we propose architectures to separately train the speaker feature and the emotional feature and to synthesize speech with any combined quality of speakers and emotions. The architectures are parallel model (PM), serial model (SM), auxiliary input model (AIM), and hybrid models (PM&AIM and SM&AIM). These models are trained through emotional speech uttered by few speakers and neutral speech uttered by many speakers. Objective evaluations demonstrate that the performances in the open-emotion test provide insufficient information. They make a comparison with those in the closed-emotion test, but each speaker has their own manner of expressing emotion. However, subjective evaluation results indicate that the proposed models could convey emotional information to some extent. Notably, the PM can correctly convey sad and joyful emotions at a rate of >60%.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0260-87742922021Crystallization characteristics of amorphous trehalose dried from alcohol110325ENTakanariSekitohDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityTakashiOkamotoDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityAkihoFujiokaDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityTomohikoYoshiokaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShinjiTeruiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHiroyukiImanakaDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityNaoyukiIshidaDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityKoreyoshiImamuraDivision of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama UniversityTrehalose forms a glass that can be used to preserve labile substances under desiccation. The crystallization characteristics, namely crystallization temperature (Tcry) and isothermal crystallization behavior of amorphous trehalose, dried from alcohol (methanol, ethanol), was analyzed and the results were compared with those for the amorphous trehalose freeze-dried from water. The use of alcohol as a solvent lowered the Tcry from 184 ± 6 °C for the case of an aqueous solvent to 103 ± 5 °C/methanol and 120 ± 8 °C/ethanol. The formation of multiple forms of crystals and partial melting were suggested by the thermal analysis. Isothermal crystallization experiments showed that the alcohol-originated amorphous trehalose was eventually exclusively converted into β-form crystals. The induction period (tind) before the start of isothermal crystallization was markedly shortened when alcohol was used as the solvent compared to water. The tind values for various amorphous sugar samples including the alcohol-originated ones could be correlated with difference between Tcry and the sample temperature.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1936-52331412021PRRX1 promotes malignant properties in human osteosarcoma100960ENRyojiJokoDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeYamadaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroNakamuraPrecision Health, Department of Bioengineering, Graduate School of Engineering, The University of TokyoAkiYoshidaDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShotaTakihiraDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokaTakaoDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMingLuDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiSatoDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTatsuoItoDepartment of Hygiene, Kawasaki Medical SchoolToshiyukiKunisadaDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEijiNakataDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakeshiTakaradaDepartment of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesPaired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0304-38354972021Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis13ENHirokiKajiokaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShunsukeKagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAteneItoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshimotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiSakamotoDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruKikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroNomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiTazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSurgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-76165612020Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation119126ENTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesCellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-84406122020Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factorse05743ENWen TanXianDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazukoKobayashiCollaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShenLianhuaDepartment of Pathophysiology, Zunyi Medical UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasahiroIdeDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSiaw SanHwangSchool of Chemical Engineering and Science, Faculty of Engineering, Computing and Science, Swinburne University of Technology Sarawak CampusEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1β, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/β2-glycoprotein I (oxLDL/β2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr−/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1β) and hepatic (TNF-α, IL-1α, IL-1β) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1387-18113042020Mineralogical alterations in calcite powder flooded with MgCl2 to study Enhanced Oil Recovery (EOR) mechanisms at pore scale109402ENMona W.MindeThe National IOR Centre of NorwayMerete V.MadlandThe National IOR Centre of NorwayUdoZimmermannThe National IOR Centre of NorwayNinaEgelandThe National IOR Centre of NorwayReidar I.KorsnesThe National IOR Centre of NorwayEizoNakamuraInstitute for Planetary Materials, Okayama UniversityKatsuraKobayashiInstitute for Planetary Materials, Okayama UniversityTsutomuOtaInstitute for Planetary Materials, Okayama UniversitySeawater injection into chalk-reservoirs on the Norwegian Continental Shelf has increased the oil recovery and reduced seabed subsidence, but not eliminated it. Therefore, understanding rock–fluid interactions is paramount to optimize water injection, predict and control water-induced compaction.</br>
Laboratory experiments on onshore and reservoir chalks have shown the need to simplify the aqueous chemistry of the brine, and also the importance of studying the effect of primary mineralogy of chalk to understand which ions interact with the minerals present. In this study, the mineralogy of the samples tested, are simplified. These experiments are carried out on pure calcite powder (99.95%), compressed to cylinders, flooded with MgCl2, at 130 °C and 0.5 MPa effective stress, for 27 and 289 days.</br>
The tested material was analysed by scanning and transmission electron microscopy, along with whole-rock geochemistry. The results show dissolution of calcite followed by precipitation of magnesite. The occurrence and shape of new-grown crystals depend on flooding time and distance from the flooding inlet of the cylinder. Crystals vary in shape and size, from a few nanometres up to 2 μm after 27 days, and to over 10 μm after 289 days of flooding and may crystallize as a single grain or in clusters.</br>
The population and distribution of new-grown minerals are found to be controlled by nucleation- and growth-rates along with advection of the injected fluid through the cores. Our findings are compared with in-house experiments on chalks, and allow for insight of where, when, and how crystals preferentially grow.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2451-8654192020HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema100595ENShinsukeAkitaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of MedicineNaokiUnnoDepartment of Vascular Surgery, Hamamatsu Medical CenterJiroMaegawaDepartment of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of MedicinYoshihiroKimataDepartment of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHidekazuFukamizuDepartment of Plastic and Reconstructive Surgery, Hamamatsu University School of MedicineYuichiroYabukiDepartment of Plastic and Reconstructive Surgery, Yokohama City University, Graduate School of MedicineAkiraShinaokaDepartment of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasakiSanoSecond Department of Surgery, Hamamatsu University School of MedicineYoheiKawasakiClinical Research Center, Chiba University HospitalTadamiFujiwaraClinical Research Center, Chiba University HospitalHidekiHanaokaClinical Research Center, Chiba University HospitalNobuyukiMitsukawaDepartment of Plastic, Reconstructive, and Aesthetic Surgery, Chiba University Graduate School of MedicineIntroduction</br>
Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery.</br>
Methods and analysis</br>
This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA.</br>
Ethics and dissemination</br>
The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0960-98223112020Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord103114.e5ENTakumiOtiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityKeitaSatohUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityDaisukeUtaDepartment of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of ToyamaJuntaNagafuchiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversitySayakaTateishiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityRyotaUedaUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityKeikoTakanamiUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityLarry J.YoungCenter for Translational Social Neuroscience, Silvio O. Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory UniversityAntonyGalioneDepartment of Pharmacology, University of OxfordJohn F.MorrisDepartment of Physiology, Anatomy & Genetics, University of OxfordTatsuyaSakamotoUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityHirotakaSakamotoUshimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama UniversityOxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion—a localized volume transmission—to reach oxytocin receptors on GRP neurons and facilitate male sexual function.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X26102020Concomitant vancomycin and piperacillin/tazobactam treatment is associated with an increased risk of acute kidney injury in Japanese patients10261032ENYutoHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaiHarukiDepartment of Pharmacy, Tsuyama Chuo HospitalYutaInoueDepartment of Pharmacy, Tsuyama Chuo HospitalTetsuhiroSugiyamaDepartment of Pharmacy, Tsuyama Chuo HospitalIntroduction</br>
Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy).</br>
Methods</br>
The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients’ baseline hospital admittance status, as intensive care unit or general wards.</br>
Results</br>
We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02).</br>
Conclusion</br>
VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0269-74912692020Cadmium transfer in contaminated soil-rice systems: Insights from solid-state speciation analysis and stable isotope fractionation115934ENMatthiasWiggenhauserUniv. Grenoble AlpesAnne-MarieAucourUniversité de LyonSarahBureauUniv. Grenoble AlpesSylvainCampilloUniv. Grenoble AlpesPhilippeTeloukUniversité de LyonMarcoRomaniCentro Ricerche sul Riso, Ente Nazionale Risi, Strada per CerettoJian FengManstitute of Plant Science and Resources, Okayama UniversityGautierLandrotSynchrotron SOLEIL, L’Ormes des MerisiersGéraldineSarretUniv. Grenoble AlpesInitial Cadmium (Cd) isotope fractionation studies in cereals ascribed the retention of Cd and its light isotopes to the binding of Cd to sulfur (S). To better understand the relation of Cd binding to S and Cd isotope fractionation in soils and plants, we combined isotope and XAS speciation analyses in soil-rice systems that were rich in Cd and S. The systems included distinct water management (flooded vs. non-flooded) and rice accessions with (excluder) and without (non-excluder) functional membrane transporter OsHMA3 that transports Cd into root vacuoles. Initially, 13% of Cd in the soil was bound to S. Through soil flooding, the proportion of Cd bound to S increased to 100%. Soil flooding enriched the rice plants towards heavy isotopes (δ114/110Cd = −0.37 to −0.39%) compared to the plants that grew on non-flooded soils (δ114/110Cd = −0.45 to −0.56%) suggesting that preferentially light Cd isotopes precipitated into Cd sulfides. Isotope compositions in CaCl2 root extracts indicated that the root surface contributed to the isotope shift between soil and plant during soil flooding. In rice roots, Cd was fully bound to S in all treatments. The roots in the excluder rice strongly retained Cd and its lights isotopes while heavy isotopes were transported to the shoots (Δ114/110Cdshoot-root 0.16–0.19‰). The non-excluder rice accumulated Cd in shoots and the apparent difference in isotope composition between roots and shoots was smaller than that of the excluder rice (Δ114/110Cdshoot-root −0.02 to 0.08‰). We ascribe the retention of light Cd isotopes in the roots of the excluder rice to the membrane transport of Cd by OsHMA3 and/or chelating Cd–S complexes in the vacuole. Cd–S was the major binding form in flooded soils and rice roots and partly contributed to the immobilization of Cd and its light isotopes in soil-rice systems.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-36593302020Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT)788196ENHiroyukiMichiueNeutron Therapy Research Center, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityAsamiFukunagaDepartment of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobushigeTsuboiDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAtsushiFujimuraDepartment of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroakiMatsushitaDepartment of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuyoIgawaNeutron Therapy Research Center, Okayama UniversityTomonariKasaiNeutron Therapy Research Center, Okayama UniversityNatsukoKondoInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityHidekiMatsuiNeutron Therapy Research Center, Okayama UniversityShuichiFuruyaNeutron Therapy Research Center, Okayama UniversityBoron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies—determined by electron microscopy—and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-76165612020Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation119126ENTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesCellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1882-76165612020Evaluation of dental caries, tooth crack, and age-related changes in tooth structure using optical coherence tomography109118ENYasushiShimadaDepartment of Operative Dentistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasahiroYoshiyamaDepartment of Operative Dentistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJunjiTagamiDepartment of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental UniversityYasunoriSumiDepartment for Advanced Dental Research, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and GerontologyOptical coherence tomography (OCT) is an imaging technique that can visualize the internal biological structure without X-ray exposure. Swept-source OCT (SS-OCT) is one of the latest version of OCT, wherein the light source is a tunable laser that sweeps near-infrared wavelength light to achieve real-time imaging. The imaging depth of OCT is highly influenced by the translucency of the medium. The medium that does not transmit light and the deeper structure beyond the range of light penetration depth are not relevant for OCT imaging. In OCT, sound enamel is almost transparent at the OCT wavelength range, and enamel and dentin can be distinguished from each other as the dentin–enamel junction (DEJ) appears as a dark border. Demineralized enamel and dentin are imaged as bright zones because of the formation of numerous micro-porosities where the backscatter of OCT signal is increased. In cavitated caries at interproximal or occlusal hidden zone, the upper margin of the cavity reflects the signal showing a distinct bright border in the SS-OCT image. SS-OCT is capable of determining crack penetration depth even when the cracks extended beyond the DEJ. SS-OCT has a high degree of sensitivity and specificity for the detection of dental caries and tooth cracks. SS-OCT is also capable of detecting non-carious cervical lesions and occlusal tooth wear in cross-sectional views to estimate the amount of tooth structure loss.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0169-50021492020Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study4652ENJonathan W.GoldmanDavid Geffen School of Medicine at UCLAMarina ChiaraGarassinoFondazione IRCCS Istituto Nazionale dei TumoriYuanbinChenCancer & Hematology Centers of Western MichiganMustafaÖzgüroğluIstanbul University–Cerrahpaşa, Cerrahpaşa School of MedicineMikhailDvorkinBHI of Omsk Region Clinical Oncology DispensaryDmytroTrukhinOdessa National Medical UniversityGalinaStatsenkoOmsk Regional Cancer Center,KatsuyukiHottaOkayama University HospitalJun HoJiSamsung Changwon Hospital, Sungkyunkwan University School of MedicineMaximilian J.HochmairKarl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik FloridsdorfOleksandrVoitkoKyiv City Clinical Oncological CentreLiborHavelThomayer Hospital, First Faculty of Medicine, Charles UniversityArtemPoltoratskiyPetrov Research Institute of OncologyGyörgyLosonczySemmelweis UniversityNielsReinmuthAsklepios Lung ClinicNikunjPatelAstraZenecaPeter J.LaudStatistical Services Unit, University of SheffieldNorahShireAstraZenecaHaiyiJiangAstraZenecaLuisPaz-AresHospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and CiberoncObjectives</br>
In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs).</br>
Materials and methods</br>
Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed.</br>
Results</br>
In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, −4.5; 99% CI: −9.04, −0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL.</br>
Conclusion</br>
Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2589-5370282020Impact of patient characteristics on the efficacy and safety of landiolol in patients with sepsis-related tachyarrhythmia: Subanalysis of the J-Land 3S randomised controlled study100571ENNaoyukiMatsudaDepartment of Emergency & Critical Care Medicine, Nagoya University Graduate School of MedicineOsamuNishidaDepartment of Anesthesiology & Critical Care Medicine, Fujita Health University School of MedicineTakumiTaniguchiDepartment of Anesthesiology & Intensive Care Medicine, Kanazawa UniversityMasakiOkajimaIntensive Care Unit, Kanazawa University HospitalHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiOguraDepartment of Traumatology and Acute Critical Medicine, Osaka University Graduate School of MedicineYoshitsuguYamadaDepartment of Anesthesiology and Pain Relief Center, The University of Tokyo HospitalTetsujiNaganoClinical Development Planning, Ono Pharmaceutical Co., Ltd.AkiraIchikawaClinical Development Planning, Ono Pharmaceutical Co., Ltd.YasuyukiKakihanaDepartment of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental SciencesJ-Land 3S Study GroupBackground</br>
The J-Land 3S trial demonstrated that landiolol is effective and tolerated for treating sepsis-related tachyarrhythmias. Patient characteristics (e.g. baseline heart rate [HR], type of tachyarrhythmia, and concomitant disorders) may impact the outcomes of landiolol therapy. We performed subanalyses of J-Land 3S to evaluate the impact of patient characteristics on the efficacy and safety of landiolol for treating sepsis-related tachyarrhythmia.</br>
Methods</br>
Patients (≥20 years old; N = 151) hospitalised with sepsis at 54 participating hospitals in Japan with HR ≥100 beats/min for ≥10 min accompanied by diagnosis of tachyarrhythmia were randomised 1:1 to conventional sepsis therapy alone (control group) or conventional sepsis therapy plus landiolol (landiolol group). The efficacy and safety of landiolol were assessed in prespecified analyses of patients divided into subgroups by baseline characteristics and in post hoc, multivariate analyses with adjustment for age and HR at baseline.</br>
Findings</br>
The percentage of patients with HR of 60–94 beats/min at 24 h after randomisation (primary endpoint) was greater in the landiolol group in most subgroups in univariate unadjusted analyses and in multivariate logistic regression. The incidence of new-onset arrhythmia by 168 h and mortality by 28 days were also lower in the landiolol group in most subgroups in univariate and multivariate Cox proportional hazards models. No subgroups showed a markedly higher incidence of adverse events in univariate or multivariate logistic regression analyses.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0042-68225542021Cryphonectria nitschkei chrysovirus 1 with unique molecular features and a very narrow host range5562ENSabitreeShahiInstitute of Plant Science and Resources, Okayama UniversitySotaroChibaGraduate School of Bioagricultural Sciences, Nagoya UniversityHidekiKondoInstitute of Plant Science and Resources, Okayama UniversityNobuhiroSuzukiInstitute of Plant Science and Resources, Okayama UniversityCryphonectria nitschkei chrysovirus 1 (CnCV1), was described earlier from an ascomycetous fungus, Cryphonectria nitschkei strain OB5/11, collected in Japan; its partial sequence was reported a decade ago. Complete sequencing of the four genomic dsRNA segments revealed molecular features similar to but distinct from previously reported members of the family Chrysoviridae. Unique features include the presence of a mini-cistron preceding the major large open reading frame in each genomic segment. Common features include the presence of CAA repeats in the 5′-untranslated regions and conserved terminal sequences. CnCV1-OB5/11 could be laterally transferred to C. nitschkei and its relatives C. radicalis and C. naterciae via coculturing, virion transfection and protoplast fusion, but not to fungal species other than the three species mentioned above, even within the genus Cryphonectria, suggesting a very narrow host range. Phenotypic comparison of a few sets of CnCV1-infected and -free isogenic strains showed symptomless infection in new hosts.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-48476Suppl. 72020Self-assembly of Ni–Fe layered double hydroxide at room temperature for oxygen evolution reaction248254ENSeong HyunKimDepartment of Materials Science and Engineering, Pusan National UniversityYoo SeiParkDepartment of Materials Science and Engineering, Pusan National UniversityChihoKimDepartment of Materials Science and Engineering, Pusan National UniversityIl YeongKwonDepartment of Materials Science and Engineering, Pusan National UniversityJooyoungLeeMaterials Center for Energy Department, Surface Technology Division, Korea Institute of Materials Science,HyunsooJinDepartment of Mechanical Engineering, Worcester Polytechnic InstituteYoon-SeokLeeGraduate School of Natural Science and Technology, Okayama UniversitySung MookChoiMaterials Center for Energy Department, Surface Technology Division, Korea Institute of Materials ScienceYangdoKimDepartment of Materials Science and Engineering, Pusan National UniversityActive and stable electrocatalysts are the key to water electrolysis for hydrogen production. This paper reports a facile direct growth method to synthesize NiFe-layered double hydroxides (LDHs) on nickel foil as an electrocatalyst for the oxygen evolution reaction. The NiFe-LDH is synthesized by a galvanic process at room temperature without any additional energy for synthesis. The synthesized NiFe-LDH is a karst landform with abundant active sites and efficient mass diffusion. The NiFe-LDH with an oxygen defect show excellent electrocatalytic performance for the OER, with a low overpotential (272 mV at 10 mA/cm2), a small Tafel slope (43 mV/dec), and superior durability. Direct growth synthesis provide excellent electrical conductivity as well as strong bonding between the catalyst layer and the substrate. In addition, this synthesis process is simple to apply in the fabrication of a large size electrode and is believed to be applicable to commercialized alkaline water electrolysis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0377221729312020Optimal Investment under Ambiguous Technology Shocks304311ENTakaoAsanoFaculty of Economics, Okayama UniversityYusukeOsakiFaculty of Commerce, Waseda UniversityThis paper analyzes the behavior of a firm facing an ambiguous technology shock and the effects of the attitude toward ambiguity on optimal capital investment using the smooth ambiguity model of Klibanoffet al. (2005). Although it seems intuitive that an increase in ambiguity aversion always reduces the optimal capital investment, this is not necessarily true because the shape of the production function plays a key role in determining the effect. Under some conditions, we show that the optimal amount of capital investment increases (decreases) in ambiguity aversion if the production function is substitute (complement), and that this result is counterintuitive when the production function is substitute. Furthermore, our main results hold if we assume the alpha-maxmin preferences in Ghirardato et al. (2004). No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0960-9776552020Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer6368ENJunjiTsurutaniAdvanced Cancer Translational Research Institute, Showa UniversityFumikataHaraDepartment of Breast Medical Oncology, Cancer Institute Hospital of JFCRMasahiroKitadaDepartment of Breast Disease Center, Asahikawa Medical University HospitalMasatoTakahashiNHO Hokkaido Cancer CenterYuichiroKikawaDepartment of Breast Surgery, Kobe City Medical Center General HospitaHiroakiKatoTeine Keijinkai HospitalEikoSakataNiigata City General HospitalYoichiNaitoDepartment of Breast and Medical Oncology, National Cancer Center Hospital EastYoshieHasegawaDepartment of Breast Surgery, Hirosaki Municipal HospitalTsuyoshiSaitoJapanese Red Cross Saitama HospitalTsutomuIwasaDepartment of Medical Oncology, Kindai University Faculty of MedicineNarutoTairaOkayama University HospitalTsutomuTakashimaOsaka City University Graduate School of MedicineKosukeKashiwabaraClinical Research Promotion Center, The University of Tokyo HospitalTomohikoAiharaBreast Center, Aihara HospitalHirofumiMukaiNational Cancer Center Hospital East, KashiwaBackground</br>
Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.</br>
Methods</br>
We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.</br>
Results</br>
One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.</br>
Conclusions</br>
Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612762020A novel modified hanging maneuver in laparoscopic left hemihepatectomy251253ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiKuiseDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhiroYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuyaYasuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYumaTaniDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesIntroduction</br>
The liver hanging maneuver is an essential technique for controlling bleeding in hepatectomy, however it is often difficult in laparoscopic major hepatectomy. The present study describes a novel modified hanging maneuver in laparoscopic left hemihepatectomy.</br>
Presentation of case</br>
A 29-year-old female underwent laparoscopic left hemihepatectomy for mucinous cystic neoplasm. After mobilizing the left lobe, the liver parenchyma was dissected along the demarcation line. For the hanging technique, the upper edge of the hanging tape was placed on the lateral side of the left hepatic vein, and fixed with the Falciform ligament. The lower edge of the tape was extracted outside the abdomen. Accordingly the hanging tape can be controlled extraperitoneally during the liver parenchyma dissection.</br>
Discussion</br>
This technique includes several advantages including no need of assistance using forceps, easy control of the hanging tape extraperitoneally, outflow control, better exposure of surgical field, and helpful guide of the liver dissection line toward the root of the left hepatic vein.
Conclusion</br>
Our novel modified hanging maneuver is easy and reproducible to use in laparoscopic left hemihepatectomy. Moreover, this technique can be applied to other laparoscopic hepatectomy.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1349-00796242020Construction and characterization of the PGN_0296 mutant of Porphyromonas gingivalis322326ENAbu Saleh MuhammadShahriarDepartment of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShintaroOnoDepartment of Periodontal Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaakiNakayamaDepartment of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokoOharaDepartment of Operative Dentistry, Okayama University Hospital, Okayama UniversityNaoyaOharaDepartment of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe periodontal pathogen Porphyromonas gingivalis produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in the organism's virulence, and pigmentation. We previously showed that deletion of the PGN_0297 and PGN_0300 genes reduced the proteolytic activity of gingipains. The role of the PGN_0296 gene, consisting of an operon with the PGN_0297 and PGN_0300 genes, is unclear. Herein, we examined the effect of PGN_0296 gene deletion on the proteolytic activity. Although the proteolytic activity of the gingipains did not decrease in the culture supernatant of a PGN_0296 gene deletion mutant (ΔPGN_0296), the growth was delayed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2211-7539302020A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery2225ENKensukeUraguchiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenichiKozakuraDepartment of Otorhinolaryngology, Kochi Health Sciences CenterSatoshiOkaDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterTakayaHigakiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroMakiharaDepartment of Otorhinolaryngology, Head and Neck Surgery, Kagawa Rosai HospitalToshiImaiDepartment of Hematology and Blood Transfusion, Kochi Health Sciences CenterAkiraDoiDepartment of Otorhinolaryngology, Kochi Health Sciences CenterTsuyoshiOhtaDepartment of Neurosurgery, Kochi Health Sciences CenterShinKariyaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazunoriNishizakiDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesA 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2211-3355202020Gender differences in dietary behaviors among Japanese adolescents101203ENYuichiroOtsukaDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineYoshitakaKaneitaDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineOsamuItaniDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineMakiJikeDivision of Public Health, Department of Social Medicine, Nihon University School of MedicineYoneatsuOsakiDivision of Environmental and Preventive Medicine, Department of Social Medicine, Faculty of MedicineSusumuHiguchiNational Hospital Organization Kurihama Medical and Addiction CenterHideyukiKandaDepartment of Public Health, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, University Faculty of MedicineUnhealthy dietary behaviors in adolescence are an important public health problem. Gender differences in dietary behaviors have already appeared during adolescence. However, few studies have assessed a variety of adolescent dietary behaviors in Japan. We aimed to clarify gender differences in unhealthy dietary behaviors among Japanese adolescents. The participants consisted of 84,988 participants from seventh to 12th grades. Unhealthy dietary behaviors were defined according to the National Health and Nutrition Survey. Multivariable logistic regression was used to analyze a nationally representative sample of Japanese adolescents from the 2014 to 2015 Lifestyle Survey. The effective response rate was 51.4%. The prevalence of unhealthy dietary behaviors (skipping breakfast, snacking, eating out, skipping meals, eating alone at dinner, and subjectively poor diet quality) among boys and girls was 14.2% versus 12.4%, 19.6% versus 14.1%, 10.6% versus 7.0%, 7.9% versus 5.6%, 13.3% versus 12.1%, and 12.3% versus 15.8%, respectively. Compared with boys, girls were more negatively associated with skipping breakfast [OR = 0.76 (95% CI 0.73–0.79)], snacking [OR = 0.67 (95% CI 0.65–0.70)], eating out [OR = 0.62 (95% CI 0.59–0.66)], skipping meals [OR = 0.61 (95% CI 0.58–0.65)], and eating alone at dinner [OR = 0.79 (95% CI 0.76–0.83)]. However, girls were more positively associated with subjectively poor diet quality [OR = 1.19 (95% CI 1.14.1.24)]. The findings suggest that gender differences existed in dietary behaviors. Gender differences in dietary behaviors suggest opportunities for tailoring interventions related to dietary education in schools.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-6502212020A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure100284ENNobutoshiMorimotoDepartment of Neurology, Kagawa Central Prefectural HospitalMizukiMorimotoDepartment of Neurology, Kagawa Central Prefectural HospitalYoshiakiTakahashiDepartment of Neurology, Kagawa Central Prefectural HospitalMotonoriTakamiyaDepartment of Neurology, Kagawa Central Prefectural HospitalIchizoNishinoDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)KojiAbeDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University[Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071312020Extracorporeal membrane oxygenation in Stenotrophomonas maltophilia pneumonia during acute myeloid leukemia: A case report101224ENKenkiSaitoDepartment of Hematology/Oncology, Kurashiki Central HospitalToshiyukiAokageDepartment of Geriatric Emergency Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakayukiSatoDepartment of Hematology/Oncology, Kurashiki Central HospitalKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University HospitalFumiakiTokiokaDepartment of Respiratory Medicine, Kurashiki Central HospitalTakanaoOtakeDepartment of Anesthesiology, Kurashiki Central HospitalHiromasaIrieDepartment of Anesthesiology, Kurashiki Central HospitalYasunoriUedaDepartment of Hematology/Oncology, Kurashiki Central HospitalStenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, multidrug-resistant organism that both opportunistically infects the bloodstream and leads to pneumonia in immunosuppressed patients, including those with hematologic malignancies. In patients with severe respiratory failure, venovenous extracorporeal membrane oxygenation (VV ECMO) can stabilize the respiratory status. However, whether ECMO in patients with hematologic malignancies improves the clinical outcomes is still controversial because ECMO increases the risk of the exacerbation of sepsis and bleeding. We report a case of a 46-year-old man with Stenotrophomonas maltophilia hemorrhagic pneumonia acquired during consolidation chemotherapy for acute myeloid leukemia in whom VV ECMO lead to a good clinical outcome. The stabilization of his respiratory status achieved with VV ECMO allowed time for trimethoprim-sulfamethoxazole antibiotic therapy to improve the pneumonia. We suggest the background of patients, including comorbidities and general conditions, should be taken into account when considering the clinical indications of ECMO.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2214-4269252020Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials100643ENHitomiNishizawaFaculty of Health Sciences, Department of Medicine, Shinshu UniversityYoshihikoSatoDepartment of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, MatsumotoMasumiIshikawaCenter for Medical Genetics, Shinshu University HospitalYukoArakawaDepartment of Dentistry and Oral Surgery, Shinshu University School of MedicineMariIijimaDepartment of Clinical Nutrition, Shinshu University HospitalTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKyokoTakanoCenter for Medical Genetics, Shinshu University HospitalAtsushiWatanabeDivision of Clinical Genetics, Kanazawa University HospitalTomokiKoshoCenter for Medical Genetics, Shinshu University HospitalHypophosphatasia (HPP) is a rare disorder resulting from biallelic loss-of-function variants or monoallelic dominant negative variants in the ALPL gene. We herein describe the clinical outcome of a 32-year-old woman with childhood-onset HPP caused by compound heterozygous variants in ALPL. Her chief complaints were severe musculoskeletal pain, muscle weakness, and impaired daily activities necessitating assistance in housework and child-rearing in addition to a history of early tooth loss and mildly short stature. Asfotase alfa therapy produced a remarkable increase in muscle strength and daily activities and markedly reduced musculoskeletal pain. Drug efficacy was clearly demonstrated through multiple test batteries (muscle strength test using microFET®2, six-minute walking test, Stair Climb Test, rising-from-floor-time test, and number-of-steps test using Actigraph®) currently adopted as standardized evaluations in Duchenne muscular dystrophy clinical trials since no test batteries for HPP have been established to date. These tests may also be promising for the assessment of HPP.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2215-016172020Technique for single-step lymphocyte isolation from an endoscopic biopsy specimen for the diagnosis of gastrointestinal lymphoma101095ENMasayaIwamuroDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahideTakahashiDivision of Medical Support, Okayama University HospitalNatsukiWatanabeDivision of Medical Support, Okayama University HospitalSizumaOmoteDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKatsunoriMatsuedaDepartment of Gastrointestinal Oncology, Osaka International Cancer InstituteTakehiroTanakaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaisukeEnnishiDepartment of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTadashiYoshinoDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIn this paper, we introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment. For lymphocyte isolation, an endoscopically harvested specimen and 5 mL of normal saline solution were placed in a wire mesh strainer set in a porcelain bowl. To obtain the lymphocyte suspension, the solid specimen was crushed using the rubber portion of a plunger of a 10 mL injection syringe. Flow cytometry was performed using the lymphocyte suspension. For validating our methods, the one-step lymphocyte isolation technique was used to perform flow cytometry on samples from 23 patients with (n = 12) or without (n = 11) gastrointestinal lymphoma. Flow cytometry of light chain expression was performed in all patient samples (feasibility: 100%). Sensitivity was 83.3% (10/12) and specificity was 100% (11/11). In conclusion, lymphocytes isolated from a single endoscopic biopsy specimen using our simplified and quick procedure are suitable for flow cytometry. Considering that flow cytometry has an important advantage of providing the results on the examination day itself, the results of this study suggest that flow cytometric analysis using our single-step lymphocyte isolation technique can be potentially used to diagnose lymphoma in the gastrointestinal mucosa.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2451-830192020Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy102114ENHiroshiUenoDepartment of Medical Technology, Kawasaki University of Medical WelfareAtsumiShimadaDivision of Food and Nutrition, Nakamura Gakuen University Junior CollegeShunsukeSuemitsuDepartment of Psychiatry, Kawasaki Medical SchoolShinjiMurakamiDepartment of Psychiatry, Kawasaki Medical SchoolNaoyaKitamuraDepartment of Psychiatry, Kawasaki Medical SchoolKentaWaniDepartment of Psychiatry, Kawasaki Medical SchoolYuTakahashiDepartment of Psychiatry, Kawasaki Medical SchoolYosukeMatsumotoDepartment of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMotoiOkamotoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakeshiIshiharaDepartment of Psychiatry, Kawasaki Medical SchoolUnderstanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear.</br>
Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules.</br>
Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612772020Retropharyngeal hematoma presenting airway obstruction: A case report321324ENAtsuyoshiIidaDepartment of Emergency Medicine, Okayama Red Cross HospitalAyumiNishidaepartment of Neurosurgery, Okayama Red Cross HospitalSeijiYoshitomiDepartment of Breast and Endocrine Surgery, Okayama Red Cross HospitalTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIntroduction</br>
Blunt neck trauma patients can suffer from an airway emergency and are necessary to careful observation.</br>
Presentation of cas</br>e
A 79-year-old man under anticoagulation therapy presented to our hospital three hours after a fall. Shortly after arrival, he developed dyspnea. Oral intubation was attempted, but with no success; therefore, an emergency tracheotomy was performed. Contrast-enhanced computed tomography (CT) and subsequent angiography revealed active bleeding from a branch of the right ascending cervical artery. Subsequently, the right thyrocervical trunk, which is upstream from the ascending cervical artery, was embolized and hemostasis was achieved. He was discharged 52 days after the emergency admission.</br>
Discussion</br>
This is the first case report of an ascending cervical artery injury due to blunt trauma that resulted in an airway emergency. Contrast-enhanced CT and cervical angiography are useful for confirming the area of injury and size of the hematoma. Half of patients with respiratory distress accompanied by a cervical spine injury require definitive airway management within five hours of the injury and all by 24 h. Neck trauma can lead to fatal airway obstruction and careful monitoring is warranted to detect any signs of impeding respiratory obstruction.</br>
Conclusion</br>
All emergency physicians need to keep their airway management skills updated in order to perform reliably and rapidly in difficult and urgent situations.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3964622020A detection method for latent circadian rhythm sleep-wake disorder103080ENMakotoAkashiThe Research Institute for Time Studies, Yamaguchi UniversityReimiSogawaDepartment of Clinical Genetics and Genomic Medicine, Okayama University HospitalRitsukoMatsumuraThe Research Institute for Time Studies, Yamaguchi UniversityAtsuhiroNishidaThe Research Institute for Time Studies, Yamaguchi UniversityRinoNakamuraThe Research Institute for Time Studies, Yamaguchi UniversityIsao T.TokudaDepartment of Mechanical Engineering, Ritsumeikan UniversityKoichiNodeDepartment of Cardiovascular Medicine, Saga UniversityBackground</br>
Individuals with typical circadian rhythm sleep-wake disorders (CRSWDs) have a habitual sleep timing that is desynchronized from social time schedules. However, it is possible to willfully force synchronisation against circadian-driven sleepiness, which causes other sleep problems. This pathology is distinguishable from typical CRSWDs and is referred to here as latent CRSWD (LCRSWD). Conventional diagnostic methods for typical CRSWDs are insufficient for detecting LCRSWD because sufferers have an apparently normal habitual sleep timing.</br>
Methods</br>
We first evaluated the reliability of circadian phase estimation based on clock gene expression using hair follicles collected at three time points without sleep interruption. Next, to identify detection criteria for LCRSWD, we compared circadian and sleep parameters according to estimated circadian phases, at the group and individual level, between subjects with low and high Pittsburgh Sleep Quality Index (PSQI) scores. To validate the reliability of identified detection criteria, we investigated whether the same subjects could be reproducibly identified at a later date and whether circadian amelioration resulted in sleep improvement.</br>
Findings</br>
We successfully validated the reliability of circadian phase estimation at three time points and identified potential detection criteria for individuals with LCRSWD attributed to delayed circadian-driven sleepiness. In particular, a criterion based on the interval between the times of the estimated circadian phase of clock gene expression and getting out of bed on work or school days was promising. We also successfully confirmed the reproducibility of candidate screening and sleep improvement by circadian amelioration, supporting the reliability of the detection criteria.</br>
Interpretation</br>
Although several limitations remain, our present study demonstrates a promising prototype of a detection method for LCRSWD attributed to delayed circadian-driven sleepiness. More extensive trials are needed to further validate this method.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0197-01861412020Scn1a and Cacna1a mutations mutually alter their original phenotypes in rats104859ENIoriOhmoriGraduate School of Education, Okayama UniversityKiyokaKobayashiDepartment of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamoruOuchidaDepartment of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThis study aimed to examine the effects of Cacna1a mutation on the phenotype of Scn1a-associated epilepsy in rats. We used rats with an N1417H missense mutation in the Scn1a gene and others with an M251K mutation in the Cacna1a gene. Scn1a/Cacna1a double mutant rats were generated by mating both Scn1a and Cacna1a mutants. We investigated general health and the epileptic phenotype in all these genotypes. The onset threshold of hyperthermia-induced seizures was examined at 5 weeks and spontaneous seizures were monitored using video-EEG recordings from 6 to 12 weeks of age. Scn1a/Cacna1a double mutants showed significantly reduced threshold for hyperthermia-sensitive seizures onset compared with the Scn1a mutants and had absence seizures having 6–7 c/s spike-wave bursts with changes in the spike-wave pattern, whereas Cacna1a mutants had regular 6–7 c/s spike-wave bursts. In Scn1a/Cacna1a double mutants, 6–7 c/s spike-wave bursts were accompanied with eyelid myoclonia and continuously shifting generalized clonic seizures, which were not observed in either Scn1a or Cacna1a mutants. Although a curvature of the spine was observed in rats of all these genotypes, the degree of curvature was more pronounced in Scn1a/Cacna1a double mutants, followed by Cacna1a and Scn1a mutants. Our results indicate that Cacna1a and Scn1a mutations mutually alter their original phenotypes in rats. The phenotype of absence seizures with eyelid myoclonia, generalized clonic seizures, and of spine curvature in the Scn1a/Cacna1a double mutants were similar to that observed in patients with Dravet syndrome.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0887-89941132020Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate3341ENTomoyukiAkiyamaDepartment of Child Neurology, Okayama University HospitalYukiHyodoDepartment of Child Neurology, Okayama University HospitalKoseiHasegawaDepartment of Pediatrics, Okayama University HospitalTaikanOboshiDepartment of Pediatric Neurology, Osaka Women’s and Children’s HospitalKatsumiImaiDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersNaokoIshiharaDepartment of Pediatrics, Fujita Health University School of MedicineYuriDowaDepartment of Neurology, Gunma Children’s Medical CenterTakayoshiKoikeDepartment of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological DisordersToshiyukiYamamotoInstitute of Clinical Genomics, Tokyo Women’s Medical UniversityJunShibasakiDepartment of Neonatology, Kanagawa Children’s Medical CenterHirokoShimboClinical Institute, Kanagawa Children’s Medical CenterTetsuhiroFukuyamaDepartment of Pediatrics, Shinshu UniversityKyokoTakanoCenter for Medical Genetics, Shinshu University HospitalHiroshiShirakuDepartment of Pediatrics, JA Toride Medical CenterSaokoTakeshitaDepartment of Pediatrics, Yokohama City University Medical CenterTohruOkanishiDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General HospitalShimpeiBabaDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General HospitalMasayaKubotaDivision of Neurology, National Center for Child Health and DevelopmentShin-ichiroHamanoDivision of Neurology, Saitama Children’s Medical CenterKatsuhiroKobayashiDepartment of Child Neurology, Okayama University HospitalBackground</br>
We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid.</br>
Methods</br>
Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations.</br>
Results</br>
We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain.</br>
Conclusions</br>
Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0013-46863632020Sophisticated rGO synthesis and pre-lithiation unlocking full-cell lithium-ion battery high-rate performances137257ENBenoît Denis Louis CampéonGraduate School of Natural Science and Technology, Okayama UniversityYumiYoshikawaGraduate School of Natural Science and Technology, Okayama UniversityTakashiTeranishiGraduate School of Natural Science and Technology, Okayama UniversityYutaNishinaGraduate School of Natural Science and Technology, Okayama UniversityFor the application to portable devices and storage of renewable energies, high-performance lithium-ion batteries are in great demand. To this end, the development of high-performance electrode materials has been actively investigated. However, even if new materials exhibit high performance in a simple evaluation, namely half-cell tests, it is often impossible to obtain satisfactory performance with an actual battery (full cell). In this study, the structure of graphene analogs is modified in various ways to change crystallinity, disorder, oxygen content, electrical conductivity, and specific surface area. These graphene analogs are evaluated as negative electrodes for lithium-ion batteries, and we found reduced graphene oxide prepared by combination of chemical reduction and thermal treatment was the optimum. In addition, a full cell is fabricated by combining it with LiCoO2 modified with BaTiO3, which is applicable to high-speed charge–discharge cathode material developed in our previous research. In general, pre-lithiation is performed for the anode when assembling full cells. In this study, we optimized a "direct pre-lithiation" method in which the electrode and lithium foil were in direct contact before assembling a full cell, and created a lithium-ion battery with an output of 293 Wh kg−1 at 8,658 W kg−1.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0278-4165602020Isotopic proveniencing at Classic Copan and in the southern periphery of the Maya Area: A new perspective on multi-ethnic society101228ENShintaroSuzukiGraduate School of Humanities and Social Sciences, Okayama UniversitySeiichiNakamuraCenter for Cultural Resource Studies, Institute of Human and Social Sciences, Kanazawa UniversityT. DouglasPriceLaboratory for Archaeological Chemistry, University of WisconsinStrontium, oxygen, and carbon isotopes were measured in human tooth enamel from 66 burials in 9L-22 and 9L-23 residential groups at the Classic Maya site of Copan in western Honduras. These results are discussed in relation to earlier studies at Copan and baseline measurements from the surrounding region and the Maya area in general. Nearly 50% of the individuals are identified as non-local based on combinations of strontium, oxygen, and carbon isotope ratios. They came from a variety of places in the Maya area. This migratory pattern at the 9L-22 & 9L-23 residential complex from the Early to Late Classic (ca. 400–800 CE) is compared with 10J-45 sector from the mainly Early Classic occupation (ca. 400–650 CE) and an interesting change is noted. The social privileges observed among the Early Classic immigrants from the north Maya Lowlands were apparently revoked in the Late Classic. New immigrants, probably from the “non-Maya” regions of Western/Central Honduras, appear to have gained those social privileges. High-status Honduran individuals in the urban core suggests a strategy by the Copan dynasty in the Late Classic that incorporated the emerging “non-Maya” elites from Western/Central Honduras.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1590-86585172019Adenomyomatosis hyperplasia arising in the bile duct1060ENKazuyukiMatsumotoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironariKatoDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiNishidaDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiOkadaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1010-60304052021Exploring reaction pathways for the structural rearrangements of the Mn cluster induced by water binding in the S3 state of the oxygen evolving complex of photosystem II112905ENHiroshiIsobeResearch Institute for Interdisciplinary Science, Okayama UniversityMitsuoShojiCenter for Computational Science, University of TsukubaTakayoshiSuzukiResearch Institute for Interdisciplinary Science, Okayama UniversityJian-RenShenResearch Institute for Interdisciplinary Science, Okayama UniversityKizashiYamaguchiInstitute for NanoScience Design, Osaka UniversityPhotosynthetic oxidation of water to dioxygen is catalyzed by the Mn4CaO5 cluster in the protein-cofactor complex photosystem II. The light-driven catalytic cycle consists of four observable intermediates (S0, S1, S2, and S3) and one transient S4 state. Recently, using X-ray free-electron laser crystallography, two experimental groups independently observed incorporation of one additional oxygen into the cluster during the S2 to S3 transition, which is likely to represent a substrate. The present study implicates two competing reaction routes encountered during the structural rearrangement of the catalyst induced by the water binding and immediately preceding the formation of final stable forms in the S3 state. This mutually exclusive competition involves concerted versus stepwise conformational changes between two isomers, called open and closed cubane structures, which have different consequences on the immediate product in the S3 state. The concerted pathway involves a one-step conversion between two isomeric hydroxo forms without changes to the metal oxidation and total spin (Stotal = 3) states. Alternatively, in the stepwise process, the bound waters are oxidized and transformed into an oxyl–oxo form in a higher spin (Stotal = 6) state. Here, density functional calculations are used to characterize all relevant intermediates and transition structures and demonstrate that the stepwise pathway to the substrate activation is substantially favored over the concerted one, as evidenced by comparison of the activation barriers (11.1 and 20.9 kcal mol−1, respectively). Only after formation of the oxyl–oxo precursor can the hydroxo species be generated; this occurs with a slow kinetics and an activation barrier of 17.8 kcal mol−1. The overall thermodynamic driving force is likely to be controlled by the movements of two glutamate ligands, D1-Glu189 and CP43-Glu354, in the active site and ranges from very weak (+0.4 kcal mol−1) to very strong (–23.5 kcal mol−1).No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1566-07022282020Orexin A and B in the rat superior salivatory nucleus102712ENTadasuSatoDivision of Oral and Craniofacial Anatomy, Tohoku University Graduate School of DentistryTakehiroYajimaDivision of Oral and Craniofacial Anatomy, Tohoku University Graduate School of DentistryMasakoFujitaDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesMotoiKobashiDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesHiroyukiIchikawaDivision of Oral and Craniofacial Anatomy, Tohoku University Graduate School of DentistryRyusukeYoshidaDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesYoshihiroMitohDepartment of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical SciencesOrexin (OX), which regulates sleep and wakefulness and feeding behaviors has 2 isoforms, orexin-A and -B (OXA and OXB). In this study, the distribution of OXA and OXB was examined in the rat superior salivatory nucleus (SSN) using retrograde tracing and immunohistochemical and methods. OXA- and OXB-immunoreactive (-ir) nerve fibers were seen throughout the SSN. These nerve fibers surrounded SSN neurons retrogradely labeled with Fast blue (FB) from the corda-lingual nerve. FB-positive neurons had pericellular OXA- (47.5%) and OXB-ir (49.0%) nerve fibers. Immunohistochemistry for OX receptors also demonstrated the presence of OX1R and OX2R in FB-positive SSN neurons. The majority of FB-positive SSN neurons contained OX1R- (69.7%) or OX2R-immunoreactivity (57.8%). These neurons had small and medium-sized cell bodies. In addition, half of FB-positive SSN neurons which were immunoreactive for OX1R (47.0%) and OX2R (52.2%) had pericellular OXA- and OXB-ir nerve fibers, respectively. Co-expression of OX1R- and OX2R was common in FB-positive SSN neurons. The present study suggests a possibility that OXs regulate the activity of SSN neurons through OX receptors.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-17022442018A neo-virus lifestyle exhibited by a (+)ssRNA virus hosted in an unrelated dsRNA virus: Taxonomic and evolutionary considerations7583ENSakaeHisanoInstitute of Plant Science and Resources (IPSR), Okayama UniversityRuiZhangInstitute of Plant Science and Resources (IPSR), Okayama UniversityMd. IqbalFarukInstitute of Plant Science and Resources (IPSR), Okayama UniversityHidekiKondoInstitute of Plant Science and Resources (IPSR), Okayama UniversityNobuhiroSuzukiInstitute of Plant Science and Resources (IPSR), Okayama UniversityRecent studies illustrate that fungi as virus hosts provides a unique platform for hunting viruses and exploring virus/virus and virus/host interactions. Such studies have revealed a number of as-yet-unreported viruses and virus/virus interactions. Among them is a unique intimate relationship between a (+)ssRNA virus, yado-kari virus (YkV1) and an unrelated dsRNA virus, yado-nushi virus (YnV1). YkV1 dsRNA, a replicated form of YkV1, and RNA-dependent RNA polymerase, are trans-encapsidated by the capsid protein of YnV1. While YnV1 can complete its replication cycle, YkV1 relies on YnV1 for its viability. We previously proposed a model in which YkV1 diverts YnV1 capsids as the replication sites. YkV1 is neither satellite virus nor satellite RNA, because YkV1 appears to encode functional RdRp and enhances YnV1 accumulation. This represents a unique mutualistic virus/virus interplay and similar relations in other virus/host fungus systems are detectable. We propose to establish the family Yadokariviridae that accommodates YkV1 and recently discovered viruses phylogenetically related to YkV1. This article overviews what is known and unknown about the YkV1/YnV1 interactions. Also discussed are the YnV1 Phytoreo_S7 and YkV1 2A-like domains that may have been captured via horizontal transfer during the course of evolution and are conserved across extant diverse RNA viruses. Lastly, evolutionary scenarios are envisioned for YkV1 and YnV1.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0141-6359652020Thermal influence on surface layer of carbon fiber reinforced plastic (CFRP) in grinding5363ENHiroyukiKodamaOkayama UniversityShingoOkazakiOkayama UniversityYifanJiangOkayama UniversityHiroyukiYodenIndustrial Technology Research Institute of Okayama Prefectural GovernmentKazuhitoOhashiOkayama UniversityIn this study, we investigated thermal influence on surface layer of CFRP in grinding with heat conduction analysis using grinding temperature at wheel contact area on dry and wet condition. Moreover, the thermal affected layer was analyzed through an experiment to examine the temperature of glass transition and thermal decomposition of the matrix resin that composes the CFRP used in this study. The influence of thermal effect on grinding of CFRP was verified based on observation of ground surface finish after grinding using SEM and the measurement of surface roughness. From the measurement result of DSC (Differential Scanning Calorimetry)，TG-DTA (Thermogravimetry-Differential Thermal Analysis), It was found that the thermal affected layer of CFRP includes a layer in which the matrix resin is changed in quality by exceeding the glass transition temperature and a layer in which the matrix resin is thermally decomposed by exceeding the thermal decomposition temperature. In addition, it was found that the surface roughness was significantly reduced if the thermal affected layer with thermal decomposition was generated. In each grinding atmosphere, it tended to increase of grinding temperature at wheel contact area with increasing in the setting depth of cut. In the case of dry grinding, grinding temperature at wheel contact area increased up to t thermal decomposition temperature of the matrix resin. However, in the case of the wet grinding, grinding temperature at wheel contact area did not increase until thermally decomposition temperature. From the result of simulation about thermal affected layer, influence of grinding heat increased with increasing in the setting depth of cut. Ultimately, the thermal affected layer with thermal decomposition was generated in dry grinding. Moreover, from the results of SEM observation, it was confirmed that the surface finish properties deteriorated significantly due to thermal decomposition of the matrix resin in the case of Δ = 400 μm in the setting depth of cut at fiber angle θ = 0°. On the other hand, it was confirmed that the micro damage of carbon fiber was occurred in wet grinding at each setting depth of cut.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0048-969774112020Long-term exposure to nitrogen dioxide and natural-cause and cause-specific mortality in Japan140465ENTakashiYorifujiDepartment of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySaoriKashimaEnvironmental Health Sciences Laboratory, Graduate School for International Development and Cooperation, Hiroshima UniversityBackground</br>
Long-term exposure to air pollution is linked with increased risk of adverse health outcomes, but the evidence for the association between nitrogen dioxide (NO2) and mortality is weak because of the inadequate adjustment of potential confounders and limited spatial resolution of the exposure assessment. Moreover, there are concerns about the independent effects of NO2. Therefore, we examined the association between NO2 long-term exposure and all-cause and cause-specific mortality.</br>
Methods</br>
We included participants who were enrolled in health checkups in Okayama City, Japan, in 2006 or 2007 and were followed until 2016. We used a land-use regression model to estimate the average NO2 concentrations from 2006 to 2007 and allocated them to the participants. We estimated hazard ratios (HRs) for a 10-μg/m3 increase in NO2 levels for all-cause or cause-specific mortality using Cox proportional hazard models.</br>
Results</br>
After excluding the participants who were assigned with outlier exposures, a total of 73,970 participants were included in the analyses. NO2 exposure was associated with increased risk of mortality and the HRs and their confidence intervals were 1.06 (95% CI: 1.02, 1.11) for all-cause, 1.02 (0.96, 1.09) for cardiopulmonary, and 1.36 (1.14, 1.63) for lung cancer mortality. However, the elevated risks became equivocal after the adjustment for fine particulate matter except lung cancer.</br>
Conclusion</br>
Long-term exposure to NO2 was associated with increased risk of all-cause, cardiopulmonary, and lung cancer mortality. The elevated risk for lung cancer was still observable even after adjustment for fine particulate matter.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1873-5061462020Adult kidney stem/progenitor cells contribute to regeneration through the secretion of trophic factors101865ENKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYizhenSangDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesAdult kidney stem cells are known to have important roles in renal regeneration after acute kidney injury. Although trophic factors from tissue stem cells have been reported to promote the regeneration of other organs, there is limited number of evidence of this phenomenon in the kidneys. Here, we explored the effects of secreted factors from kidney stem cells. We intraperitoneally administered culture supernatant obtained from adult rat kidney stem/progenitor cells into rat kidney ischemia/reperfusion injury models, and the treatment significantly ameliorated renal tubulointerstitial injury, suppressed tubular cell apoptosis, diminished inflammation and promoted the proliferation of both residual renal cells and immature cells. In vitro, treatment with culture supernatant from kidney stem cells significantly promoted cell proliferation and suppressed cisplatin-induced cell apoptosis in both normal rat kidney cells and kidney stem cells. In addition, treatment with culture supernatant increased the expression of nestin in normal rat kidney cells, suggesting the dedifferentiation of tubular cells into stem-like cells. Analysis of the culture supernatant revealed that it contained a variety of growth factors. Taken together, the results suggest that these factors together lead to renal regeneration. In conclusion, adult kidney stem cells contribute to renal regeneration indirectly through the secretion of regenerative factors.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X26102020Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome10951099ENKosukeOkaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMaiYamaneDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuyaYokotaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMihoYasudaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKouHasegawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakumiFujimoriMicrobiology Division, Clinical Laboratory, Okayama University HospitalKojiIioMicrobiology Division, Clinical Laboratory, Okayama University HospitalHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1341-321X26102020Antibiotic literacy among Japanese medical students11071109ENHideharuHagiyaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideoInoCenter for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiTokumasuDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokoOgawaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMiyoshiDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanakoOchiCenter for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAntimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24680249592020Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells15761580ENNatsumiMatsuoka-UchiyamaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiTsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhikoFukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiKitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHaruhito A.UchidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiSugiyamaDepartment of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaokiTakahashiDepartment of Nephrology, Faculty of Medical Science, University of FukuiMasayukiIwanoDepartment of Nephrology, Faculty of Medical Science, University of FukuiJunWadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666250732020Bilateral segmental lung transplantation for children: Transplantation using split adult living-donor lower lobe311314ENTakahiroOtoTransplant Center, Okayama University HospitalYukikoHikasaAnesthesiology and Resuscitology, Okayama University HospitalAkikazuHagiyamaPhysical Medicine and Rehabilitation, Okayama University HospitalMotomuKobayashiAnesthesiology and Resuscitology, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24058440662020Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water linese04132ENKeisukeOkuboDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiItoCenter for Innovative Clinical Medicine, Okayama University HospitalKentaroOkamotoDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIchiroYamamotoDental Department Marketing Division, TAKARA BELMONT CorporationHajimeMizutaniResearch and Development Department, TAKARA BELMONT CorporationYusukeKawataDepartment of Periodontics and Endodontics, Okayama University HospitalYasuyoshiShiotaDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroItoDepartment of Periodontics and Endodontics, Okayama University HospitalShinNakamuraDepartment of Periodontics and Endodontics, Okayama University HospitalMasakoTaiDepartment of Periodontics and Endodontics, Okayama University HospitalTadashiYamamotoDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceThe prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination.</br>
Objectives</br>
To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL.</br>
Methods</br>
The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium.</br>
Results</br>
The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods.</br>
Conclusions</br>
The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440662020Rapid and specific detection of oxidized LDL/β2GPI complexes via facile lateral flow immunoassaye04114ENXian WenTanDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiakiTakenakaCollaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironoriTakekawaFaculty of Medicine, Okayama UniversityEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciencesβ2-Glycoprotein I (β2GPI) forms indissociable complex with oxidized LDL (oxLDL) into proatherogenic oxLDL/β2GPI complex through a specific ligand known as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1). Recent discoveries have demonstrated the atherogenicity of these complexes in patients of both systemic and non-systemic autoimmune diseases. Hence, serological level of oxLDL/β2GPI complexes may represent one crucial clinical parameter for disease prognosis of atherosclerosis-related diseases. Herein, we established a simple, specific and rapid gold nanoparticle (GNP) based lateral flow immunoassay (LFIA) to quantify oxLDL/β2GPI complexes from test samples. Specificities of hybridoma cell-derived monoclonal antibodies against antigen, optimal conditions for conjugation of antibody with GNP, and sensitivity of oxLDL/β2GPI LFIA in comparison to an ELISA-based detection method were assessed accordingly. The established oxLDL/β2GPI LFIA was capable of detecting oxLDL/β2GPI specifically without interference from autoantibodies and solitary components of oxLDL/β2GPI present in test samples. A significant correlation (R2 > 0.8) was also obtained with the oxLDL/β2GPI LFIA when compared to the ELISA-based detection. On the whole, the oxLDL/β2GPI LFIA remains advantageous over the oxLDL/β2GPI ELISA. The unnecessary washing step, short developmental and analytical time support facile and rapid detection of oxLDL/β2GPI as opposed to the laborious ELISA system.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0005-2728186172020Spectral tuning of light-harvesting complex II in the siphonous alga Bryopsis corticulans and its effect on energy transfer dynamics148191ENParveenAkhtarBiological Research CentrePaweł J.Nowakowskiivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological UniversityWendaWangPhotosynthesis Research Centre, Chinese Academy of SciencesThanh NhutDoDivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological UniversitySonghaoZhaoPhotosynthesis Research Centre, Chinese Academy of SciencesGiulianoSiligardiDiamond Light Source Ltd., Harwell Science and Innovation CampusGyőzőGarabBiological Research CentreJian-RenShenResearch Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama UniversityHowe-SiangTanDivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological UniversityPetar H.LambrevBiological Research CentreLight-harvesting complex II (LHCII) from the marine green macroalga Bryopsis corticulans is spectroscopically characterized to understand the structural and functional changes resulting from adaptation to intertidal environment. LHCII is homologous to its counterpart in land plants but has a different carotenoid and chlorophyll (Chl) composition. This is reflected in the steady-state absorption, fluorescence, linear dichroism, circular dichroism and anisotropic circular dichroism spectra. Time-resolved fluorescence and two-dimensional electronic spectroscopy were used to investigate the consequences of this adaptive change in the pigment composition on the excited-state dynamics. The complex contains additional Chl b spectral forms – absorbing at around 650 nm and 658 nm – and lacks the red-most Chl a forms compared with higher-plant LHCII. Similar to plant LHCII, energy transfer between Chls occurs on timescales from under hundred fs (mainly from Chl b to Chl a) to several picoseconds (mainly between Chl a pools). However, the presence of long-lived, weakly coupled Chl b and Chl a states leads to slower exciton equilibration in LHCII from B. corticulans. The finding demonstrates a trade-off between the enhanced absorption of blue-green light and the excitation migration time. However, the adaptive change does not result in a significant drop in the overall photochemical efficiency of Photosystem II. These results show that LHCII is a robust adaptable system whose spectral properties can be tuned to the environment for optimal light harvesting.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama094926582632020High body mass index is a risk factor for unfavorable clinical outcomes after medial meniscus posterior root repair in well-aligned knees430434ENXimingZhangDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakaakiHiranakaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuyaKodamaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHaoweiXueDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikiOkazakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University HospitalBackgroundSevere chondral lesions and varus knee alignment are associated with poor outcomes following transtibial pullout repair for medial meniscus posterior root tears and meniscus tear is strongly associated with body mass index. The prognostic factors in well-aligned knees (femorotibial angle < 180°) with mild chondral lesions are unknown. Therefore, we investigated the prognostic factors in these patients. We hypothesized that high body mass index would lead to poor clinical outcomes following pullout repair of medial meniscus posterior root tears. <br>
MethodsWe retrospectively reviewed the files of 28 patients who had undergone pullout repair of medial meniscus posterior root tears between October 2016 and December 2017. We recorded the baseline characteristics (age, gender, height, weight, and body mass index) and the time between injury and surgery. We recorded the International Knee Documentation Committee scores, Knee injury and Osteoarthritis Outcome Scores, and pain visual analog scale scores. Using magnetic resonance imaging preoperatively and 1 year after surgery, we measured the medial meniscus body width and absolute and relative medial meniscus extrusion. Pearson correlation and multivariate linear regression analyses were used to assess potential associations between these factors and clinical outcomes. <br>
ResultsAge positively correlated (coefficient = 0.49, P < 0.01) and body mass index negatively correlated with the postoperative International Knee Documentation Committee score (coefficient = −0.64, P < 0.01). In multivariate linear regression analysis, body mass index was a significant factor leading to poor postoperative International Knee Documentation Committee score (R2 = 0.29, P < 0.05). <br>
ConclusionsBody mass index > 30 kg/m(2) is a risk factor for unfavorable clinical outcomes following pullout repair of medial meniscus posterior root tears in well-aligned knees. Level of evidenceIII, Comparative retrospective study.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-16053252020Isolation and identification of the antimicrobial substance included in tempeh using Rhizopus stolonifer NBRC 30816 for fermentation108645ENMasahiroItoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiItoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHideyukiAokiIkeda Food Research Co., Ltd.KoshiNishiokaIkeda Food Research Co., Ltd.TsugumiShiokawaDivision of Instrumental Analysis, Department of Instrumental Analysis and Cryogenics, Advanced Science Research Center, Okayama UniversityHirokoTadaDivision of Instrumental Analysis, Department of Instrumental Analysis and Cryogenics, Advanced Science Research Center, Okayama UniversityYukiTakeuchiDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityNobuyukiTakeyasuDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTadashiYamamotoDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShogoTakashibaDepartment of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn this study, we focus on the antimicrobial properties of tempeh, a soybean fermented food, against oral bacteria.</br>
Tempeh showed antimicrobial activity against dental caries pathogenic bacterium Streptococcus mutans at a final concentration of 1 mg/mL. An antimicrobial substance contained in tempeh was present in the 100 kDa or greater fraction generated by ultrafiltration, but it was found not to be proteinaceous by native-PAGE, SDS-PAGE and protein degradation tests. Next, when the fraction was purified with an ODS column, the 80% and 100% methanol eluates showed antimicrobial activity against S. mutans. The 100% methanol eluate was further subjected to a 2nd column purification, and isolation of the target was confirmed by HPLC. When the isolated material was analyzed by ESI-MS, the m/z was 279.234. Further analysis by Raman spectroscopy revealed a peak similar to linoleic acid. This substance also possessed antimicrobial properties equivalent to linoleic acid.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama24055808222020Neuroplastinβ-mediated upregulation of solute carrier family 22 member 18 antisense (SLC22A18AS) plays a crucial role in the epithelial-mesenchymal transition, leading to lung cancer cells' enhanced motility100768ENKarolinaBajkowskaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesI. WayanSumardikaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYouyiChenDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-ichiYamamotoDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiMurataDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNi LuhGede Yoni KomalasariDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFanJiangDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolI. MadeWinarsa RumaUniversity of SurreyCarlos IchiroKasano-CamonesFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOur recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified: tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. In vitro, the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression in vivo. The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2049-0801582020Continuing surgical education of non-technical skills177186ENMasaomiYamaneDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeiichiroSugimotoDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEtsujiSuzukiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeijuAokageDepartment of Thoracic Surgery, National Cancer Center Hospital EastMikioOkazakiDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesJunichiSohDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of MedicineMakioHayamaDepartment of Thoracic Surgery, Japanese Red Cross Okayama HospitalYujiHiramiDepartment of General Thoracic Surgery, National Hospital Organization Okayama Medical CenterTakashiYorifujiDepartment of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinichiToyookaDepartments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground</br>
The non-technical skills for surgeons (NOTSS) system was developed as a tool to assess surgical skills for patient safety during surgery. This study aimed to develop a NOTSS-based training system for surgical trainees to acquire non-technical skills using a chest surgery scenario in a wet lab.</br>
Materials and methods</br>
Trainees were categorized into three subgroups according to the years of experience as follows: Level A: 6 years or more; Level B: 3–5 years; and Level C: 1–2 years. Three stages of surgical procedure were designed: 1. chest wall resection and right upper lobe lobectomy, 2. right middle lobe sleeve lobectomy, and 3. right lower lobe lobectomy. One instructor was assigned to each operation table, who evaluated each participant's NOTSS scores consisting of 16 elements.</br>
Results</br>
When comparing average NOTSS score of all the three procedures, significant differences were observed between Level A, B, and C trainees. As an example of varying elements by procedure, Level A trainees demonstrated differences in Situation Awareness, and a significant difference was observed in Level C trainees regarding the elements of Decision Making. On the contrary, no significant difference was observed among Level B trainees. In the comparison between first-time and experienced participants, a significant improvement was observed in some elements in Level B and C trainees.</br>
Conclusion</br>
This study highlights the usefulness and feasibility of the NOTSS scoring system for surgeons with different experiences and the effectiveness of providing feedback to trainees during intraoperative handoffs in a wet lab.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama134900796232020Regulation of cellular communication network factor 2 (CCN2) in breast cancer cells via the cell-type dependent interplay between CCN2 and glycolysis280288ENShoAkashi Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiNishidaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomomiMizukawaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazumiKawataDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasaharuTakigawaDepartment of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiIida Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKubotaDepartment of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectives: Anti-osteoclastic treatments for breast cancer occasionally cause medication-related osteonecrosis of the jaw. Moreover, elevated glycolytic activity, which is known as the Warburg effect, is usually observed in these breast cancer cells. Previously, we found that cellular communication network factor 2 (CCN2) production and glycolysis enhanced each other in chondrocytes. Here, we evaluated the interplay between CCN2 and glycolysis in breast cancer cells, as we suspected a possible involvement of CCN2 in the Warburg effect in highly invasive breast cancer cells. <br/>
Methods: Two human breast cancer cell lines with a distinct phenotype were used. Glycolysis was inhibited by using 2 distinct compounds, and gene silencing was performed using siRNA. Glycolysis and the expression of relevant genes were monitored via colorimetric assays and quantitative RT-PCR, respectively. <br/>
Results: Although CCN2 expression was almost completely silenced when treating invasive breast cancer cells with a siRNA cocktail against CCN2, glycolytic activity was not affected. Notably, the expression of glycolytic enzyme genes, which was repressed by CCN2 deficiency in chondrocytes, tended to increase upon CCN2 silencing in breast cancer cells. Inhibition of glycolysis, which resulted in the repression of CCN2 expression in chondrocytic cells, did not alter or strongly enhanced CCN2 expression in the invasive and non-invasive breast cancer cells, respectively. <br/>
Conclusions: High CCN2 expression levels play a critical role in the invasion and metastasis of breast cancer. Thus, a collapse in the intrinsic repressive machinery of CCN2 due to glycolysis may induce the acquisition of an invasive phenotype in breast cancer cells. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0032-38612022020Preparation of solution-grown lozenge-shaped poly(p-phenylene terephthalamide) single crystals and their structural stabilization by heat treatment122672ENTetsuyaUchidaGraduate School of Natural Science and Technology, Okayama UniversityYutaroHaraGraduate School of Natural Science and Technology, Okayama UniversityTomoyasuTakakiGraduate School of Natural Science and Technology, Okayama UniversityIn this study, the preparation of poly (p-phenylene terephthalamide) (PPTA) single crystals was examined using crystallization from dilute solutions in concentrated sulfuric acid. Lozenge-shaped PPTA single crystals were successfully prepared using a self-seeding method with a low degree of supercooling, and they consisted of modification I crystals. The a-axis direction of the crystal corresponded to the long diagonal direction of the rhombus, the b-axis direction with the short diagonal direction, and the PPTA molecular chain direction (the c-axis direction) with the crystal's thickness direction. In addition, the PPTA single crystals had a (110) growth plane, where the thickness of each single crystal was approximately equal to the molecular chain length of the PPTA. Upon heat treatment of the PPTA single crystals, the symmetry changed from P1a1 to the more stable P11n. In addition, the heat treatment caused a difference in the density of each symmetric crystal, resulting in crack formation along the b-axis direction, which is the hydrogen-bonding direction. However, the heat treatment did not change the thickness of the PPTA single crystals. Conversely, the isothermal crystallization of the PPTA caused progression in the crystallization only under a high degree of supercooling, thus yielding plate-like PPTA crystals that consisted of modification II crystals. In these plate-like PPTA crystals, the length corresponded to the crystal a-axis direction, and the electron diffraction pattern was broad. Furthermore, the equilibrium dissolution temperature of the PPTA single crystals was discussed.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0003497511212020Anatomical Risk Factors for Reintervention after Arterial Switch Operation for Taussig–Bing Anomaly163169ENYasuyukiKobayashiCardiovascular Surgery, Okayama University HospitalYasuhiroKotaniCardiovascular Surgery, Okayama University HospitalYosukeKurokoCardiovascular Surgery, Okayama University HospitalAtsushiTateishiCardiovascular Surgery, Okayama University HospitalShunjiSanoPediatric Cardiothoracic Surgery, University of California, San FranciscoShingoKasaharaCardiovascular Surgery, Okayama University HospitalBackground: This study aimed to determine the factors related to reintervention, especially for pulmonary artery stenosis (PS), in patients with Taussig–Bing anomaly (TBA) after arterial switch operation (ASO).<br>
Methods:This retrospective study included 34 patients with TBA who underwent ASO between 1993 and 2018. Preoperative anatomical and physiological differences and long-term outcomes were determined using a case-matched control with transposition of the great arteries (TGA) with ventricular septal defect (VSD) and TBA with an anterior and rightward aorta. <br>
Results: The median age and body weight at ASO were 43 (16–102) days and 3.6 (2.8–3.8) kg, respectively. Aortic arch obstruction and coronary anomalies were present in 64% and 41% patients, respectively. The hospital mortality rate was 11%, including one cardiac death, and late mortality rate was 2.9%. Furthermore, 41% patients underwent 26 reinterventions for PS. Patients undergoing PS-related reintervention had a significantly larger native pulmonary artery: aortic annulus size ratio than those not receiving reintervention (1.69 vs. 1.41, P = 0.02). This ratio was the only predictor of PS-related reintervention; it was significantly higher in the TBA group than in the TGA/VSD group. PS-related reintervention was required more in the TBA group than in the TGA/VSD group. <br>
Conclusions: Regardless of complex coronary anatomy and associated anomalies, early and late survival were acceptable. Postoperative PS was strongly associated with having a larger native pulmonary valve, suggesting that an optimal surgical reconstruction was required for achieving an appropriate aortopulmonary anatomical relationship during ASO. (243 words)No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0006-291X53132020High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4422430ENYumiSakamotoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTatsuoOkuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceToshiyukiYonedaDepartment of Cellular and Molecular Biochemistry, Osaka University Graduate School of DentistryShojiRyumonDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTomoyaNakamuraDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHotakaKawaiDepartment of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukiKunisadaDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSoichiroIbaragiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasanoriMasuiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKishoOnoDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKyoichiObataDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTsuyoshiShimoDivision of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of HokkaidoAkiraSasakiDepartment of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceBone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0960-7404352020Low-grade soft-tissue sarcomas: What is an adequate margin for local disease control?303308ENTomohiroFujiwaraDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoichiKaneuchiOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustYusukeTsudaOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustJonathanStevensonOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustMichaelParryOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustLeeJeysOncology Service, The Royal Orthopaedic Hospital NHS Foundation TrustBackground</br>
Whilst the resection margin is an established factor predictive of local control of soft-tissue sarcomas (STSs), the adequacy of margin width for low-grade STSs has been rarely described. We aimed to investigate the margin adequacy and its prognostic relevance in low-grade STSs.</br>
Methods</br>
109 patients who underwent surgical treatment for a low-grade STS were studied. The prognostic value of margin status was evaluated according to the R–, R+1–classification, and width in millimetres.</br>
Results</br>
The 10-year local recurrence (LR) rates were 6%, 27%, 54% in R0, R1, and R2, respectively (p < 0.001), according to the R–classification. The R+1–classification resulted in a decreased LR rate in R1, but no major differences in LR rates in R0 and R2; 7%, 14%, 54% in R0, R1, and R2, respectively (p < 0.001). When classified by metric distance, 10-year LR rates were 0%, 8%, and 38% by ≥ 2.0 mm, 0.1–1.9 mm, and 0 mm margins, respectively (p < 0.001). Patients with close margins (0.1–1.9 mm) who received adjuvant radiotherapy had a trend toward lower LR risk than those without radiotherapy (10-year, 4% vs. 12%; p = 0.406). The 5 and 10-year disease-specific mortality was 9% and 13%, respectively; margin width was not associated with disease-specific mortality but LR was a poor prognostic factor for survival (p = 0.003).</br>
Conclusion</br>
Whilst negative margin provided local control over 90%, excellent local control was achieved with microscopic margins ≥2 mm. The role of margins is more important than radiotherapy in local control. Margins do not determine survival, but LR is associated with a poor prognosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1873-5061482020Generation of four induced pluripotent stem cell lines (FHUi003-A, FHUi003-B, FHUi004-A and FHUi004-B) from two affected individuals of a familial neurohypophyseal diabetes insipidus family101960ENSatoruYoshidaDepartment of Regenerative Medicine and Stem Cell Biology, Fujita Health University School of MedicineHanayukiOkuraDepartment of Regenerative Medicine Support Promotion Facility, Center for Research Promotion and Support, Fujita Health UniversityHidetakaSugaDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineMikaSoenDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineYoheiKawaguchiDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineJunkiKurimotoDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineTakashiMiyataDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineHiroshiTakagiDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineHiroshiArimaDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of MedicineTatsuyaFujikawaDepartment of General Internal Medicine, Mitoyo General HospitalFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry Pharmaceutical SciencesAkifumiMatsuyamaDepartment of Regenerative Medicine and Stem Cell Biology, Fujita Health University School of MedicineFour disease-specific induced pluripotent stem cell (iPSC) lines were respectively derived from peripheral blood mononuclear cells of two affected individuals in a family affected by familial neurohypophyseal diabetes insipidus carrying the c.314G>C mutation. The expression of pluripotency markers (NANOG, OCT4, and SOX2), maintenance of a normal karyotype, absence of episomal vectors used for iPSC generation, and presence of the original pathogenic mutation were confirmed for each iPSC line. The ability to differentiate into three germ layers was confirmed by a teratoma formation assay. These iPSC lines can help in disease recapitulation in vitro using organoids and elucidation of disease mechanisms.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0003267011352020On-site analysis of paraquat using a completely portable photometric detector operated with small, rechargeable batteries99106ENSasikarnSeetasangDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityTakashiKanetaDepartment of Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityThis work describes a methodology that can be used to achieve on-site analysis of paraquat in water samples by using a miniaturized portable photometer consisting of a couple of light-emitting diodes (LEDs). Paraquat produces a colored radical via a redox reaction with sodium dithionite, which is unstable against oxygen in solution. The steps taken to stabilize the reagent solution included control of the pH and the addition of organic solvents, but the most effective was the formation of an oil layer. Together, these steps stabilized the reagent solution for two days. An increase in the duration of reagent stability, however, is necessary in order to transport the reagent for on-site applications in remote locales. For the time being, an excess amount of solid sodium dithionite can be added directly to sample solutions because the unreacted dithionite shows no influence on absorbance of the paraquat radical. Orange LEDs with a maximum emission wavelength of 609 nm were employed in the portable photometer to measure the absorbance of paraquat radical produced by a redox reaction that has an absorption maximum of 603 nm. The developed photometer showed excellent performance with a linear range of from 2.0 mg L−1 to 40.0 mg L−1 and a linear regression (r2 = 1). The limits of detection and quantification were 0.5 mg L−1 and 1.5 mg L−1, respectively, intra-day precision (n = 3) and inter-day precision (n = 5) were both less than 5%, and accuracy based on the percentage of sample recovery ranged from 89 ± 0 to 105 ± 0% (n = 3). The proposed method was applied to the analysis of paraquat in water samples taken from rice fields. The results showed no paraquat in all thirteen samples, which could have been due to strong adsorption of paraquat by soil particles and/or to complications with the sampling conditions. To confirm the adsorption onto soil of paraquat contained in water, we constructed an artificial rice field where water containing paraquat was impounded above the soil layer. The results showed that paraquat in water gradually decreased within three days and could be measured in the soil on the fourth day. These results were confirmed by HPLC analysis, which underscores the utility of this portable photometer for the on-site monitoring of paraquat in water samples.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama002191503112020Identification and visualization of oxidized lipids in atherosclerotic plaques by microscopic imaging mass spectrometry-based metabolomics112ENLianhuaShenCollaborative Research Center (OMIC)TakushiYamamotoAnalytical & Measuring Instruments Division, Shimadzu CorporationXian WenTanDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKoretsuguOgataAnalytical & Measuring Instruments Division, Shimadzu CorporationEijiAndoAnalytical & Measuring Instruments Division, Shimadzu CorporationEiichiOzekiTechnology Research Laboratory, Shimadzu CorporationEijiMatsuuraDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground and aimsDysregulated lipid metabolism has emerged as one of the major risk factors of atherosclerosis. Presently, there is a consensus that oxidized LDL (oxLDL) promotes development of atherosclerosis and downstream chronic inflammatory responses. Due to the dynamic metabolic disposition of lipoprotein, conventional approach to purify bioactive lipids for subsequent comprehensive analysis has proven to be inadequate for elucidation of the oxidized lipids species accountable for pathophysiology of atherosclerotic lesions. Herein, we aimed to utilize a novel mass microscopic imaging technology, coupled with mass spectrometry (MS) to characterize oxidized lipids in atherosclerotic lesions. MethodsWe attempted to use MALDI-TOF-MS and iMScope to identify selected oxidized lipid targets and visualize their respective localizations in study models of atherosclerosis. ResultsBased on the MS analysis, detection of 7-K under positive ionization through product ion peak at m/z 383 [M+H-H2O] indicated the distinctive presence of targeted lipid within Cu2+-oxLDL and Cu2+-oxLDL loaded macrophage-like J774A.1 cell, along with other cholesterol oxidation products. Moreover, the application of two-dimensional iMScope has successfully visualized the localization of lipids in aortic atherosclerotic plaques of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Distinctive lipid distribution profiles were observed in atherosclerotic lesions of different sizes, especially the localizations of lysoPCs in atherosclerotic plaques. ConclusionsTaken together, we believe that both MALDI-TOF-MS and iMScope metabolomics technology may offer a novel proposition for future pathophysiological studies of lipid metabolism in atherosclerosis.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2666-478X12020Dicer monitoring in a model filamentous fungus host, Cryphonectria parasitica100001ENAnnisaAuliaInstitute of Plant Science and Resources, Okayama UniversityMidoriTabaraTokyo University of Agriculture and Technology, Department of Applied Biological SciencesPaulTelengechInstitute of Plant Science and Resources, Okayama UniversityToshiyukiFukuharaTokyo University of Agriculture and Technology, Department of Applied Biological SciencesNobuhiroSuzukiInstitute of Plant Science and Resources, Okayama UniversityThe ascomycete Cryphonectria parasitica has served as a model filamentous fungus for studying virus host interactions because of its susceptibility to diverse viruses, its genetic manipulability and the availability of many biological and molecular tools. Cryphonectria prasitica is known to activate antiviral RNA silencing upon infection by some viruses via transcriptional up-regulation of key RNA silencing genes. Here, utilizing a newly developed GFP-based reporter system to monitor dicer-like 2 (dcl2) transcript levels, we show different levels of antiviral RNA silencing activation by different viruses. Some viruses such as mycoreovirus 1, a suppressor-lacking mutant of Cryphonectria hypovirus 1 (CHV1-Δp69) and Rosellinia necatrix partitivirus 11 (RnPV11) highly induced RNA silencing, while others such as CHV3, Rosellinia necatrix victorivirus 1 and RnPV19 did not. There was considerable variation in dcl2 induction by different members within the family Hypoviridae with positive-sense single-stranded RNA genomes or Partitiviridae with double-stranded RNA genomes. Northern blotting and an in vitro Dicer assay developed recently by us using mycelial homogenates validated the reporter assay results for several representative virus strains. Taken together, this study represents a development in the monitoring of Dicer activity in virus-infected C. parasitica.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2213-0071312020Pediatric airway compromise due to thyroid storm associated with influenza A infection: A case report101182ENTaikiHigakiDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesKoheiTsukaharaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakafumiObaraDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHirotsuguYamamotoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesTakaakiOsakoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesHiromichiNaitouDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical SciencesThyroid storm is a potentially fatal intensification of thyrotoxicosis normally marked by tachycardia, hyperthermia, impaired mental status, and severe agitation. It can be initiated by numerous causes. Failure to promptly diagnose the condition may lead to high mortality. Early diagnosis and treatment of thyroid storm are essential to prevent further life-threatening complications. A 10-year-old girl was admitted to our emergency center for intensive care. The patient presented tachypnea with stridor, paradoxical abdominal breathing, and “barking” cough. The patient was diagnosed as upper airway obstruction complicated by thyroid storm associated with influenza infection. Following immediate airway management, the patient was administered a short-acting beta-blocker, hydrocortisone, thiamazole, and saturated solution of potassium iodide was initiated. The patient was extubated on day 8 and transferred to a local hospital on day 11 without adverse complications. When examining patients with influenza infection, emergency doctors should be more attentive not to miss other critical diagnoses. The present case was initially diagnosed as croup due to influenza infection. Sharing our experience may help emergency physicians treat similar cases of pediatric airway compromise due to thyroid storm.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612732020Pulmonary resection for metachronous metastatic gastric cancer diagnosed using multi-detector computed tomography: Report of five cases342346ENNoriyukiNishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHideakiKojimaDivision of Thoracic Surgery, Shizuoka Cancer CenterMitsuhiroIsakaDivision of Thoracic Surgery, Shizuoka Cancer CenterEtsuroBandoDivision of Gastric Surgery, Shizuoka Cancer CenterMasanoriTerashimaDivision of Gastric Surgery, Shizuoka Cancer CenterYasuhisaOhdeDivision of Thoracic Surgery, Shizuoka Cancer CenterIntroduction</br>
As pulmonary resection for metastatic gastric cancer has been rarely reported on, the role of metastasectomy remains unclear in such settings. We reviewed the clinicopathological characteristics and surgical outcomes of patients with metachronous pulmonary metastasis from gastric cancer (MPMGC) diagnosed using multi-detector computed tomography (MDCT) who underwent pulmonary resection.</br>
Presentation of case</br>
From September 2002 to May 2018, five patients underwent pulmonary resection for MPMGC at Shizuoka Cancer Center. All patients received curative resection for initial gastric cancer. Three patients received adjuvant chemotherapy. The median age at pulmonary resection was 70 years. The median disease-free interval between initial gastrectomy and MPMGC diagnosis was 41 months. The first site of recurrence was the lung in all patients. All patients were diagnosed as having primary lung cancer using MDCT before pulmonary resection and fit the surgical indication for primary lung cancer. Lobectomy was performed in three patients, while wedge resection was performed in two. The median overall survival following pulmonary resection was 79 (range, 18–89) months. Two patients experienced recurrence. While one showed recurrence in the mediastinal lymph node, in the other it was observed in the remnant lung; the latter underwent repeated pulmonary resection followed by systemic chemotherapy. Four patients survived for longer than 4 years after pulmonary resection.</br>
Conclusions</br>
Of the five patients with MPMGC diagnosed using MDCT who underwent pulmonary resection, long-term survival was achieved after pulmonary resection in four. Thus, pulmonary resection may be considered for those diagnosed with lung nodules after surgery for gastric cancer, and who fit the surgical indication for primary lung cancer.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2210-2612732020Laparoscopic liver resection of segment seven: A case report and review of surgical techniques168171ENKoseiTakagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakashiKuiseDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuzoUmedaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyuichiYoshidaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesFuminoriTeraishiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakahitoYagiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshiyoshiFujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesIntroduction</br>
Laparoscopic liver resection of segment seven (LLR-S7) is a technically challenging procedure due to its anatomical location and difficult accessibility. Herein, we present our experience with LLR-S7, and demonstrate a literature review regarding surgical techniques.</br>
Presentation of case</br>
A 28-year-old female was diagnosed with rectosigmoid cancer and synchronous liver metastases at the segment three (S3) and S7, which were treated with laparoscopic procedure. After the completely mobilization of the right lobe, the Glissonean pedicle of S7 (G7) was intrahepatically transected. The right hepatic vein was exposed to identify the venous branch of S7 (V7). Finally the liver parenchyma between RHV and dissection line was divided.</br>
Discussion</br>
Various laparoscopic approaches for S7 have been reported including the Glissonian approach from the hilum, the intrahepatic Glissonean approach, the caudate lobe first approach, and the lateral approach from intercostal ports. To perform LLR-S7 safely, it is important to understand the advantage of each technique including the trocar placement and approaches to S7 by laparoscopy.</br>
Conclusion</br>
We present our experience of LLR-S7 for the tumor located at the top of S7, successfully performed with the intrahepatic Glissonean approach. LLR-S7 can be performed safely with advanced laparoscopic techniques and sufficient knowledge on various approaches for S7.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0927-77575202017Indocyanine green-laden poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules incorporating reverse micelles: Effects of PEG-b-PLA composition on the nanocapsule diameter and encapsulation efficiency764770ENTakaichiWatanabeDepartment of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityYuiSakamotoDepartment of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityTetsuyaInookaDivision of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityYukitakaKimuraDivision of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama UniversityTsutomuOnoDepartment of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama UniversityReverse micelles are thermodynamically stable systems, with a capacity to encapsulate hydrophilic molecules in their nanosized core, which is smaller than the core generally obtained with water-in-oil-emulsion droplets. Herein, we present a simple technique for the preparation of poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules encapsulating a hydrophilic photosensitizer (indocyanine green, ICG), which exploits reverse micelle formation and subsequent emulsion-solvent diffusion. We establish the effect of the PEG-b-PLA composition and the co-surfactant volume on the diameter and water content of the reverse micelles. We demonstrate that the composition of PEG-b-PLA affects also the diameter and encapsulation efficiency of the resulting nanocapsules. We show that the ICG-laden nanocapsules fabricated under the most optimal conditions have a diameter of approximately 100 nm and an ICG encapsulation efficiency of 58%. We believe that the method proposed here is a promising step towards the preparation of hydrophilic drug-laden polymer nanocapsules with a small diameter and therefore suitable for use in drug delivery applications based on enhanced permeability and retention (EPR) effect-driven passive targeting.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2405-8440652020Impact of heavy rains of 2018 in western Japan: disaster-induced health outcomes among the population of Innoshima Islande03942ENSrinivasBandaruDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShunjiSanoDepartment of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San FranciscoYurikaShimizuDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYukaSekiDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikazuOkanoHitz Hitachi Zosen Health Insurance Association Clinic at InnoshimaTamakiSasakiDepartment of Nephrology & Hypertension, Kawasaki Medical SchoolHidehoWadaDepartment of Hematology, Kawasaki Medical SchoolTakemiOtsukiDepartment of Hygiene, Kawasaki Medical SchoolTatsuoItoDepartment of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesSouthwestern Japan suffered its worst rains in 2018 causing floods and mudslides, claiming 225 lives and forcing millions for evacuations. Referred as "Heisei san-ju-nenshichi-gatsugou", the disaster was the result of incessant precipitation caused by the interaction of typhoon "Prapiroon" with the seasonal rain front "Baiu". The present epidemiological study aims to investigate disaster-induced health issues in 728 residents of Innoshima island in the Hiroshima Prefecture by comparing their clinical data in pre-disaster (2017) and disaster-hit (2018) years which was obtained from annual health screening. Comparison of data showed a significant increase in the urine protein concentration in victims following the disaster. Probing further into the household conditions, showed that a total of 59,844 households were affected with water outage during the heavy rains, which was accompanied by severe damage of sewerage pipelines with complete recovery process taking two weeks. This two weeks of the crisis forced victims to refrain from using restrooms which in turn led to infrequent urination, thereby explaining the increased urine protein concentration in victims following the disaster. The present study addresses the acute health implications caused by the water crisis and serves as a precautionary measure for disaster management council to provide enhanced aftercare services in victims in further events of natural disasters. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0300-95721532020Improved outcomes for out-of-hospital cardiac arrest patients treated by emergency life-saving technicians compared with basic emergency medical technicians: A JCS-ReSS study report251257ENHiromichiNaitouHiromichi TetsuyaYumotoOkayama University HospitalTakashiYorifujiOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshioTaharaNational Cerebral and Cardiovascular Center, Department of Cardiovascular MedicineNaohiroYonemotoNational Center of Neurology and PsychiatryHiroshiNonogiShizuoka General Hospital, Intensive Care CenterKenNagaoNihon University Hospital, Cardiovascular CenterTakanoriIkedaToho University Faculty of Medicine, Department of Cardiovascular MedicineNaokiSatoKawaguchi Cardiovascular and Respiratory Hospital, Cardiovascular MedicineHiroyukiTsutsuiKyushu University Faculty of Medical Sciences, Department of Cardiovascular MedicineBackground</br>
Emergency life-saving technicians (ELSTs) are specially trained prehospital medical providers believed to provide better care than basic emergency medical technicians (BEMTs). ELSTs are certified to perform techniques such as administration of advanced airways or adrenaline and are considered to have more knowledge; nevertheless, ELSTs’ effectiveness over BEMTs regarding out-of-hospital cardiac arrest (OHCA) remains unclear. We investigated whether the presence of an ELST improves OHCA patient outcomes.</br>
Methods</br>
In a retrospective study of adult OHCA patients treated in Japan from 2011 to 2015, we compared two OHCA patient groups: patients transported with at least one ELST and patients transported by only BEMTs. The primary outcome measure was one-month favorable neurological outcomes, defined as Cerebral Performance Category ≤ 2. A multivariable logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs) to evaluate the effect of ELSTs.</br>
Results</br>
Included were 552,337 OHCA patients, with 538,222 patients in the ELST group and 14,115 in the BEMT group. The ELST group had a significantly higher odds of favorable neurological outcomes (2.5% vs. 2.1%, adjusted OR 1.39, 95% CI 1.17–1.66), one-month survival (4.9% vs. 4.1%, adjusted OR 1.37, 95% CI 1.22–1.54), and return of spontaneous circulation (8.1% vs. 5.1%, adjusted OR 1.90, 95% CI 1.72–2.11) compared with the BEMT group. However, ELSTs’ limited procedure range (adrenaline administration or advanced airway management) did not promote favorable neurological outcomes.</br>
Conclusions</br>
Compared with the BEMT group, transport by the ELST group was associated with better neurological outcomes in OHCA.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0921-50937912020The effect of precipitations (NbC and carbide) in Fe–C–Mn-xNb steels on hydrogen embrittlement characteristics139598ENMitsuhiroOkayasuGraduate School of Natural Science and Technology, Okayama UniversityMasayaSatoGraduate School of Natural Science and Technology, Okayama UniversityDaikiIshidaGraduate School of Natural Science and Technology, Okayama UniversityTakehideSenumaGraduate School of Natural Science and Technology, Okayama UniversityHydrogen embrittlement (HE) characteristics in Fe–C–Mn-xNb steels were examined via various analyses, including electron backscatter diffraction analysis, scanning transmission electron microscopy and three-dimensional atom-probe tomography. For the investigation, the steel samples were prepared with varying Nb contents and heat treatment processes. The material properties of steel samples that were subjected to: (i) water quenching and (ii) quenching and tempering at 170 °C for 20 min, were determined to be nearly similar, although different degrees of HE were detected. After the tempering process, ε-carbide precipitated clearly in the matrix, which could act as a trapping site for hydrogen atoms and lead to improved HE resistance. Moreover, with addition of Nb, niobium base precipitates (e.g., NbC) with a diameter of a few nanometers were obtained in the martensite matrix, which could also function as hydrogen trapping sites. There was slight improvement in the HE resistance with NbC. Hydrogen-assisted failure mechanisms under both static and cyclic loading were observed with intergranular brittle cracking for the water quenched sample, even though the brittle and ductile mix failure mode was detected for the sample after the quenching and tempering process.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama2352-3409302020Dataset for de novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus105388ENNaokiYoshidaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityChikaraKaitoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityIn this article, we report the first de novo transcriptome assembly of the African bullfrog Pyxicephalus adspersus. In this data, 75,320,390 raw reads were acquired from African bullfrog mRNA using Illumina paired-end sequencing platform. De novo assembly resulted in a total of 136,958 unigenes. In the obtained unigenes, 30,039 open reading frames (ORFs) were detected. This dataset provides basic information for molecular level analysis of this species, which undergoes a state of dormancy under dry conditions at ordinary temperatures called estivation. No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1877-056810632020Transtibial pullout repair of the lateral meniscus posterior root tear combined with anterior cruciate ligament reconstruction reduces lateral meniscus extrusion: A retrospective study469473ENYukiOkazakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakayukiFurumatsuDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYusukeKamatsukiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYoshikiOkazakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinMasudaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesTakaakiHiranakaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesYuyaKodamaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesShinichiMiyazawaDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground</br>
Lateral meniscus (LM) posterior root tear (PRT) is often associated with anterior cruciate ligament (ACL) injury and can result in rotational instability, joint overloading, and degenerative changes in the knee. Improved rotational stability and kinematics have been reported after LMPRT repair. However, it is unclear what repair technique can achieve the greatest reduction in LM extrusion (LME).</br>
Hypothesis</br>
We hypothesized that transtibial pullout repair would decrease LME to a greater extent than other repair techniques.</br>
Patients and methods</br>
Seventeen patients with ACL injury and complete LMPRT were evaluated. Nine underwent ACL reconstruction (ACLR) and transtibial pullout repair, and eight underwent ACLR and other repairs such as inside-out suturing. Double-bundle ACLR was performed using hamstring tendons, and LMPRT pullout repair was performed through the bone tunnel for the posterolateral bundle. Magnetic resonance imaging was performed immediately preoperatively and at > 6 months postoperatively, and LME was measured from coronal images only.</br>
Results</br>
A significantly greater decrease in the value of LME from pre- to postoperative measurement was observed in the transtibial pullout repair group (−0.5 ± 0.7 mm) than in the other-repair group (1.0 ± 0.9 mm, p < 0.01). Pre- and postoperative LME measurements were not significantly different between the two groups.</br>
Discussion</br>
The most important finding of this study was that transtibial pullout repair resulted in a greater decrease in LME than other repair techniques in patients with ACL injury and LMPRT. This technique might be useful for restoring hoop tension by decreasing LME.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0142-96122512020Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements120077ENHiroyoshi Y.TanakaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTsuyoshiKuriharaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakuyaNakazawaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMichiyaMatsusakiDepartment of Applied Chemistry, Graduate School of Engineering, Osaka UniversityAtsushiMasamuneDivision of Gastroenterology, Graduate School of Medicine, Tohoku UniversityMitsunobu R.KanoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityPancreatic ductal adenocarcinoma (PDAC) is an often lethal disease characterized by a dense, fibrotic stroma. However, the lack of relevant preclinical models that recapitulate the characteristic histopathology of human PDAC in vitro impedes the development of novel therapies. The amount of stromal elements differ largely within and between patients, but in vitro models of human PDAC often do not account for this heterogeneity. Indeed, analyses of human PDAC histopathology revealed that the proportion of stroma ranged from 40 to 80% across patients. We, therefore, generated a novel 3D model of human PDAC, consisting of co-cultured human PDAC tumor cells and fibroblasts/pancreatic stellate cells, in which the proportion of fibrotic elements can be tuned across the clinically observed range. Using this model, we analyzed the signaling pathways involved in the differentiation of myofibroblasts, a characteristic subpopulation of fibroblasts seen in PDAC. We show that both YAP and SMAD2/3 in fibroblasts are required for myofibroblastic differentiation and that both shared and distinct signaling pathways regulate the nuclear localization of these factors during this process. Our novel model will be useful in promoting the understanding of the complex mechanisms by which the fibrotic stroma develops and how it might be therapeutically targeted.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0142-96121922018Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness355367ENHiroyoshi Y.TanakaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKentaroKitaharaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityNaokiSasakiDepartment of Chemical and Biological Sciences, Japan Women's UniversityNatsumiNakaoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKaeSatoDepartment of Chemical and Biological Sciences, Japan Women's UniversityHirokazuNaritaDepartment of Anatomical Science, Hirosaki University Graduate School of MedicineHiroshiShimodaDepartment of Anatomical Science, Hirosaki University Graduate School of MedicineMichiyaMatsusakiDepartment of Frontier Biosciences, Osaka University Graduate School of Frontier BiosciencesHiroshiNishiharaGenomics Unit, Keio Cancer Center, Keio University School of Medicine, Institute of Integrated Medical ResearchAtsushiMasamuneDivision of Gastroenterology, Tohoku University Graduate School of MedicineMitsunobu R.KanoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityDesmoplasia is a hallmark of pancreatic cancer and consists of fibrotic cells and secreted extracellular matrix (ECM) components. Various in vitro three-dimensional (3D) models of desmoplasia have been reported, but little is known about the relevant thickness of the engineered fibrotic tissue. We thus measured the thickness of fibrotic tissue in human pancreatic cancer, as defined by the distance from the blood vessel wall to tumor cells. We then generated a 3D fibrosis model with a thickness reaching the clinically observed range using pancreatic stellate cells (PSCs), the main cellular constituent of pancreatic cancer desmoplasia. Using this model, we found that Collagen fiber deposition was increased and Fibronectin fibril orientation drastically remodeled by PSCs, but not normal fibroblasts, in a manner dependent on Transforming Growth Factor (TGF)-β/Rho-Associated Kinase (ROCK) signaling and Matrix Metalloproteinase (MMP) activity. Finally, by targeting Secreted Protein, Acidic and Rich in Cysteine (SPARC) by siRNA, we found that SPARC expression in PSCs was necessary for ECM remodeling. Taken together, we developed a 3D fibrosis model of pancreatic cancer with a clinically relevant thickness and observed aberrant SPARC-dependent ECM remodeling in cancer-derived PSCs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0168-36592302016Increased fibrosis and impaired intratumoral accumulation of macromolecules in a murine model of pancreatic cancer co-administered with FGF-2109115ENSatoshiSakaiGraduate School of Medicine, The University of TokyoCanameIwataGraduate School of Medicine, The University of TokyoHiroyoshi Y.Tanaka Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHoracioCabralGraduate School of Engineering, The University of TokyoYasuyukiMorishitaGraduate School of Medicine, The University of TokyoKoheiMiyazonGraduate School of Medicine, The University of TokyoMitsunobu R.KanoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityPancreatic cancer is notorious for its poor prognosis. The histopathologic characteristic of pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer, is fibrosis within tumor tissue. Although fibrosis within tumor tissue is thought to impede drug therapy by interfering with the intratumoral accumulation of anti-tumor drugs, this hypothesis has yet to be proven directly in preclinical models. Here, we evaluated the effect of enhanced fibrosis on intratumoral accumulation of macromolecular drugs by increasing fibrosis in a murine tumor model of subcutaneously xenografted BxPC-3, a human PDAC cell line. When fibroblast growth factor-2 (FGF-2) was co-administered upon BxPC-3 inoculation, stromal fibrotic area was increased and was characterized by augmented murine collagen accumulation compared to inoculation of BxPC-3 alone, which correlated with increased monocyte/macrophage contents in the tumor tissues. We further discovered that the intratumoral accumulation of intravenously administrated fluorescein isothiocyanate-dextran of 2,000,000 Da (2 MDa) was significantly reduced in the FGF-2 co-administered tumors despite unaltered hyaluronan accumulation and pericyte coverage of the tumor neovasculature and increased lymphangiogenesis. Finally, we found that FGF-2 co-administered tumors are more refractory to macromolecular drug therapy using nab-paclitaxel (Abraxane). The model established and analyzed in this study, characterized by increased fibrotic component, provides a preclinical animal model suited to predict the intratumoral accumulation of macromolecular drugs and to evaluate the efficacy of drugs targeting the tumor stroma.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0387-76044092018Differential diagnosis of nonepileptic twilight state with convulsive manifestations after febrile seizures781785ENHiroyukiMiyaharaDepartment of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomoyukiAkiyamaDepartment of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiWakiDepartment of Pediatrics, Kurashiki Central HospitalYoshioArakakiDepartment of Pediatrics, Kurashiki Central HospitalBackground</br>
Nonepileptic twilight state with convulsive manifestations (NETC) is a nonepileptic state following a febrile seizure (FS), which may be misdiagnosed as a prolonged seizure and result in overtreatment. We aimed to describe clinical manifestations of NETC and to determine characteristics that are helpful to distinguish NETC from other pathological conditions.</br>
Methods</br>
We conducted a retrospective chart review from January 2010 to December 2016 and selected the patients who presented with symptoms resembling status epilepticus with fever and a confirmed diagnosis using an electroencephalogram (EEG). We compared the NETC clinical features and venous blood gas analysis results with those of other conditions that mimic NETC. We also compared the characteristics of NETC with past reports.</br>
Results</br>
Our NETC patients presented with short durations of the preceding generalized convulsions followed by tonic posturing, closed eyes, no cyanosis, responsiveness to painful stimulation, and no accumulation of CO2 in the venous blood gas. Most of these characteristics were consistent with past reports. Prolonged FS or acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) showed several of these features, but all the characteristics were not consistent with our study.</br>
Conclusions</br>
Prolonged FS and AESD need to be differentiated from NETC, and close clinical observation makes it possible to partially distinguish NETC from the other conditions. EEG is recommended for patients with symptoms that are inconsistent with these features.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama221253455832020Deterioration of high-resolution computed tomography findings predicts disease progression after initial decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone185189ENHisaoHigoOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNobuakiMiyaharaOkayama University HospitalAkihikoTaniguchiOkayama University HospitalSatoruSenooOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesJunkoItanoOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiromiWatanabeOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesNaohiroOdaOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesHiroeKayataniNational Hospital Organization Okayama Medical CenterHirohisaIchikawaKKR Takamatsu HospitaTakuoShibayamaNational Hospital Organization Okayama Medical CenterKazuhiroKajimotoKobe Red Cross HospitalYasushiTanimotoNational Hospital Organization Minami-Okayama Medical CenterArihikoKanehiroOkayama Rosai HospitalYoshinobuMaedaOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKatsuyukiKiuraOkayama University Hospital OKAYAMA respiratory disease study group (ORDSG)Background</br>
Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline.</br>
Methods</br>
This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled.</br>
Results</br>
We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009).</br>
Conclusions</br>
We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0012821X5302019Grain boundary diffusion of W in lower mantle phase with implications for isotopic heterogeneity in oceanic island basalts by core-mantle interactions115887ENTakashiYoshinoInstitute for Planetary Materials, Okayama UniversityYoshikiMakinoGeochemical Research Center, The University of TokyoToshihiroSuzukiGeochemical Research Center, The University of TokyoTakafumiHirataGeochemical Research Center, The University of TokyoTungsten isotopes provide important constraints on the ocean-island basalt (OIB) source regions. Recent analyses of μ182W in modern basalts with high 3He/4He originating from the core-mantle boundary region reveal two distinct features: positive μ182W in Phanerozoic flood basalts indicating the presence of primordial reservoir, and negative μ182W in modern OIBs. One possibility to produce large variations in μ182W is interaction between the mantle and outer core. Here, we report grain boundary diffusion of W in lower mantle phases. High pressure experimental results show that grain boundary diffusion of W is fast and strongly temperature dependent. Over Earth's history, diffusive transport of W from the core to the lowermost mantle may have led to significant modification of the W isotopic composition of the lower mantle at length scales exceeding one kilometer. Such grain boundary diffusion can lead to large variations in μ182W in modern basalts as a function of the distance of their source regions from the core mantle boundary. Modern oceanic island basalts from Hawaii, Samoa and Iceland exhibit negative μ182W and likely originated from the modified isotope region just above the core-mantle boundary, whereas those with positive μ182W could be derived from the thick Large Low Shear Velocity Provinces (LLSVPs) far from the core-mantle boundary (CMB). When highly-oxidized slabs accumulate at the CMB oxidizing the outer core at the interface, a large W flux with negative μ182W can be added to the silicate mantle. As a result, the source region of the OIB would be effectively modified to a negative μ182W.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama003808066012020Disaster report of 2018 July heavy rain for geo-structures and slopes in Okayama300314ENS.NishimuraOkayama UniversityY.TakeshitaOkayama UniversityS.NishiyamaOkayama UniversityS.SuzukiOkayama UniversityT.ShibataOkayama UniversityT.ShukuOkayama UniversityM.KomatsuOkayama UniversityB.KimOkayama UniversityIn July 2018, heavy rain and a large amount of damage to geo-structures and natural slopes were reported in Okayama, Japan. In particular, in the area surrounding the Oda River System, 52 people drowned due to the breach of river banks. Besides the flooding of rivers, the earth-fill dams of many water reservoirs were damaged. The stability of the large number of earth-fill dams in the Setouchi area is very important. Heavy rain is often associated with the collapse of slopes. In Okayama, many shallow slope failures or debris flows occurred over a wide area, particularly in the western part of the prefecture. Through detailed investigations, the mechanism of this geo-disaster was clarified.No potential conflict of interest relevant to this article was reported.