Wiley Acta Medica Okayama 2688-4526 7 2 2026 Safety and efficacy of Rezūm water vapour energy therapy in BPH patients receiving antithrombotic therapy: A Japanese single‐centre experience e70170 EN Takatoshi Moriwake Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruki Kaku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ichiro Tsuboi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Katayama Department of Urology, Okamura Isshindo Hospital Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The objective of this study is to evaluate the safety and efficacy of Rezūm water vapour energy therapy (WAVE) in Japanese patients with benign prostatic hyperplasia (BPH) continuing antithrombotic therapy and to validate the Okayama University Modified Clavien-Dindo classification (OU-mCD) for perioperative hematuria. Patients and Methods: We retrospectively analysed 80 consecutive patients who underwent WAVE from August 2023 to July 2024, including 37 (46.2%) continuing antithrombotic therapy perioperatively. Hematuria within 30 days was graded using conventional Clavien-Dindo classification and the OU-mCD, a novel classification focusing on intervention necessity. We assessed clinically significant hematuria (Grade ≥ Ib), catheter-free rate, prostate volume reduction and haemoglobin change. Results: Clinically significant hematuria occurred in 21.6% (8/37) of patients continuing antithrombotic therapy versus 4.7% (2/43) without (p = 0.038). All 10 Grade ≥ Ib cases occurred during hospitalization with the catheter in place and were managed conservatively with continuous bladder irrigation (median 1 day); none required transfusion or surgical reintervention. Only one patient required temporary drug discontinuation. Treatment efficacy did not differ by antithrombotic status: 86.2% achieved PVR < 50 ml with 44% mean prostate volume reduction. Multivariate analysis identified antithrombotic therapy as the sole independent risk factor for Grade ≥ Ib hematuria (OR 5.46, 95% CI 1.06–28.16, p = 0.042). Conclusion: WAVE can be safely performed with continued antithrombotic therapy. Whereas Grade ≥Ib hematuria occurred in 25% of antiplatelet/anticoagulant users (vs. 5% without), 75% had no significant bleeding, and all complications were managed conservatively without transfusion. The OU-mCD provides precise complication stratification. These findings suggest outpatient procedures may be feasible with appropriate patient selection. No potential conflict of interest relevant to this article was reported.

American Medical Association (AMA) Acta Medica Okayama 2574-3805 8 11 2025 Trastuzumab Deruxtecan for ERBB2-Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases: A Secondary Analysis of Randomized Clinical Trials e2543107 EN Pasi A. Jänne Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute David Planchard Department of Medical Oncology, Thoracic Cancer Group, Gustave Roussy, Medical Oncology Koichi Goto Department of Thoracic Oncology, Nation Cancer Center Hospital East Egbert F. Smit Department of Pulmonary Diseases, Leiden University Medical Center Adrianus Johannes de Langen Department of Thoracic Oncology, Netherlands Cancer Institute Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Maurice Pérol Department of Medical Oncology, Centre Léon Bérard Enriqueta Felip Department of Medical Oncology, Vall d’Hebron University and Vall d’Hebron Institute of Oncology Hidetoshi Hayashi Department of Medical Oncology, Kindai University Faculty of Medicine Kazuhiko Nakagawa Department of Medical Oncology, Kindai University Faculty of Medicine Junichi Shimizu Department of Thoracic Oncology, Aichi Cancer Center Misako Nagasaka Division of Hematology-Oncology, Department of Medicine, University of California Irvine Kaline Pereira Daiichi Sankyo Inc Ayumi Taguchi Daiichi Sankyo Co Ltd Ahmed Ali Daiichi Sankyo Europe GmbH Maha Karnoub Daiichi Sankyo Inc Rie Yonemochi Daiichi Sankyo Inc David Leung Daiichi Sankyo Inc Bob T. Li Thoracic Oncology and Early Drug Development Service, Global Research Program, Memorial Sloan Kettering Cancer Center Importance Brain metastases reduce overall survival rates of patients with non–small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])–mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC. Objective To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases. Design, Setting, and Participants This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024. Intervention Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks. Main Outcome and Measure Systemic and intracranial effectiveness by blinded independent central review using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1, sites of progression, and safety. Results This analysis included 102 patients in the T-DXd 5.4-mg/kg dose group (65 females [64%]; median [range] age, 57.5 [37.0-83.0] years and 59.5 [30.0-79.0] years in patients with and without brain metastases, respectively) and 141 patients in the T-DXd 6.4-mg/kg dose group (94 females [67%]; median [range] age, 62.5 [29.0-88.0] years and 59.0 [27.0-83.0] years in patients with and without brain metastases, respectively). In each group, 31% (32 of 102) and 38% (54 of 141) of patients, respectively, had baseline brain metastases and 53% (17 of 32) and 44% (24 of 54), respectively, received prior brain metastasis treatment. In patients with and without brain metastases, systemic confirmed objective response rates (ORRs) were 47% (15 of 32; 95% CI, 29%-65%) and 50% (35 of 70; 95% CI, 38%-62%), respectively, with the T-DXd 5.4-mg/kg dose, and 50% (27 of 54; 95% CI, 36%-64%) and 59% (51 of 87; 95% CI, 48%-69%) with the T-DXd 6.4-mg/kg dose. Median progression-free survival was 7.1 (95% CI, 5.5-9.7) months in the T-DXd 5.4-mg/kg dose group and 7.1 (95% CI, 4.5-9.6) months in the T-DXd 6.4-mg/kg dose group of patients with baseline brain metastases. Among patients with measurable baseline brain metastases, intracranial confirmed ORRs were 50% (7 of 14; 95% CI, 23%-77%) with the T-DXd 5.4-mg/kg dose and 30% (9 of 30; 95% CI, 15%-49%) with the T-DXd 6.4-mg/kg dose. At both doses, the safety profile of T-DXd was generally manageable, regardless of baseline brain metastases, favoring the T-DXd 5.4 mg/kg dose. Conclusions and Relevance In this secondary analysis, T-DXd at the approved dose of 5.4 mg/kg showed antitumor activity in patients with previously treated ERBB2-mutant metastatic NSCLC with or without brain metastases. This finding supports T-DXd 5.4 mg/kg use in this population. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0309-0167 88 5 2025 Claudin-18 expression in gastric type adenocarcinoma and HPV-associated adenocarcinoma of the uterine cervix 1003 1015 EN Nobuko Yasutake Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yuki Yokawa Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Takehiro Tanaka Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Riri Mishima Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Misato Komamizu Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University Fukuoka Japan Ryosuke Kuga Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Rina Jiromaru Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Shinichiro Kawatoko Department of Medicine and Clinical Science, Kyushu University Beppu Hospital Kenzo Sonoda Department of Gynecology, Kyushu University Beppu Hospital Hideaki Yahata Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Kiyoko Kato Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University Yoshinao Oda Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University Hidetaka Yamamoto Department of Pathology and Oncology, Graduate School of Medicine, Dentistry & Pharmaceutical Science, Okayama University Aims: Claudin-18 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43-14A antibody, or about the gene expression of its isoforms in ECAs. Methods and results: We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high-risk human papillomavirus (HR-HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV-independent adenocarcinomas (gastric type [GAS], n = 24; non-GAS, n = 11) and 86 HPV-associated ECAs. We also analysed mRNA expression of the CLDN18.1 (lung type) and CLDN18.2 (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8/24 (33%) GASs, 0/11 (0%) non-GASs and 2/86 (2%) HPV-associated ECAs, with positivity defined as staining in ≥75% of tumour cells, as in gastric cancer. When a 5% cut-off was used, CLDN18 positivity was detected in 22/24 (92%) GASs, 0/11 (0%) non-GASs and 6/86 (7%) HPV-associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (P < 0.0001). Among the 6 cases of HPV-associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV-associated ECAs. Six of 22 (27%) CLDN18-positive GASs were also positive for p16, but their other features―such as CLDN18 expression and the Rb preserved pattern―were the same as in p16 negative GASs. Expression of CLDN18.2 mRNA but not CLDN18.1 mRNA was confirmed in both GASs and HPV-associated ECAs. Conclusions: CLDN18 (43-14A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV-associated ECAs also can be immunoreactive for CLDN18 and express CLDN18.2 mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV-associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Kinesiophobia Is Associated with Disability, Poor Quality of Life, Psychological Morbidity, and Surgery Dissatisfaction in Patients with Lumbar Microdiscetomy: A Cross-Sectional Controlled Study 39 46 EN Nihal Tezel Department of Physical and Rehabilitation Medicine, Health Sciences University Aslı Gençay Can Department of Physical and Rehabilitation Medicine, Faculty of Medicine, Ankara Yıldırım Beyazıt University Original Article 10.18926/AMO/70071 The study aimed to determine the prevalence of kinesiophobia in patients who had undergone lumbar microdiscectomy and to examine its associations with pain intensity, disability, quality of life, depression, anxiety, and satisfaction with surgery. Forty-eight patients with microdiscectomy and 48 healthy controls were enrolled. The Tampa Scale for Kinesiophobia (TSK), Roland-Morris Disability Index (RMDI), Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and Short Form-36 Health Survey (SF-36) were administered to both groups. The scores of TSK, RMDI, HADS-A, and HADS-D were significantly higher and SF-36 scores were significantly lower in the microdiscectomy than the control group (p<0.001 for all). In the microdiscectomy group, median (min-max) RMDI, HADS-A, and HADS-D scores were 19 (4-34), 10 (0-18), and 9 (0-18), respectively, in kinesiophobic patients, and were significantly higher than 6 (2-20), 3 (0-11), 2.5 (0-11) in non-kinesiophobic patients (all p<0.001). The median (min-max) SF-36 PCS, SF-36 MCS, and VAS scores for surgery satisfaction were 36.5 (8.7-75), 52.1 (11-95), 5, 5 (0-10), respectively, in kinesiophobic patients and were significantly lower than 71 (28-95), 85.5 (9-93), 8.5 (3-10) in non-kinesiophobic patients (all p<0.05). TSK scores were significantly correlated with RMDI, HADS-A, HADS-D, SF-36, and surgery satisfaction scores (all p<0.05). Kinesiophobic patients with lumbar microdiscectomy therefore showed greater disability and psychological morbidity, poorer quality of life, and lower satisfaction with surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 A Novel Nomogram that Predicts Chronic Hemodialysis Patients’ Survival Based on Their Sedentary Behavior 9 16 EN Kentaro Sugahara Department of Hygiene, Faculty of Medicine, Kagawa University Takashi Kondo Innoshima General Hospital Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiroyuki Nishi Innoshima General Hospital Kazuhiro Ujike Innoshima General Hospital Kiichi Koumoto Innoshima General Hospital Keiichi Namio Department of Hygiene, Faculty of Medicine, Kagawa University Shuhei Hishii Department of Hygiene, Faculty of Medicine, Kagawa University Akihiko Katayama Faculty of Social Studies, Shikokugakuin University Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Yorimasa Yamamoto Innoshima General Hospital Original Article 10.18926/AMO/70068 Appropriate treatments for chronic hemodialysis patients are a public health challenge in Japan. Sedentary behavior appears to be closely associated with these patients’ survival. We thus sought to develop a nomogram that predicts survival based on the duration of chronic hemodialysis patients’ sedentary behavior. One hundred twenty-four patients under chronic hemodialysis (73 men, 51 women, age 71.7±11.1 years) were enrolled in this cohort study. The patients wore a triaxial accelerometer that measured both their sedentary behavior, i.e., total sedentary behavior (minutes) and their maximum sedentary bouts (min) on non-hemodialysis days. We obtained the Kaplan-Meier curve and used the log-rank test and a Cox proportional hazards model to evaluate the relationship between the patients’ sedentary behavior and their survival. We also used a Cox proportional hazards model to develop a nomogram for the patients’ 5-year survival rate. Forty-six patients died during the follow-up period. When we stratified the patients by the medians of total sedentary behavior and maximum sedentary bouts, we observed significant between-group differences. After adjustment for confounding factors in a Cox proportional hazards model, total sedentary behavior and maximum sedentary bouts were identified as critical survival factors, and we generated a nomogram using an index of sedentary behavior. Our analysis results demonstrated that sedentary behavior on non-dialysis days was closely associated with the survival of the chronic hemodialysis patients, suggesting that a decrease in sedentary behavior would prolong their survival. The nomogram developed herein based on sedentary behavior may be useful for predicting the outcomes of chronic hemodialysis patients. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 70 1 2006 Synthesis of 6- and 7-(1,2,3-Trihydroxy-1,2-O-isopropylidenepropyl)pteridines and Deoxygenation of Their 3’-Hydroxy Groups 355 365 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Daisuke Takayama Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 3,4-O-isopropylidene-L-threo-pentos-2-ulose (7) with 5,6-diamino-1,3-dimethyluracil (8) afforded 1,3-dimethyl-6-[(1R,2S)-1,2,3-trihydroxy-1,2-O-isopropylidenepropyl]lumazine (9a) and its 7-substituted isomer (9b). Deoxygenation of 3’-hydroxy groups of 9a,b was investigated in connection with a practical transformation of neopterin into biopterin. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 15 12 2025 Effectiveness of education programme to increase competency of health cadres in Indonesia: a cluster non-randomised controlled trial e095428 EN Dewie Sulistyorini Graduate School of Biomedical and Health Sciences, Hiroshima University K A T M Ehsanul Huq Graduate School of Biomedical and Health Sciences, Hiroshima University Abdulfatai Olamilekan Babaita Graduate School of Biomedical and Health Sciences, Hiroshima University Sadia A Aivey Graduate School of Biomedical and Health Sciences, Hiroshima University Gao Huiying Graduate School of Biomedical and Health Sciences, Hiroshima University Kana Kazawa Faculty of Health Sciences, Okayama University Yasuko Fukushima Graduate School of Biomedical and Health Sciences, Hiroshima University Mayumi Kako Graduate School of Biomedical and Health Sciences, Hiroshima University Michiko Moriyama Graduate School of Biomedical and Health Sciences, Hiroshima University Objectives Health cadres, who assist midwives in supporting pregnant women in community settings, need to enhance their competencies in identifying risk factors and referring high-risk pregnant women to midwives for further care. Since the capabilities of these health cadres are influenced by maternal complications, an educational programme was implemented to strengthen their skills. Therefore, this study aimed to evaluate the competency of health cadres by providing a researcher-developed educational programme. Design An open-label, cluster non-randomised controlled trial. Setting and participants Health cadres with at least 1 year of work experience were recruited at six public health centres (PHCs) in Banjarnegara Regency, Indonesia. Interventions Six PHCs were selected and allocated into intervention group (IG=3 PHCs) and control group (CG=3 PHCs) groups. A total of 133 female health cadres were enrolled across the selected PHCs. At each PHC, a systematic random sampling method was used to select the participants. The researchers and health professionals provided a 3-week period of theoretical and scenario-based simulations to the IG, while the CG received no education. Outcome measures Researcher-developed questionnaires and checklists were used to assess the knowledge, skills (health assessment, communication, attitude) and confidence. The primary endpoint was competency, a total score of knowledge and skills. The outcome domains were compared between the two groups, and a linear mixed-effect model was used to account for cluster-level variation. Results A total of 130 (97.7%) completed the study (IG:64, CG:66). The competency score showed significant improvement at endline (CG=49.5 and IG=52.5; p=0.002). The median scores for health assessment skills (CG=12 vs IG=14; p<0.001) and communication skills (CG=7 vs IG=8; p<0.001) were increased in the IG compared with the CG. Mixed-effect model indicated that groups (β (95% CI) 2.49 (0.57 to 4.41), p=0.012), baseline knowledge (β(95% CI) 0.73 (0.54 to 0.92), p<0.001) and midline health assessment skills (β (95% CI) 0.54 (0.25 to 0.82), p<0.001) were significant positive predictors, while age was negatively associated with competency (β (95% CI) －0.20 (－0.30 to －0.10), p<0.001)). Conclusion Education effectively increased the competency of health cadres. A well-structured education programme is necessary for health cadres to improve and maintain their competencies in monitoring high-risk pregnant women. Trial registration number NCT06134518. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-042X 16 2025 Activation of the pentose phosphate pathway by microcurrent stimulation mediates antioxidant effects in inflammation-stimulated macrophages 1666999 EN Mikiko Uemura Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Noriaki Maeshige Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Atomu Yamaguchi Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Xiaoqi Ma Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Yunfei Fu Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Taketo Inoue Assisted Reproductive Technology Center, Okayama University Mami Matsuda Graduate School of Science, Technology and Innovation, Kobe University Yuya Nishimura Graduate School of Science, Technology and Innovation, Kobe University Tomohisa Hasunuma Graduate School of Science, Technology and Innovation, Kobe University Ji Wang Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University Hiroyo Kondo Department of Nutrition, Faculty of Health and Nutrition, Shubun University Hidemi Fujino Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences Introduction: Excessive inflammatory responses in macrophages lead to increased oxidative stress, and the excessive production of reactive oxygen species (ROS) causes tissue damage, contributing to the development of chronic diseases and tissue deterioration. Therefore, controlling the inflammatory response and ROS production is crucial for human health. Electrical stimulation (ES) has been shown to have antioxidant and anti-inflammatory effects on macrophages. However, the key pathway underlying these effects remains unclear. Methods: In this study, ES was applied to Lipopolysaccharide (LPS)-stimulated macrophages, and the production of ROS and 8–hydroxy–2′–deoxyguanosine (8-OHdG), inflammatory cytokine expression, and intracellular metabolites were analyzed in a glucose-6-phosphate dehydrogenase (G6PD) knockdown experiment, the rate-limiting enzyme of the Pentose Phosphate Pathway(PPP). Results: ES significantly increased sedoheptulose 7-phosphate (S7P), an intermediate metabolite in PPP, and reduced ROS and 8-OHdG production and the expression of inflammatory cytokines in LPS-stimulated macrophages. Meanwhile, ES did not exert antioxidant effects in G6PD-knockdown macrophages. Discussion: These findings indicate that the antioxidant effects of ES are mediated by PPP in LPS-stimulated macrophages. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice 421 429 EN Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/69844 Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533±128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577±63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. No potential conflict of interest relevant to this article was reported.

British Editorial Society of Bone & Joint Surgery Acta Medica Okayama 2633-1462 6 8 2025 Long-term functional and quality of life outcomes after cementless minimally invasive extendable endoprosthesis replacement in skeletally immature patients with bone sarcomas at the lower limb a Japanese Musculoskeletal Oncology Group (JMOG) study 954 963 EN Yusuke Tsuda Department of Orthopaedic Surgery, The University of Tokyo Hospital Yoshihiro Nishida Department of Rehabilitation, Nagoya University Hospital Akio Sakamoto Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University Koichi Ogura Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Sekita Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Hirotaka Kawano Department of Orthopaedic Surgery, Teikyo University School of Medicine Hiroshi Kobayashi Department of Orthopaedic Surgery, The University of Tokyo Hospital Aims Extendable endoprostheses are utilized to reconstruct segmental defects following resection of bone sarcomas in skeletally immature children. However, there remains a paucity of data regarding long-term functional and quality of life outcomes. Methods We conducted a retrospective, multicentre study and reviewed 45 children who underwent cementless minimally invasive extendable endoprosthetic replacement. Anatomical sites included the distal femur (n = 29), proximal femur (n = 4), proximal tibia (n = 11), and total femur (n = 1). The mean follow-up period was 12 years. The mean age at extendable endoprosthetic replacement was ten years (5 to 15). Most patients (96%, 43/45) had reached skeletal maturity at the final follow-up. Results The ten-year endoprosthetic failure-free survival rate was 60%. Of the 45 patients, 25 (56%) had 42 complications which were frequently related to structural failure (45%, 19/42), with extension mechanism jamming being the most common (n = 7, 17%). Excluding lengthening procedures, 20 patients (44%) underwent additional surgery with a mean of two surgeries per patient. The mean limb-length discrepancy at the final follow-up was 2.3 cm. Limb salvage was achieved in 44 (98%) patients. The mean Musculoskeletal Tumor Society (MSTS) scores, Toronto Extremity Salvage Score (TESS), and EuroQol five-dimension five-level questionnaire (EQ-5D-5L) were 78%, 92%, and 92% at the last follow-up, respectively. Multiple additional surgeries (≥ 2 times) for complications were associated with worse MSTS scores compared with those without multiple additional surgeries (p = 0.009). Moreover, limb-length discrepancy > 3 cm showed significantly worse MSTS scores compared with those ≤ 3 cm (p = 0.019). Conclusion Extendable endoprostheses were associated with a high complication rate and need for additional surgeries over time, especially for structural-related complications. Despite this, successful limb salvage with reasonable function/quality of life and small limb-length discrepancy were achievable in the long term. Patients’ function in the long term depended on the experience of postoperative complications and limb-length discrepancy. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2304-6767 13 12 2025 Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model 577 EN Mohammad Nurhamim Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yixuan Zhang Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Momoko Nakahara Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Okayama University Hospital Yosei Nagashima Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The study aim was to investigate the effects of extracellular vesicles (EVs) derived miR-128-3p on renal inflammation using a rat periodontitis model. Methods: Ten-week-old male Wistar rats were divided into two groups: a control (n = 8) and a lipopolysaccharides (LPS) group (n = 8). The LPS group received LPS (Porphyromonas gingivalis) injection in the gingiva for 7 days. At the end of the experiment, plasma, gingival tissue, and kidney samples were collected. Hematoxylin and eosin staining was performed to evaluate the glomerular tissue injury score. Bioinformatic analysis was conducted to identify potential target genes of miR-128-3p. The reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-128-3p, inflammatory, pro-inflammatory cytokine, chemokine and predicting gene’s expression. The control and LPS groups were compared using Welch’s t-test. p-values < 0.05 were considered to indicate statistical significance. Results: The kidney glomerular tissue injury score was significantly higher in the LPS than in the control group. miR-128-3p expression in the LPS group was significantly higher in the gingival tissue and plasma. mRNAs (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, C-X3-C motif chemokine ligand 1 [CX3CL1], and C-X-C motif chemokine ligand 7 [CXCL7]) expression was higher in the kidney of the LPS group. The potential target genes of activin A receptor type I (Acvr1), ribosomal protein S6 kinase B1 (Rps6kb1), and transforming growth factor beta receptor type 1 (Tgfbr1) were significantly lower in the kidneys of the LPS group. Conclusions: EVs-derived miR-128-3p in LPS induced periodontitis may cause kidney inflammation which may be mediated by, Rps6kb1, Tgfbr1, and Acvr1. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2253 24 1 2024 Efficacy of Pericapsular Nerve Group (PENG) block in preoperative rehabilitation (Prehabilitation) for patients with femoral neck fractures: study protocol for a randomized, placebo-controlled, double-blinded trial 436 EN Zhuan Jin Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Sugiyama Department of Anesthesiology, Kameda Medical Center Fumiya Higo Department of Rehabilitation, Kameda Medical Center Takahiro Hirata Department of Rehabilitation, Kameda Medical Center Osamu Kobayashi Department of Anesthesiology, Kameda Medical Center Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenichi Ueda Department of Anesthesiology, Kameda Medical Center Background Despite surgery intervention for femoral neck fractures is recommended within 48 h of admission, achieving timely surgery presents challenges for patients with severe comorbidities, or in resource-limited settings. Preoperative rehabilitation (prehabilitation) reduces bedridden time, enhances mobility, and improves postoperative outcomes for patients scheduled for hip arthroplasty due to femoral neck fractures. However, prehabilitation is hindered by insufficient pain control. The pericapsular nerve group (PENG) block provides effective analgesia while preserving motor function. We designed a study to assess the efficacy of PENG block in facilitating prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. Methods This prospective randomized placebo-controlled double-blinded trial aims to enroll 100 patients with Garden 3 or 4 femoral neck fractures who are scheduled for hip arthroplasty. Participants will be randomly assigned to receive a PENG block with 0.375% ropivacaine (PENG group) or with normal saline (placebo group) before the initial prehabilitation session. The prehabilitation program comprises five items: Bed-sitting, Edge-sitting, Stand-up, Maintaining-standing, and Wheelchair-transfer, performed with the assistance of a single physical therapist. The primary outcome is the percentage of patients completing the entire prehabilitation program. Secondary outcomes during the initial prehabilitation session are the achievement of each program item and the Numerical Rating Scale (NRS) pain score. Other secondary outcomes include intraoperative bleeding amounts, thromboembolic events during postoperative day 0 to 7, postoperative 3-day cumulative Cumulated Ambulation Score (CAS), and discharge destination. The postoperative outcomes will be compared between subgroups of patients undergoing surgery within 48 h of admission and those undergoing surgery more than 48 h of admission. Discussion This is the first study aiming to assess the efficacy of PENG block in prehabilitation for patients with femoral neck fractures who are scheduled for hip arthroplasty. PENG block could be beneficial, especially for patients facing delayed surgery, providing a potential treatment option during the waiting period. Trial registration Japan Registry of Clinical Trials, jRCT1031220294, registered on August 26, 2022. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2328-9503 2025 INF2-Related Charcot–Marie–Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights EN Chikashi Yano Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Masahiro Ando Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yujiro Higuchi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Jun‐Hui Yuan Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Akiko Yoshimura Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Takahiro Hobara Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Risa Nagatomo Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Fumikazu Kojima Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yu Hiramatsu Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Satoshi Nozuma Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Tomonori Nakamura Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yusuke Sakiyama Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Chika Matsuoka Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Yamashita Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Kimura Department of Neurology, Hyogo Medical University Ayako Miyazaki Department of Clinical Genetics, Hyogo Medical University Chinatsu Kinjo Department of Clinical Genetics, Hyogo Medical University Kenji Yokochi Department of Pediatrics, Toyohashi Municipal Hospital Nanami Yamanaka Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine Nozomu Matsuda Department of Neurology, Fukushima Medical University School of Medicine Tomoki Suichi Department of Neurology, Graduate School of Medicine, Chiba University Yoshiyuki Hanaoka Department of Pediatrics, Kurashiki Central Hospital Haruka Kojima Department of Neurology, Tokyo Women's Medical University Kenichi Todo Department of Neurology, Tokyo Women's Medical University Hiroyuki Ishiura Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Mitsui Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo Shoji Tsuji Department of Neurology, The University of Tokyo Hospital Hiroshi Takashima Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Background: INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot–Marie–Tooth disease (CMT). Accurate genetic diagnosis is critical, as INF2-related FSGS is typically resistant to immunotherapy yet rarely recurs after transplantation, and its associated neuropathy can mimic treatable immune-mediated disorders such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: We performed a multicenter study investigating 3329 Japanese patients with inherited peripheral neuropathies/CMT who underwent gene panel sequencing or whole-exome analysis between 2007 and 2024. Clinical data, including electrophysiological assessments, were obtained from the patients' medical records. Results: We identified six pathogenic INF2 variants in eight patients, all of which were located within the diaphanous inhibitory domain. Structural modeling revealed clustering of variants near the diaphanous autoregulatory domain-binding pocket, which is critical for INF2 autoinhibition. Clinically, all cases were sporadic, with a median age at neurological onset of 9 years. All patients exhibited lower limb weakness, and 6/8 (75%) had sensory disturbances. All patients also developed kidney dysfunction, with 7/8 (88%) progressing to end-stage renal disease at a median age of 15 years. Furthermore, all patients showed demyelinating neuropathy, and 2/8 (25%) received immunotherapy due to suspected immune-mediated neuropathy. Conclusion: Although INF2 variants are a rare cause of CMT in Japan, they should be considered in pediatric patients with demyelinating neuropathy and early-onset proteinuria, even in the absence of a family history. Blood and urine tests assessing renal dysfunction can provide guidance for appropriate genetic testing. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0962-8819 34 1 2025 Highly efficient transgenesis mediated by Tip100 transposon system in medaka 46 EN Yoshitaka Tanaka Ushimado Marine Institute (UMI), Okayama University Takahide Seki Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University Atsushi Hoshino National Institute for Basic Biology Satoshi Ansai Ushimado Marine Institute (UMI), Okayama University Transgenesis mediated by transposon is an effective approach for introducing exogenous DNA into the nuclear genome and establishing stable transgenic strains that efficiently express genetic tools. Although the DNA transposon Tol2 is widely used for transgenesis in zebrafish, its endogenous transpositional activity can lead to unintended transgene mobilization, making it unsuitable for transgenesis in medaka (Oryzias latipes). Here, we demonstrated that the DNA transposon Tip100, originally identified in the common morning glory (Ipomoea purpurea), an ornamental plant, can serve as a useful tool for transgenesis in Japanese medaka. The GFP transgene cassette, when co-injected with Tip100 transposase mRNA, was expressed in significantly higher number of somatic cells in the injected fish. Furthermore, a transgene flanked by truncated recognition sequences (100 bp each) exhibited expression levels comparable to those of the original vector containing the full 2.2 kb recognition sequence. Injection of a transgene driven by a germline-specific promoter revealed that fish injected with Tip100 mRNA exhibited a significantly higher germline transmission rate (42/68; 62.7%) compared to those injected without the mRNA (13/62; 21.0%). We successfully established transgenic strains by outcrossing injected founders with GFP-positive germ cells (7/7; 100%) and demonstrated that the transgenes were randomly integrated into the medaka genome, generating 8-bp duplications at the insertional sites–an insertional signature of the hAT superfamily of transposons. Our findings indicate that the Tip100 system is a promising tool for generating stable transgenic strains that express various genetic tools in medaka and potentially other fish species. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Blood Pressure and Heart Rate Patterns Identified by Unsupervised Machine Learning and Their Associations with Subclinical Cerebral and Renal Damage in a Japanese Community: The Masuda Study 369 379 EN Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sosuke Munetomo Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mari Fukuda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuhide Kojima Department of Radiology, Okayama University Hospital Kaori Taniguchi Department of Environmental Medicine and Public Health, Izumo, Shimane University Faculty of Medicine Noriko Nakahata Department of Health and Nutrition, The University of Shimane Faculty of Nursing and Nutrition Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/69438 We applied unsupervised machine learning to analyze blood pressure (BP) and resting heart rate (HR) patterns measured during a 1-year period to assess their cross-sectional relationships with subclinical cerebral and renal target damage. Dimension reduction via uniform manifold approximation and projection, followed by K-means++ clustering, was used to categorize 362 community-dwelling participants (mean age, 56.2 years; 54.9% women) into three groups: Low BP and Low HR (Lo-BP/Lo-HR), High BP and High HR (Hi-BP/Hi-HR), and Low BP and High HR (Lo-BP/Hi-HR). Cerebral vessel lesions were defined as the presence of at least one of the following magnetic resonance imaging findings: lacunar infarcts, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. A high urinary albumin-to-creatinine ratio (UACR) was defined as the top 10% (≥ 12 mg/g) of the mean value from ≥2 measurements. Poisson regression with robust error variance, adjusted for demographics, lifestyle, and medical history, showed that the Hi-BP/Hi-HR group had relative risks of 3.62 (95% confidence interval, 1.75-7.46) for cerebral vessel lesions and 3.58 (1.33-9.67) for high UACR, and the Lo-BP/Hi-HR group had a relative risk of 3.09 (1.12-8.57) for high UACR, compared with the Lo-BP/Lo-HR group. These findings demonstrate the utility of an unsupervised, data-driven approach for identifying physiological patterns associated with subclinical target organ damage. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Evaluation of Scleral Adjustment Method: A Novel Adjustable Suture Technique in Strabismus Surgery 339 343 EN Ichiro Hamasaki Lino Eye Clinic Kiyo Shibata Lino Eye Clinic Original Article 10.18926/AMO/69434 To determine whether passing a pole suture through the sclera at two points provides fixation comparable to that of a sliding noose, we measured the tensile strength of the suture‒sclera interface during simulated traction. In this in vitro study, three suture patterns were evaluated in porcine eyeballs, using 6-0 polyglycolic acid sutures. Patterns A (control), B (second suture pass perpendicular), and C (second suture pass in the same direction) were compared. The tensile strength of each pattern was measured 20 times using a KANON TK300CN, and the results were analyzed using the Kruskal‒Wallis test. Pattern A showed a tensile strength of 2±4 gram-force (gf) (range: 0-12). Pattern B showed 112±38 gf (range: 61-184). Pattern C showed 139±31 gf (range: 97-204). Patterns B and C had significantly higher tensile strengths than Pattern A (p<0.001). Although Pattern C was not significantly different from Pattern B (p=0.363), it exhibited the highest tensile strength. Lifting the suture between the first and second suture passes allows for an adjustable suture length, suggesting that adjustability can be achieved using only the sclera. This scleral adjustment method with a second suture pass offers a durable means of securing extraocular muscles and may represent a valuable addition to adjustable suturing techniques. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 A Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery 321 328 EN Taisuke Obata Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Review 10.18926/AMO/69432 Bile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1328-8067 67 1 2025 Changes in body mass index during early childhood on school‐age asthma prevalence classified by phenotypes and sex e70090 EN Toshihiko Yabuuchi Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masanori Ikeda Department of Pediatrics, Okayama University Medical School Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Few studies have explored the relationship between changes in body mass index(BMI) during early childhood and asthma prevalence divided by phenotypes and sex, and the limited results are conflicting. This study assessed the impact of BMI changes during early childhood on school-age asthma, classified by phenotypes and sex, using a nationwide longitudinal survey in Japan. Methods: From children born in 2001 (n = 47,015), we divided participants into BMI quartiles (Q1, Q2, Q3, and Q4) and the following BMI categories: Q1Q1 (i.e., Q1 at birth and Q1 at age 7), Q1Q4, Q4Q1, Q4Q4, and others. Asthma history from ages 7 to 8 was analyzed, with bronchial asthma (BA) further categorized as allergic asthma (AA) or nonallergic asthma (NA) based on the presence of other allergic diseases. Using logistic regression, we estimated the asthma odds ratio (OR) and 95% confidence intervals (CIs) for each BMI category. Results: Q1Q4 showed significantly higher risks of BA, AA, and NA. In boys, BA and NA risks were significantly higher in Q1Q4 (adjusted OR: 1.47 [95% CI: 1.17–1.85], at 1.56 [95% CI: 1.16–2.1]), with no significant difference in AA risk. In girls, no increased asthma risk was observed in Q1Q4, but AA risk was significantly higher in Q4Q4 (adjusted OR: 1.78 [95% CI: 1.21–2.6]). Conclusion: Our results demonstrated that BMI changes during early childhood impact asthma risks, particularly that the risk of NA in boys increases with BMI changes during early childhood, and the risk of AA in girls increases with consistently high BMI. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-230X 25 1 2025 A study on the timing of small-bowel capsule endoscopy and its impact on the detection rate of bleeding sources 434 EN Daisuke Kametaka Division of Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Small-bowel capsule endoscopy (SBCE) is an essential diagnostic tool for obscure gastrointestinal bleeding, particularly for identifying bleeding sources in the small intestine. The timing of SBCE is thought to affect its diagnostic yield; however, the optimal timing remains unknown. Methods This retrospective study analyzed 131 patients with overt gastrointestinal bleeding managed with SBCE at our institution between May 2015 and December 2022. Patients were categorized into four groups based on the interval between their last bleeding episode and SBCE: 1–7, 8–14, 15–28, and ≥ 29 days. Results Positive findings were observed in approximately 50% of the cases across all intervals, with no statistically significant differences in the detection rates. Vascular lesions were detected primarily within 1–14 days, whereas inflammatory lesions, tumors, and diverticula were identified across all intervals. Notably, 25% of the patients with negative SBCE findings were later diagnosed with sources of non-small bowel bleeding, highlighting the value of follow-up endoscopic evaluations. Conclusions Our findings suggest that SBCE can be effective regardless of the time after a bleeding event, contrary to previous recommendations emphasizing its early use. Clinicians should consider performing SBCE whenever feasible to improve the diagnostic outcomes for gastrointestinal bleeding, irrespective of the elapsed time since the last episode. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0020-7292 2025 Determinants of residual myometrial thickness after cesarean delivery: Comparative analysis of barbed versus conventional sutures―A sub‐analysis from the SPIRAL trial EN Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikaru Ooba Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Mitoma Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayano Suemori Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Kuriyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shujiro Sakata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: This sub-analysis aimed to determine whether conventional suture-associated risk factors for cesarean scar defect show similar outcomes with barbed continuous suturing, and to identify factors influencing residual myometrial thickness when using barbed continuous sutures. Methods: This sub-analysis of a multicenter, parallel-group, randomized controlled trial across four Japanese obstetrics and gynecology departments included 1211 women who had their first cesarean delivery between May 2020 and March 2023. Among them, 298 women underwent a C-section, with 253 follow-up through July 2023. Singleton pregnancies were randomly assigned to receive either barbed or conventional double-layered continuous sutures in a 1:1 ratio; they were monitored from consent through their 6- to 7-month check-up. The effects of cervical ripening, facility characteristics, and surgeon experience were investigated using a two-way ANOVA. Results: Of the remaining 253 patients, 33 were lost to follow-up and 220 completed follow-up (110 per group). One institution enrolled the largest proportion of participants (45.9%), whereas two other institutions had more experienced surgeons. Two-way ANOVA revealed that surgeon experience (P = 0.020) and institutional factors (P < 0.001) significantly influenced the residual myometrial thickness at 6–7 months after surgery, whereas cervical dilation during active labor did not (P = 0.215). Additionally, a significant interaction was observed between institutional factors and suture type (barbed vs. conventional) on residual myometrial thickness (Pinteraction <0.001). Conclusion: Institutional factors and surgeon experience represent significant determinants of residual myometrial thickness when using barbed sutures for cesarean closure, highlighting the importance of standardized surgical protocols and training across facilities. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2458 25 1 2025 Longitudinal changes and tracking of in-school physical activity in primary school children: four-year longitudinal study 1041 EN Kensaku Sasayama Faculty of Education, Mie University Jin Yasunebe Faculty of Education, Okayama University Minoru Adachi Graduate School of Education, Okayama University Background There is little evidence on the tracking of physical activity during school hours. In addition, tracking physical activity in schools provides important evidence for understanding children’s physical activity and conducting intervention studies. Therefore, this study examined longitudinal changes and tracking of in-school physical activity in primary school children. Methods In this study, physical activity was investigated longitudinally in primary school children for 4 years. The baseline participants consisted of 103 second-grade students (7–8 years old) who participated. Step counts and moderate-to-vigorous physical activity (MVPA) in school and during first recess and lunch/second recess were examined using an accelerometer (Kenz Lifecorder GS 4-second version; Suzuken Co. Ltd, Nagoya, Japan). Results After excluding missing data (moving school; n = 8, physical activity; n = 8), 87 (43 boys and 44 girls) of whom were included in the final analysis. Step counts and MVPA during school and physical education in boys did not decrease across the school years. By contrast, in girls, step counts during school did not decrease across the school years, however MVPA did decrease. In addition, for both sexes, step counts and MVPA during first recess decrease across the school years. During lunch/second recess, only step counts decrease across the school years in both sexes. In addition, the tracking coefficients for step counts and MVPA for boys in school and during first recess and lunch/second recess were found across many school years. Contrarily, girls had fewer significant tracking coefficients between school years than boys. There were also few significant tracking coefficients between grades for physical education step counts and MVPA for both boys and girls. Conclusions Our results suggested that in-school step counts for both boys and girls does not decrease across the school years. However, given that girls demonstrated reduced levels of in-school MVPA across the school years, it is important to promote strategies to increase MVPA in this group. No potential conflict of interest relevant to this article was reported.

African Journals Online (AJOL) Acta Medica Okayama 1726-801X 39 8 2025 Chemical composition of essential oil of Acacia crassicarpa Benth. (Fabaceae) from Vietnam 1653 1660 EN Tuan Quoc Doan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tai Tien Dinh Hue Union of Science and Technology Associations (HUSTA) Tetsuya K. Matsumoto Graduate School of Science and Engineering, Ibaraki University Dien Dinh Phong Dien Nature Reserve, Phong Dien district, Thua Thien Hue province Naoko Miki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Muneto Hirobe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hoai Thi Nguyen Faculty of Pharmacy, Hue University of Medicine and Pharmacy, Hue University This research aimed to identify the volatile compounds found in the fresh leaves of Acacia crassicarpa Benth. This is the first phytochemical investigation of this species. Essential oils from the leaves of A. crassicarpa were obtained by hydro-distillation and analyzed by gas chromatography coupled with mass spectrometry (GC/MS). Sixty-one compounds accounting for 95.8% of the leaf oil were identified. The classes of compounds identified in the oil sample were aldehydes (30.7%), sesquiterpene hydrocarbons (25.2%), alkanes (19.1%), oxygenated monoterpenes (3.6%) oxygenated sesquiterpenes (2.3%), monoterpene hydrocarbons (0.8%) and others (14.2%). The major constituents in the leaf oil were tridecanal (24.5%), (E)-caryophyllene (11.7%), n-heneicosane (7.2%), squalene (6.5%), and 7-tetradecenal (5.9%). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling EN Yuto NAOI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 An Asymptomatic Perigraft Seroma in a Patient who Underwent Aortic Root Replacement for Annulo-Aortic Ectasia 205 208 EN Yasufumi Fujita Department of Cardiovascular Surgery, Kure Kyosai Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/68728 Perigraft seroma, a sterile fluid accumulation around the graft, is a potential complication after thoracic aortic surgery. The optimal treatment strategy for a perigraft seroma with vascular compression after thoracic aortic surgery has been unclear. We describe the case of a 62-year-old Japanese male in whom an asymptomatic perigraft seroma was observed after he had undergone aortic root replacement for annulo-aortic ectasia. The seroma was successfully treated with thoracoscopic drainage and conservative therapy. Less invasive therapy, including conservative therapy, may also be an option for asymptomatic perigraft seromas observed after thoracic aortic surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 3 2025 Immunometabolic Regulation of Innate Immunity in Systemic Lupus Erythematosus 147 155 EN Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/68722 Pathogens or their components can induce long-lasting changes in the behavior of innate immune cells, a process analogous to “training” for future threats or environmental adaptation. However, such training can sometimes have unintended consequences, such as the development of autoimmunity. Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease characterized by the production of autoantibodies and progressive organ damage. Innate immunity plays a central role in its pathogenesis, contributing through impaired clearance of apoptotic cells, excessive type I interferon production, and dysregulated formation of neutrophil extracellular traps. Recent studies have revealed that metabolites and nucleic acids derived from mitochondria, a crucial energy production site, directly regulate type I interferon and anti-inflammatory cytokine production. These insights have fueled interest in targeting metabolic pathways as a novel therapeutic approach for SLE, offering promise for improving long-term patient outcomes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 7 2025 Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis 2287 EN Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP. No potential conflict of interest relevant to this article was reported.

岡山大学教育学部 Acta Medica Okayama 0471-4008 111 1999 メルボルンにおけるインドネシア移民 75 85 EN Masao NOBE Department of Social Studies Education, Faculty of Education, Okayama University 10.18926/bgeou/68558 　本稿では，参与観察によってメルボルンに住むインドネシア人の生活を解明した。明らかになったのは，次の9点である。(1)インドネシア人はメルボルンの中で分散して住んでいる。(2)インドネシア人の教会は親睦集団としての性格が強い。社会階層による対立が教会のメンバーの中に見られる。(3)メルボルンに住むインドネシア人は宗教によって分断されている。(4)夫婦共働きの増加と自家用車の普及によって，近隣関係がだんだんと希薄になっている。(5)窃盗の増加に対抗するため，住民は「ネイバーフッド・ウォッチ」という防犯のための相互協力組織を結成した。しかし，その活動はあまり活発でない。(6)参与観察をしたインドネシア移民の女性は，近隣地域であまり社会関係を持っておらず，メルボルンのさまざまな場所で友人関係を組織していた。また，大部分の友人関係はインドネシア人と取り結んでいた。(7)インドネシア移民の子供は家庭と学校のしつけが異なるから，混乱をしてしまう。(8)インドネシア移民は日常生活で差別されていると感じている。(9)移民のオーストラリアでの職業的地位はたいてい本国でのそれよりも低い。 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Endothelial Cell Polarity in Health and Disease 1 7 EN Moe Thiha Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hikita Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Nakayama Department of Pathophysiology and Drug Discovery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/68353 Endothelial cell polarity is fundamental to the organization and function of blood vessels, influencing processes such as angiogenesis, vascular stability, and response to shear stress. This review elaborates on the molecular mechanisms that regulate endothelial cell polarity, focusing on key players like the PAR polarity complex and Rho family GTPases. These pathways coordinate the front–rear, apical–basal and planar polarity of endothelial cells, which are essential for the proper formation and maintenance of vascular structures. In health, endothelial polarity ensures not only the orderly development of blood vessels, with tip cells adopting distinct polarities during angiogenesis, but also ensures proper vascular integrity and function. In disease states, however, disruptions in polarity contribute to pathologies such as coronary artery disease, where altered planar polarity exacerbates atherosclerosis, and cancer, where disrupted polarity in tumor vasculature leads to abnormal vessel growth and function. Understanding cell polarity and its disruption is fundamental not only to comprehending how cells interact with their microenvironment and organize themselves into complex, organ-specific tissues but also to developing novel, targeted, and therapeutic strategies for a range of diseases, from cardiovascular disorders to malignancies, ultimately improving patient outcomes. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1751-0759 18 1 2024 Psychogenic fever and neurodevelopmental disorders among Japanese children 23 EN Ayumi Okada Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshie Shigeyasu Department of Pediatrics, Okayama University Hospital Chikako Fujii Department of Pediatrics, Okayama University Hospital Chie Tanaka Department of Pediatrics, Okayama University Hospital Mana Hanzawa Department of Pediatrics, Okayama University Hospital Akiko Sugihara Department of Pediatrics, Okayama University Hospital Makiko Horiuchi Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Psychosocial stress can induce various physical symptoms, including fever, which is a commonly seen symptom in pediatric practice. In cases of unexplained fever, psychogenic fever should be considered as a potential cause. Children with neurodevelopmental disorders may be more vulnerable to stress and therefore more prone to developing somatic symptoms than their peers. This study aimed to elucidate the characteristics of children with psychogenic fever and comorbidity. Methods This study included 21 patients with psychogenic fever who visited the Department of Pediatric Psychosomatic Medicine, Okayama University Hospital. Information on age, sex, disease onset, final estimated diagnosis, comorbidities, treatment course, and outcome was obtained from the patients' medical records. Results Of the 21 patients included, 7 were boys and 14 were girls, and their median age was 13.0 (range: 8.6-14.6) years. A total of 19 patients had no attendance at school, and all patients showed signs of maladjustment in school. The comorbidities included orthostatic dysregulation (n = 4) and migraine (n = 3). Neurodevelopmental disorders were observed in nine patients, eight of whom were diagnosed after the initial visit. The mean treatment duration was 37.2 months. The outcomes were complete remission (n = 9), improvement (n = 4), discontinuation (n = 1), and referral to another physician (n = 7). Conclusion Various comorbidities were observed in the patients of this study with psychogenic fever, including the coexistence of neurodevelopmental disorders, such as autistic spectrum disorder. Children with neurodevelopmental disorders are prone to psychological stress resulting from difficulties in social adjustment. It is crucial to understand the developmental characteristics and environmental adaptation of patients to facilitate accurate diagnosis and treatment. No potential conflict of interest relevant to this article was reported.

Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 63 21 2024 Endoscopic and Histological Gastritis in University Students with Helicobacter pylori Infection 2875 2884 EN Shotaro Okanoue Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Sakae Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Yokota Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Obayashi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Abe Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective Although the characteristics of Helicobacter pylori infection have been extensively reported, there is a lack of consensus regarding its characteristics in young adults. The present study examined the endoscopic and histological characteristics of young adults who underwent eradication therapy for H. pylori infection. Methods We examined the H. pylori infection status of first-year students at Okayama University School of Medicine and Dentistry between 2014 and 2020. A total of 152 (6.8%) students who were positive for H. pylori antibody or pepsinogen tests were enrolled in the study. Among them, 107 students underwent endoscopy, and their biopsy samples were investigated. Seventy-five students were diagnosed with H. pylori infections. Results Of 75 H. pylori-positive patients, 57 (76.0%) had endoscopic atrophic gastritis, and 42 (56.0%) had histological atrophy. A few patients had severe atrophic gastritis. All 65 patients who underwent an eradication assessment were successfully treated. After successful eradication, 26 patients underwent endoscopic follow-up. The mean follow-up period was 32.9 months. A histological evaluation revealed that gastric antrum atrophy had subsided in 11 of 14 patients, and atrophy in the lesser curvature of the gastric body had subsided in 7 of 8 patients. Conclusion More than half of young adults with H. pylori infection had atrophic gastritis. We found mild atrophy in young adults, which subsided shortly after eradication treatment. This study provides a foundation for future studies to evaluate the validity of eradication therapy in preventing gastric cancer in patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Closure of Ventricular Septal Rupture through a Left Thoracotomy in a Patient with a History of Esophageal Reconstruction 449 452 EN Gentaro Kato Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Tatsuya Ogawa Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Tomohiro Hayashida Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shu Yamamoto Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Takeshi Shichijo Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital Case Report 10.18926/AMO/67870 A 73-year-old man who had undergone esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 8 years prior was transferred to our hospital for the treatment of an acute myocardial infarction. Emergent percutaneous coronary intervention for the left anterior descending artery (#7) was successfully performed. However, echocardiography revealed a ventricular septal rupture (25×27 mm). Seventeen days after admission, the rupture was successfully treated with a double-patch closure via a left anterolateral thoracotomy to avoid a surgical injury to his retrosternal gastric tube. Determining the best surgical approach to the heart is important for safe cardiac surgery in patients after esophageal reconstruction. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 68 6 2024 Relationships among eye dimensions in magnetic resonance images by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia 641 650 EN Reika Kono Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ichiro Hamasaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Fumiko Kishimoto Division of Ophthalmology, Ibara City Hospital Takehiro Shimizu Division of Ophthalmology, Okayama City Hospital Hiroya Kindo Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiyo Shibata Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shin Morisawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose To investigate the relationships among eye dimensions in magnetic resonance imaging (MRI) scans by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia. Study design Retrospective clinical case series. Methods We included 58 eyes of 29 patients with acquired strabismus and high myopia (mean age ± standard deviation: 60.2 ± 14.7 years, axial length [AL]: 28.69 ± 2.12 mm). For all eyes, the equatorial diameter of the globe/AL ratio (EAR) and the globe/orbit volume ratio (GOR) were measured using MRI. EAR and GOR values were compared between the following groups: 9 men vs. 20 women; 8 younger (< 56 years) vs. 21 older (≥ 56 years) patients; and non-esotropia strabismus (NES: 7 patients) vs. esotropia (ET: 13 patients) vs. restrictive strabismus (RS: 9 patients) groups. Results Female patients had a smaller EAR (0.87 ± 0.07) and larger GOR (0.38 ± 0.04) than male patients (0.92 ± 0.05 and 0.35 ± 0.03, both P < 0.01). Older patients had a smaller EAR (0.87 ± 0.07) than younger ones (0.93 ± 0.04, P < 0.01), without significant differences in GOR. EAR (NES: 0.92 ± 0.06, ET: 0.86 ± 0.06, RS: 0.89 ± 0.09) significantly differed among the three strabismus groups (P = 0.02: post-hoc test: NES vs. ET, P = 0.02; NES vs. RS, P = 0.49; RS vs. ET, P = 0.67), but no significant differences in GOR were found (P = 0.12). Conclusions Among patients with acquired strabismus and high myopia, women, older patients, and those with esotropia exhibit a smaller EAR and longer sphere shape with AL as the major axis. The parameter EAR might be useful for evaluating the pathogenesis of strabismus associated with high myopia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 The First Report of Bickerstaff Brainstem Encephalitis Induced by Atezolizumab for Metastatic Breast Cancer 407 412 EN Kyoko Shimoyama Department of Breast Surgery, Takatsuki General Hospital Atsushi Nakajima Department of Rehabilitation, Aijinkai Rehabilitation Hospital Yoshimitsu Minari Department of Breast Surgery, Takatsuki General Hospital Case Report 10.18926/AMO/67665 Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they have been known to cause immune-related adverse events (irAEs) by promoting T-cell activation. Neurological irAEs are rare (1%) but have a high fatality rate (11.5%). Here we report the first case of Bickerstaff brainstem encephalitis (BBE) induced by an ICI. A woman in her 60s with metastatic breast cancer was treated with atezolizumab plus nab-paclitaxel once intravenously. Eighteen days later, she lost consciousness with ophthalmoplegia and was diagnosed with a neurological irAE. She recovered consciousness immediately with the administration of intravenous immunoglobulin (IVIG) but suffered severe permanent peripheral neuropathy. Although it is just one case, this experience shows that BBE occurring as a neurological irAE of ICI cancer treatment may be associated with more severe outcomes than conventional BBE in metastatic cancer. Creating a system for multidisciplinary treatment is essential for ICI therapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Middle-Ear Salivary Gland Choristoma with Congenital, Single-Sided Hearing Loss 349 355 EN Yuichiro Tominaga Department of Otolaryngology, Head and Neck Surgery, Hiroshima City, Hiroshima Citizens Hospital Akiko Sugaya Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology, Head and Neck Surgery, Kawasaki Medical School Hospital Aiko Shimizu Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Kataoka Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/67554 Middle-ear salivary gland choristoma (SGCh) is a rare, benign tumor that causes conductive hearing loss owing to middle-ear morphological abnormalities. Early diagnosis is challenging, and surgical resection is indispensable for a definitive diagnosis. We report the case of a 3-year-old boy diagnosed with middle-ear SGCh during the follow-up period for left-sided hearing loss discovered at newborn hearing screening (NHS). Long-term follow-up after the NHS result, subsequent computed tomography/magnetic resonance imaging, and surgical resection led to its relatively early diagnosis and treatment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Multicenter Remote-Access Simulation of Vaginal Delivery for High-Flexibility Medical Education during the Coronavirus Pandemic 313 322 EN Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Yamashita Center for Education in Medicine and Health Sciences, Okayama University Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayano Suemori Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikari Nakato Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikaru Oba Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Mitoma Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoe Kirino Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Ohira Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/67547 During the coronavirus pandemic, face-to-face simulation education became impossible. Therefore, we aimed to develop remote-access simulation education with a sense of realism through Information and Communication Technology (ICT) using a perinatal whole-body management and delivery simulator. In September 2021, we administered a multi-center simultaneous remote simulation based on our developed model. Ten universities in the Chugoku–Shikoku region were connected via a web-conferencing system to a live broadcast of a virtual vaginal birth in which a fictional hospitalized pregnant woman experienced accelerated labor and gave birth through vacuum delivery for fetal distress. A Video on Demand (VOD) was made beforehand using a new simulator that allowed for a visual understanding of the process of the inter-vaginal examination. We provided a participatory program that enhanced the sense of realism by combining VOD and real-time lectures on each scenario, with two-way communication between participants and trainee doctors using a chat function. Most participants answered “satisfied” or “very satisfied” with the content, level of difficulty, and level of understanding. From November 2021, we have used the videos of all processes in face-to-face classes. Our construction of a high-flexibility education system using remote simulation in the field of obstetrics and gynecology, especially in the vaginal delivery module, is unique, creative, and sustainable. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 2473-4039 8 8 2024 Macrophages modulate mesenchymal stem cell function via tumor necrosis factor alpha in tooth extraction model ziae085 EN Aung Ye Mun Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Akiyama Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jiewen Zhang Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Wakana Kitagawa Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teisaku Kohno Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuji Tagashira Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Ishibashi Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoya Matsunaga Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tingling Zou Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuaki Ono Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction (n = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80+M1, CD206+M2 (anti-inflammatory macrophages), PDGFRα+MSC, and TNF-α+ cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm3 vs 0.02 mm3, p<.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p<.0001). Clodronate group showed significant reduction in mean number of CD80+, TNF-α+, PDGFRα+, and CD80+TNF-α+ cells on day 5 (306.5 vs 558.8, p<.0001; 280.5 vs 543.8, p<.0001; 365.0 vs 633.0, p<.0001, 29.0 vs 42.5, p<.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p=.0004; 479.3 vs 384.5, p=.0008; 593.0 vs 473.0, p=.0010, 41.0 vs 32.5, p=.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC’s immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e, Gbp6, and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2397-9070 8 7 2024 Rare case of rectal carcinoid with synchronous primary carcinoid tumors of the lung misdiagnosed as lung metastases e70003 EN Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School Rhohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School A 68-year-old woman was referred to our hospital for rectal surgery after a pathological diagnosis of rectal carcinoid with venous invasion following endoscopic submucosal dissection of a 5 mm-sized submucosal tumor in the lower rectum. Chest CT showed nodules in the left upper lobe and right lower lobe, but positron emission tomography and somatostatin receptor scintigraphy showed no hyperaccumulation in the lung nodules. CT-guided needle biopsy was performed on the nodular lesion in the left upper lobe, which showed focal growth of tumor cells with a high N/C ratio and positive synaptophysin, leading to a diagnosis of pulmonary metastasis of rectal carcinoid. Since the patient was asymptomatic and did not wish to undergo surgery or chemotherapy, she was followed up strictly with sufficient informed consent. Three years have passed since the diagnosis, and there is no tendency for the lung metastasis to increase, and no other new lesions have been observed. The disease had not progressed and remained stable. Therefore, immunohistological analysis of the lung biopsy specimen was performed again, which was positive for TTF-1 and negative for CDX2. Consequently, the diagnosis was changed to primary lung carcinoid tumors, and the patient remains under follow-up with no disease progression. No potential conflict of interest relevant to this article was reported.

International Institute of Anticancer Research Acta Medica Okayama 0250-7005 44 6 2024 Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8–mediated Crosstalk 2497 2509 EN YUNCHENG LI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROSHI TAZAWA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YASUO NAGAI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUTO FUJITA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOMOHIRO OKURA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences RYOHEI SHOJI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MOTOHIKO YAMADA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SATORU KIKUCHI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHINJI KURODA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIAKI OHARA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUHIRO NOMA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MASAHIKO NISHIZAKI Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUNSUKE KAGAWA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α–smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor–β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8–mediated crosstalk. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Impact of Light Touch and Pin Prick on Functional Outcomes in Patients with Traumatic Spinal Cord Injury 163 170 EN Takayuki Deguchi Department of Rehabilitation, Kagawa Rosai Hospital Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Kazunari Furusawa Department of Rehabilitation Medicine, Kibikogen Rehabilitation Center for Employment Injuries Nlandu Roger Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/66925 A spinal cord injury (SCI) can cause severe lifelong functional disability and profoundly affect an individual’s daily life. We investigated the prediction of patients’ post-SCI functional outcomes by evaluating sensory scores rather than motor scores, as the latter’s association with functional outcomes is well established. We examined patients’ responses to a light touch (LT) and pin prick (PP) at admission and the response data’s usefulness as predictors of functional outcomes (i.e., ability to perform activities of daily living) at discharge. This exploratory observational study used data from the Japanese National Spinal Cord Injury Database (SCI-J). Data from 3,676 patients who met the inclusion criteria and were admitted for an SCI between 1997 and 2020 were analyzed. The motor score of the Functional Independence Measure (mFIM) at discharge was used as an index of functional outcome. A multiple regression analysis revealed that the mFIM was associated with both the LT response (β=0.07 (0.01), p<0.001) and the PP response (β=0.07 (0.01), p<0.001) at admission. The false discovery rate log-worth values for LT and PP were 6.6 and 8.5, respectively. Our findings demonstrate that LT and PP scores at admission can help predict patients’ functional outcomes after an SCI, although the magnitude of their contributions is not high. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression 151 161 EN Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Mochizuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66924 Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 16 7 2024 Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation 1298 EN Kumiko Ohsawa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuka Gion Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences Keisuke Sawada Department of Pathology, Saitama Medical Center, Saitama Medical University Morihiro Higashi Department of Pathology, Saitama Medical Center, Saitama Medical University Michihide Tokuhira Department of Hematology, Japan Community Health Care Organization Saitama Medical Center Jun-Ichi Tamaru Department of Pathology, Saitama Medical Center, Saitama Medical University Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response 95 106 EN Junko Itano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/66912 The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Ectopic Breast Cancer Arising within an Axillary Lymph Node 89 93 EN Kei Toshima Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Midori Filiz Nishimura Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Case Report 10.18926/AMO/66676 We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma 63 70 EN Daizo Murakami Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Kohei Nishimoto Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Miyamaru Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Tomoka Kadowaki Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Saito Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Hiroki Takeda Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Momoko Ise Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Koichi Suyama Department of Medical Oncology, Toranomon Hospital Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine Original Article 10.18926/AMO/66672 The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Assessing the Frequency and Effectiveness of Various Arthroscopic Treatments in the Management of Symptomatic Isolated Medial Meniscus Injuries Including Medial Meniscus Posterior Root Tear: A Retrospective Observational Cohort Study 21 27 EN Masanori Tamura Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Furumatsu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yokoyama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kintaka Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naohiro Higashihara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koki Kawada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66667 The use of various strategies for arthroscopic meniscal repairs to save the meniscus and prevent the progression of knee osteoarthritis has gradually increased. We investigated the frequency of various arthroscopic treatments and the short-term clinical outcomes of symptomatic isolated medial meniscus (MM) injuries. This retrospective observational study included 193 patients (197 knees) who underwent arthroscopic meniscal treatment for isolated MM injuries between January 2016 and April 2019. Arthroscopic meniscal repairs were divided into two groups: transtibial pullout repairs of MM posterior root tears (MMPRTs) and arthroscopic meniscal repairs for other types of MM injuries. MMPRT pullout repair, other meniscal repairs, and partial meniscectomy were performed in 71.0%, 16.8%, and 12.2% of the knees, respectively. The ratio of women to men and the patient age were higher in the pullout-repair group than the meniscal-repair group. The Preoperative Knee Injury and Osteoarthritis Outcome Score subscale (as an index of daily living activities) was significantly lower in the pullout-repair group than the meniscus-repair group. However, no significant differences were observed in these scores among the two groups postoperatively. Our results suggest that familiarity with the diagnosis and treatment of MMPRTs is necessary for orthopedic surgeons to manage isolated MM injuries. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06) 15 20 EN Reina Maeda Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Mina Takahashi Department of Breast Oncology, NHO Shikoku Cancer Center Kengo Kawada Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Yukiko Kajiwara Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Shinichiro Kubo Department of Breast and Thyroid Surgery, Fukuyama City Hospital Daisuke Takabatake Department of Breast Surgery, Kochi Health Sciences Center Shoichiro Ohtani Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital Kinya Matsuoka Department of Breast and Thyroid Surgery, Ehime Prefectural Central Hospital Hajime Hikino Department of Breast Surgery, Matsue Red Cross Hospital Yutaka Ogasawara Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital Naruto Taira Department of Breast and Thyroid Surgery, Kawasaki Medical School Shozo Osumi Department of Breast Oncology, NHO Shikoku Cancer Center Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/66666 While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Role of Macrophages in Liver Fibrosis 1 8 EN Cuiming Sun Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/66664 Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 113 2024 Analytical studies on high-yielding characteristics of US soybean cv. ‘UA4805’ in comparison with Japanese cv. ‘Akimaro’ 25 32 EN Sultanzada Mohammad Marouf Graduate School of Environmental and Life Science Yu Hasegawa School of Agriculture Ryuta Manabe School of Agriculture Kuniyuki Saitoh Graduate School of Environmental and Life Science Field experiments were conducted in 2020 and 2021 at the Field Science Center of Okayama Univ. (34°41’ N, 133°55’ E). Two Soybean cultivars ‘UA4805’ and ‘Akimaro’ were sown with two planting densities, 12.5plants m－2 (sparse, 80×10cm) and 25plants m－2 (dense, 80×5cm)on May 25 (early), June 29 (normal), and Aug. 3 (late) in 2020, and 80 and 30cm row-width, and 12.5 and 25 plant m－2 in 2021 on June 23. Seed yield was higher in ‘UA4805’ than in ‘Akimaro’ in 2020 and 2021. The later the sowing time, the higher the seeds/stem ratio. Both cultivars showed higher dry matter in dense planting. Dry matter was higher in ‘Akimaro’, while seed yield was lower than ‘UA4805’. In contrast, ‘UA4805’ showed lower dry matter with higher seed yield. The numbers of nodes, pods, and seeds were higher in ‘UA4805’ resulting in the higher seed yield. Lodging score is larger in ‘Akimaro’ especially in dense planting. The seeds/stem ratio is much higher in ‘UA4805’ than ‘Akimaro’ across 2 densities, 3 sowing times and 2 row width. Pods setting ratio was nearly two times higher in ‘UA4805’ compared to ‘Akimaro’. The greater seed yield of ‘UA4805’ compared to ‘Akimaro’ was due to the higher pod setting ratio, seeds/stem ratio, and lower lodging score, nevertheless the dry matter was larger in ‘Akimaro’. If late sowing is applied, higher planting density is recommended for better seed yield. Narrow row is an effective way to improve seed yield in soybean. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 113 2024 水稲NERICA品種の農業形質に関する遺伝的要因 11 16 EN Asami Tomita Course of Applied Plant Science Yui Akimoto Course of Applied Plant Science Genetic factors of yield related traits in lowland New Rice for Africa variety (NERICA) using different nitrogen condition and QTL to increase rice yield in lowland NERICAs were clarified. Indica Group rice variety (Oryza sativa L.) IR64 increased panicle number, culm weight and panicle weight, according to nitrogen concentration. The tendency is especially remarkable under low nitrogen concentration. NERICA‒L‒19, which is derived from a cross between IR64 and TOG5681 (Oryza glaberrima S.), showed similar values for panicle weight and culm weight, and it showed higher plant height, panicle weight and culm weight and lower harvest index than those of IR64 under all the concentrations. QTL analysis for the agronomic traits were performed using hybrid population derived from a cross between IR64 and NERICA‒L‒19. A total of 22 QTLs were detected on chromosomes (chrs.) 1 (3 QTLs), 2 (2), 4 (2), 5 (5), 6 (1), 7 (1), 8 (6) and 10 (2). Among them, 4 regions at 34.1‒36.6Mbp of chr. 1, at 23.8‒27.8Mbp of chr. 5 and at 4.8Mbp and 20.3‒28.4Mbp of chr. 8 showed several QTLs’ peaks overlapped. The regions of chr. 5 and 4.8Mbp of chr. 8 increased panicle weight by IR64 allele. Those of chr. 1 and 20.3-28.4Mbp of chr. 8 increased plant height and harvest index, respectively, by NERICA‒L‒19 allele. These results indicated that the larger panicle type of lowland NERICA is suitable under low nitrogen condition. Also, the plant type was controlled by the combination of 4 QTLs’ regions on chr. 1 and short arm of chr. 8 originated from O. glaberrima, and those of chr. 5 and long arm of chr. 8 from O. sativa Indica Group. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0003-2670 1278 2023 Determination of mass-dependent chromium isotopic compositions in geological samples by double spike-total evaporation-thermal ionization mass spectrometry (DS-TE-TIMS) 341723 EN Dilan M. Ratnayake The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Background: 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. 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. 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.

Elsevier Acta Medica Okayama 1751-7311 17 7 2023 Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves 100873 EN S. Katsumata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Y. Hayashi Shiga Prefectural Livestock Production Technology Promotion Center K. Oishi Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University T. Tsukahara Kyoto Institute of Nutrition and Pathology R. Inoue Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University A. Obata Shiga Prefectural Livestock Production Technology Promotion Center H. Hirooka Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University H. Kumagai Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University Liquefied 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.

Society for Reproduction and Development Acta Medica Okayama 0916-8818 69 6 2023 Effects of insulin-like growth factor-1 on the mRNA expression of estradiol receptors, steroidogenic enzymes, and steroid production in bovine follicles 337 346 EN Ahmad Farid Rawan Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hikmatullah Langar Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Maho Munetomo Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuki Yamamoto Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kohei Kawano Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Koji Kimura Laboratory of Reproductive Physiology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Insulin-like growth factor-1 (IGF-1) plays a crucial role in follicular growth and stimulates steroid hormone production in bovine follicles. Steroid hormones are synthesized through the actions of steroidogenic enzymes, specifically STAR, CYP11A1, HSD3B, and CYP19A1 in both theca cells (TCs) and granulosa cells (GCs), under the influence of gonadotropins. Particularly, estradiol 17 beta (E2) assumes a central role in follicular development and selection by activating estrogen receptors beta (ESR2) in GCs. We assessed ESR2 mRNA expression in GCs of developing follicles and investigated the impact of IGF-1 on the mRNA expression of ESR2, CYP19A1, FSHR, and LHCGR, STAR, CYP11A1, and HSD17B in cultured GCs and TCs, respectively. Additionally, we assessed the influence of IGF-1 on androstenedione (A4), progesterone (P4), and testosterone (T) production in TCs. Small-sized follicles (< 6 mm) exhibited the highest levels of ESR2 mRNA expression, whereas medium-sized follicles (7-8 mm) displayed higher levels than large-sized follicles (>= 9 mm) (P < 0.05). IGF-1 increased the mRNA expression of ESR2, CYP19A1, and FSHR in GCs of follicles of both sizes, except for FSHR mRNA in medium-sized follicles (P < 0.05). IGF-1 significantly elevated mRNA expression of LHCGR, STAR, CYP11A1, and CYP17B in TCs of small-and medium-sized follicles (P < 0.05). Moreover, IGF-1 augmented the production of A4 and P4 but had no impact on T production in TCs of small-and medium-sized follicles. Taken together, our findings indicate that IGF-1 upregulates steroidogenic enzymes and steroid hormone production, underscoring the crucial role of IGF-1 in follicle development and selection. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males 635 645 EN Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Kazunori Okamura Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Masaki Hasegawa Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Satoshi Tanaka Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Shusaku Kanai Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Original Article 10.18926/AMO/66156 In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1867-1071 40 11 2022 Percutaneous cryoablation for clinical T3a renal cell carcinoma (< 7 cm) with segmental vein involvement or perinephric fat invasion based on preoperative evaluation of high-resolution multidetector computed tomography scan 1201 1209 EN Mayu Uka Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Toshihiro Iguchi Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Nanako Okawa Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yusuke Matsui Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Koji Tomita Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Noriyuki Umakoshi Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kazuaki Munetomo Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Hideo Gobara Division of Medical Informatics, Okayama University Hospital Motoo Araki Department of Urology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Takao Hiraki Department of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Purpose　To retrospectively assess the feasibility, safety, renal function, technique efficacy rate, and survival of patients with clinical T3a renal cell carcinoma (RCC). Materials and methods　Sixteen cryoablation sessions were performed in 14 patients (10 men; mean age, 69.8 ± 10.5 years; range, 49–90 years) with 14 clear cell T3a RCCs (mean, 3.3 ± 0.9 cm; range, 1.9–5.2 cm). One patient was on dialysis. Transcatheter arterial embolization was performed before cryoablation in 15 sessions. The primary endpoint was the technique efficacy rate. The secondary endpoints included feasibility, safety, renal function, and survival. Results　Cryoablation was technically successful in all RCC cases. In two RCCs, cryoablation was performed twice because of local tumor progression. No major adverse events were observed. All patients were alive without metastases, with a median follow-up of 45 months (6－93 months). Complete response was achieved by cryoablation in 11 RCCs (78.6%). The primary and secondary technique efficacy rates were 77.1% and 84.4% at 1 year, 57.9% and 73.9% at 3 years, and 57.9% and 73.9% at 5 years, respectively. One patient underwent dialysis given a total contralateral nephrectomy due to another RCC 1 month after initial cryoablation and a total ipsilateral nephrectomy 46 months after initial cryoablation due to local progression. Except for two dialysis patients, of the 12 patients with a median follow-up of 41 months (6–93 months), none were on dialysis. Conclusion　Cryoablation was safe and effective in T3a RCC, which mainly involved the renal venous branches and may represent an alternative treatment for inoperable patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient 553 559 EN Takahiro Murokawa Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Kenta Sui Department of Gastroenterological Surgery, Kochi Health Sciences Center Kazuhide Ozaki Department of Gastroenterological Surgery, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Hiroshi Yoshida Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School Case Report 10.18926/AMO/65979 Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries 499 509 EN Yuji Hatakeyama Department of Orthopaedic Surgery, Akita Red Cross Hospital Michio Hongo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Tadato Kido Department of Orthopaedic Surgery, Akita Rosai Hospital Masakazu Urayama Department of Orthopaedic Surgery, Ogachi Central Hospital Yuji Kasukawa Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Hiroshi Sasaki Department of Orthopaedic Surgery, Noshiro Kousei Medical Center Toshiaki Aizawa Department of Orthopaedic Surgery, Kitaakita Municipal Hospital Daisuke Kudo Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Ryota Kimura Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Yuichi Ono Department of Orthopaedic Surgery, Akita Red Cross Hospital Fumihito Kasama Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Naohisa Miyakoshi Department of Orthopaedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65972 This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Childcare and Child Development in Japan 479 490 EN Akiko Murata Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naomi Matsumoto Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Miyaji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Yorifuji Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/65970 For decades, the notion has persisted in developed countries that exclusive care by the mothers is best for the development of children up to 3 years of age. To examine the veracity of this “myth of the first three years” in Japan, we examined the effects of childcare facility use for children younger than 3 years on their development using the cohorts of the Longitudinal Survey of Newborns in the 21st Century conducted in Japan. Of the 47,015 respondents to the survey, we studied the children of 5,508 mothers with university/professional education to evaluate the relationships between primary early (< 2.5 years) childcare providers during weekday daytime hours and specific development indices for the ages of 2.5, 5.5, and 8 years. At the age of 2.5 and 5.5 years, children attending childcare facilities were judged as having more advanced developmental behaviors by their parents, such as being able to compose a two-word sentence (adjusted odds ratio [aOR]: 0.22) or to express emotions (aOR: 0.81), compared with those cared for by mothers. However, at the age of 8 years, children who attended childcare facilities as infants < 2.5 years showed more aggressive behavior in interrupting people (aOR: 1.20) and causing disturbances in public (aOR: 1.26) than those cared for by mothers (after adjustment for numerous child and parental factors). Although these results are generally consistent with previous studies, issues potentially involved with problem behavior such as quality of childcare require further investigation, as does the case of children of mothers with more modest educational attainment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Low Patient Weight and Long Intubation Time Are Key Factors for Pain during Colonoscopy 471 478 EN Shohei Oka Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Harada Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shumpei Yamamoto Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Yasutomi Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoko Igawa Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayasu Ohmori Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Hirai Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Departments of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65969 Although the clinical usefulness of colonoscopy has been established, the procedure remains painful for many patients. This study was designed to clarify the factors predicting colonoscopy-related pain. We evaluated 283 consecutive patients who completed a first-ever, total colonoscopy without sedatives or analgesics. The severity of pain symptoms was evaluated by a numeric rating scale (NRS) in a questionnaire immediately after the colonoscopy. Patient backgrounds and endoscopic findings were analyzed to evaluate their association with pain. Out of 283 patients, 53 scored their pain 0-1 on the NRS while 48 scored it 6-10. We defined the colonoscopies of the former and latter patients as painless and painful, respectively, and compared the two. Multivariate analyses revealed that low body weight (OR 4.95, 95%CI 1.89-12.99) and longer intubation time (OR 3.63, 95%CI 1.46-9.03) were significant risk factors for painful colonoscopy. To identify factors contributing to the increased intubation time, we divided subjects into short- and long-intubation-time groups based on a median insertion time of 7 min. Older age (OR 2.28, 95%CI 1.31-3.98), previous abdominal surgery (OR 1.93, 95%CI 1.13-3.32) and findings of invasive cancer (OR 10.90, 95%CI 1.34-88.90) were significant factors for longer intubation time. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0022-2623 65 8 2022 Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo 6039 6055 EN Negar Khazan Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Kyu Kwang Kim Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Jeanne N. Hansen Department of Pediatrics, University of Rochester Medical Center Niloy A. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Taylor Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Cameron W. A. Snyder Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Ravina Pandita Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Myla Strawderman Department of Biostatistics and Computational Biology, University of Rochester Medical Center Michiko Fujihara Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuta Takamura Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ye Jian Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nicholas Battaglia Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Naohiro Yano Department of Surgery, Division of Surgical Research, Rhode Island Hospital, Alpert Medical School of Brown University Yuki Teramoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center Leggy A. Arnold Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee Russell Hopson Department of Chemistry, Brown University Keshav Kishor Department of Chemistry, Birla Institute of Technology Sneha Nayak Department of Chemistry, Birla Institute of Technology Debasmita Ojha Department of Chemistry, Birla Institute of Technology Ashoke Sharon Department of Chemistry, Birla Institute of Technology John M. Ashton Genomics Core Facility, Wilmot Cancer Center, University of Rochester Medical Center Jian Wang Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Michael T. Milano Department of Radiation Oncology, University of Rochester Medical Center Hiroshi Miyamoto Department of Pathology and Laboratory Medicine, University of Rochester Medical Center David C. Linehan Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Scott A. Gerber Division of Surgery and of Microbiology and Immunology, University of Rochester Medical Center Nada Kawar Center for Breast Health and Gynecologic Oncology, Mercy Medical Center Ajay P. Singh Rutgers, The State University of New Jersey Erdem D. Tabdanov CytoMechanobiology Laboratory, Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University Nikolay V. Dokholyan Department of Pharmacology and Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Penn State University Hiroki Kakuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peter W. Jurutka School of Mathematical and Natural Sciences, Arizona State University, Health Futures Center Nina F. Schor Departments of Pediatrics, Neurology, and Neuroscience, University of Rochester Medical Center Rachael B. Rowswell-Turner Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Rakesh K. Singh Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Richard G. Moore Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1873-9601 17 4 2023 Expression and function of CCN2-derived circRNAs in chondrocytes 1501 1515 EN Soma Kato Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumi Kawata Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Nishida Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomomi Mizukawa Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Seiji Iida Department of Oral Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Cellular communication network factor 2 (CCN2) molecules promote endochondral ossification and articular cartilage regeneration, and circular RNAs (circRNAs), which arise from various genes and regulate gene expression by adsorbing miRNAs, are known to be synthesized from CCN2 in human vascular endothelial cells and other types of cells. However, in chondrocytes, not only the function but also the presence of CCN2-derived circRNA remains completely unknown. In the present study, we investigated the expression and function of CCN2-derived circRNAs in chondrocytes. Amplicons smaller than those from known CCN2-derived circRNAs were observed using RT-PCR analysis that could specifically amplify CCN2-derived circRNAs in human chondrocytic HCS-2/8 cells. The nucleotide sequences of the PCR products indicated novel circRNAs in the HCS-2/8 cells that were different from known CCN2-derived circRNAs. Moreover, the expression of several Ccn2-derived circRNAs in murine chondroblastic ATDC5 cells was confirmed and observed to change alongside chondrocytic differentiation. Next, one of these circRNAs was knocked down in HCS-2/8 cells to investigate the function of the human CCN2-derived circRNA. As a result, CCN2-derived circRNA knockdown significantly reduced the expression of aggrecan mRNA and proteoglycan synthesis. Our data suggest that CCN2-derived circRNAs are expressed in chondrocytes and play a role in chondrogenic differentiation. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-230X 23 1 2023 The efficacy of non-anesthesiologist-administered propofol sedation with a target-controlled infusion system during double-balloon endoscopic retrograde cholangiopancreatography 296 EN Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Taisuke Obata Department of Gastroenterology and Hepatology, Okayama University Hospital Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Hospital Taiji Ogawa Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background　The sedation method used during double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) differs among countries and/or facilities, and there is no established method. This study aimed to evaluate the efficacy of non-anesthesiologist-administered propofol (NAAP) sedation using a target-controlled infusion (TCI) system during DB-ERCP. Methods　This retrospective study was conducted between May 2017 and December 2020 at an academic center. One hundred and fifty-six consecutive patients who underwent DB-ERCP were sedated by gastroenterologists using diazepam (n = 77) or propofol with a TCI system (n = 79), depending on the period. The primary endpoint was a comparison of poor sedation rates between the two groups. Poor sedation was defined as a condition requiring the use of other sedative agents or discontinuation of the procedure. Secondary endpoints were sedation-related adverse events and risk factors for poor sedation. Results　Poor sedation occurred significantly more often in the diazepam sedation group (diazepam sedation, n = 12 [16%] vs. propofol sedation, n = 1 [1%]; P = 0.001). Vigorous body movements (3 or 4) (diazepam sedation, n = 40 [52%] vs. propofol sedation, n = 28 [35%]; P = 0.038) and hypoxemia (< 85%) (diazepam sedation, n = 7 [9%] vs. propofol sedation, n = 1 [1%]; P = 0.027) occurred significantly more often in the diazepam sedation group. In the multivariate analysis, age < 70 years old (OR, 10.26; 95% CI, 1.57-66.98; P = 0.015), BMI = 25 kg/m2 (OR, 11.96; 95% CI, 1.67-85.69; P = 0.014), and propofol sedation (OR, 0.06; 95% CI, 0.01-0.58; P = 0.015) were associated factors for poor sedation. Conclusions　NAAP sedation with the TCI system during DB-ERCP was safer and more effective than diazepam sedation. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2405-8440 9 8 2023 Bayesian statistical modeling to predict observer-specific optimal windowing parameters in magnetic resonance imaging e19038 EN Kohei Sugimoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masataka Oita Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masahiro Kuroda Department of Radiological Technology, Faculty of Health Sciences, Okayama University Magnetic resonance (MR) images require a process known as windowing for optimizing the display conditions. However, the conventional windowing process often fails to achieve the preferred display conditions for observers due to various factors. This study proposes a novel framework for predicting the preferred windowing parameters for each observer using Bayesian statistical modeling. MR images obtained from 1000 patients were divided into training and test sets at a 7:3 ratio. The image intensity and windowing parameters were standardized using previously reported methods. Bayesian statistical modeling was utilized to predict the windowing parameters preferred by three MR imaging (MRI) operators. The performance of the proposed framework was evaluated by assessing the mean relative error (MRE), mean absolute error (MAE), and Pearson's correlation coefficient (ρ) of the test set. In addition, the naive method, which presumes that the average value of the windowing parameters for each acquisition sequence and body region in the training set is optimal, was also used for comparison. Three MRI operators and three radiologists conducted visual assessments. The mean MRE, MAE, and ρ values for the window level and width (WL/WW) in the proposed framework were 12.6 and 13.9, 42.9 and 85.4, and 0.98 and 0.98, respectively. These results outperformed those obtained using the naive method. The visual assessments revealed no significant differences between the original and predicted display conditions, indicating that the proposed framework accurately predicts individualized windowing parameters with the additional advantages of robustness and ease of use. Thus, the proposed framework can effectively predict the windowing parameters preferred by each observer. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2692-4609 2 1 2021 Endoscopic removal of proximally migrated stents using a double-balloon enteroscope in patients with bowel reconstruction (with video) e32 EN Takashi Oda Department of Gastroenterology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Hospital Eijiro Ueta Department of Gastroenterology, Okayama University Hospital Hitomi Himei Department of Gastroenterology, Okayama University Hospital Taiji Ogawa Department of Gastroenterology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology, Okayama University Hospital Yuki Fujii Department of Gastroenterology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology, Okayama University Hospital Hironari Kato Department of Gastroenterology, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology, Okayama University Hospital Endoscopic migrated stent removal using a balloon-assisted enteroscope is technically difficult in patients with bowel reconstruction. We report the treatment outcomes and endoscopic removal methods for migrated stents using a double-balloon enteroscope (DBE). We retrospectively studied 12 patients with stent migration into the main pancreatic duct (MPD) or bile duct who underwent bowel reconstruction between January 2012 and June 2020. The successful removal rates in the MPD (n = 3) and the bile duct (n = 9) were 66.7% (2/3) and 88.9% (8/9), respectively. The removal techniques included the indirect method (n = 3), the direct method (n = 4), and a combination of indirect and direct methods (n = 3). The removal devices included an extraction balloon catheter (n = 7), basket catheter (n = 5), biopsy forceps (n = 3), and snare (n = 2). Stent removal using a DBE was feasible and useful as the first treatment for patients with bowel reconstruction. The choice of the direct and/or indirect method according to the situation of the migrated stent is important. No potential conflict of interest relevant to this article was reported.

IOP Publishing Ltd Acta Medica Okayama 2041-8205 951 2 2023 Search for Astrophysical Electron Antineutrinos in Super-Kamiokande with 0.01% Gadolinium-loaded Water L27 EN M. Harada Department of Physics, Okayama University We report the first search result for the flux of astrophysical electron antineutrinos for energies O(10) MeV in the gadolinium-loaded Super-Kamiokande (SK) detector. In 2020 June, gadolinium was introduced to the ultrapure water of the SK detector in order to detect neutrons more efficiently. In this new experimental phase, SK-Gd, we can search for electron antineutrinos via inverse beta decay with efficient background rejection thanks to the high efficiency of the neutron tagging technique. In this paper, we report the result for the initial stage of SK-Gd, during 2020 August 26, and 2022 June 1 with a 22.5 x 552 kton center dot day exposure at 0.01% Gd mass concentration. No significant excess over the expected background in the observed events is found for the neutrino energies below 31.3 MeV. Thus, the flux upper limits are placed at the 90% confidence level. The limits and sensitivities are already comparable with the previous SK result with pure water (22.5 x 2970 kton center dot day) owing to the enhanced neutron tagging. Operation with Gd increased to 0.03% started in 2022 June. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia 395 405 EN Marko Pavlovic University Hospital Center Mostar, University of Mostar Dragan Babic University Hospital Center Mostar, University of Mostar Pejana Rastovic University Hospital Center Mostar, University of Mostar Jurica Arapovic University Hospital Center Mostar, University of Mostar Marko Martinac Health Care Center Mostar, University of Mostar Sanja Jakovac University Hospital Center Mostar, University of Mostar Romana Barbaric University Hospital Center Mostar, University of Mostar Original Article 10.18926/AMO/65750 We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=－0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=－0.258, t=－2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=－0.247, p=0.019) and antipsychotic treatment duration (ρ=－0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan 387 394 EN Takahiro Kataoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Hiroshi Habu Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayumi Tanaka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Shota Naoe Department of Radiological Technology, Okayama University Graduate School of Health Sciences Kaito Murakami Department of Radiological Technology, Okayama University Graduate School of Health Sciences Yuki Fujimoto Department of Radiological Technology, Okayama University Graduate School of Health Sciences Ryohei Yukimine Department of Radiological Technology, Okayama University Graduate School of Health Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumihiro Mitsunobu Department of Longevity and Social Medicine (Geriatrics), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyonori Yamaoka Department of Radiological Technology, Okayama University Graduate School of Health Sciences Original Article 10.18926/AMO/65749 No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants’ bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis. No potential conflict of interest relevant to this article was reported.

Japan Atherosclerosis Society Acta Medica Okayama 1340-3478 30 12 2023 Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119) 1927 1949 EN Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoko Naoe Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. Hiroyuki Wakabayashi Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. Takashi Yano Medical Affairs Department, Mochida Pharmaceutical Co., Ltd. Takuya Mori Clinical Research Department, Mochida Pharmaceutical Co., Ltd. Shingo Kanda Clinical Development Planning and Management Department, Mochida Pharmaceutical Co., Ltd. Makoto Arita Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119. Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated. Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted. Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Relationship between the Arthroscopic Findings and Pathology of Greater Trochanteric Pain Syndrome 371 375 EN Yosuke Iwamoto Department of Orthopedic Surgery, Akita University Graduate School of Medicine Mitsunori Kaya Kaya Orthopedic Surgery Sports Clinic Hiroaki Kijima Department of Orthopedic Surgery, Akita University Graduate School of Medicine Masashi Fujii Akita Hip Research Group Itsuki Nagahata Akita Hip Research Group Naohisa Miyakoshi Department of Orthopedic Surgery, Akita University Graduate School of Medicine Original Article 10.18926/AMO/65746 In recent publications on greater trochanteric pain syndrome (GTPS), the pathology receiving the most attention has been gluteus medius muscle tendinous injury, and surgical techniques such as gluteus medius tendon repair and their outcomes for GTPS have been reported. In our department-related facilities, arthroscopic surgeries are routinely performed for the patients with recalcitrant GTPS. A total of 51 patients were diagnosed with GTPS. Surgical treatment was carried out 22 patients (24 joints; 4 males and 18 females; mean age at surgery of 52.0 years). Arthroscopic findings confirmed bursitis in all 24 joints. In all cases, debridement of the greater trochanter bursa provided rapid relief of greater trochanter pain. The Numerical Rating Scale showed significant improvement, from the preoperative mean of 7.8 (range, 6-10) to the postoperative day 7 mean of 1.6 (range, 0-3). The modified Harris Hip Score was significantly improved from the preoperative mean of 65.5 (range, 52.5-78.3) to the final follow-up (average 2.9 months) mean of 96.0 (range, 85.2-100). Fascial damage of the gluteus medius muscle was observed in 21 joints while only 2 patients had a gluteus medius tendinous injury. Greater trochanteric bursitis and fascia or muscle-fiber injury of the gluteus medius muscle are the most common pathologies in patients with lateral hip pain. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients 347 357 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahide Takahashi Division of Medical Support, Okayama University Hospital Araki Hirabata Division of Medical Support, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65740 The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis 341 345 EN Motoyuki Otsuka Department of Gastroenterology and Hepatology, Academic Field of Medicine, Density and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/65739 Hepatitis B virus is a pathogenic virus that infects 300 million people worldwide and causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Hepatitis B virus encodes four proteins. Among them, the HBx protein plays a central role in the HBV pathogenesis. Because the HBx protein is considered to play a central role in the induction of viral replication and hepatocarcinogenesis, the regulation of its function could be a key factor in the development of new interventions against hepatitis B. In this review, HBx protein-related viral replication and hepatocarcinogenesis mechanisms are described, with a focus on the recently reported viral replication mechanisms related to degradation of the Smc5/6 protein complex. We also discuss our recent discovery of a compound that inhibits HBx protein-induced degradation of the Smc5/6 protein complex, and that exerts inhibitory effects on both viral replication and hepatocarcinogenesis. Finally, prospects for future research on the HBx protein are described. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 12 10 2023 Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome e028706 EN Yoshimasa Morimoto Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Background: The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. Methods and Results: Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. Conclusions: The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma 323 330 EN Keigo Makino Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joji Ishida Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichiro Hirano Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuki Suruga Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kana Washio Departments of Pediatrics, Okayama University Hospital Kenji Nishida Departments of Pathology, Okayama University Hospital Hiroyuki Yanai Departments of Pathology, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65502 In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Usefulness of Simple Diffusion Kurtosis Imaging for Head and Neck Tumors: An Early Clinical Study 273 280 EN Yudai Shimizu Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Fukumura Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Satoshi Imajoh Radiological Technology, Graduate School of Health Sciences, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Babatunde O. Bamgbose Department of Oral Diagnostic Sciences, Faculty of Dentistry, Bayero University Yoshinobu Yanagi Department of Dental Informatics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/65492 Diffusion kurtosis (DK) imaging (DKI), a type of restricted diffusion-weighted imaging, has been reported to be useful for tumor diagnoses in clinical studies. We developed a software program to simultaneously create DK images with apparent diffusion coefficient (ADC) maps and conducted an initial clinical study. Multi-shot echo-planar diffusion-weighted images were obtained at b-values of 0, 400, and 800 sec/mm2 for simple DKI, and DK images were created simultaneously with the ADC map. The usefulness of the DK image and ADC map was evaluated using a pixel analysis of all pixels and a median analysis of the pixels of each case. Tumor and normal tissues differed significantly in both pixel and median analyses. In the pixel analysis, the area under the curve was 0.64 for the mean kurtosis (MK) value and 0.77 for the ADC value. In the median analysis, the MK value was 0.74, and the ADC value was 0.75. The MK and ADC values correlated moderately in the pixel analysis and strongly in the median analysis. Our simple DKI system created DK images simultaneously with ADC maps, and the obtained MK and ADC values were useful for differentiating head and neck tumors from normal tissue. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy 263 272 EN Yusheng Guo Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Kosaka Department of Anesthesiology and Resuscitology, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65491 Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative (< 0 mL) and positive (> 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Withdrawal from Hemodialysis in a Patient with IgD Type Multiple Myeloma: A Case-based Review 221 225 EN Hiroki Iriyoshi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Ken-ei Sada Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Atsushi Miyauchi Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Hirotaka Yamamoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Daisuke Hashimoto Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shigeru Nojima Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Shingo Yamanaka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Masafumi Kawamura Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Satoshi Oka Department of Internal Medicine, Kochi Prefectural Hata-Kenmin Hospital Case Report 10.18926/AMO/65154 Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Case Series of Granulicatella Bacteremia: A Single-centered, Five-year Retrospective Study 203 207 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoharu Ishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Nagaoka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kou Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65151 Granulicatella species are rare, nutritionally variant streptococci that cause infective endocarditis. Their clinical and microbiological characteristics remain unknown. We reviewed five years of Granulicatella cases in our hospital database (Jan 2017-Jun 2022), finding 6 Granulicatella adiacens cases and 1 Granulicatella elegans case. Clinical backgrounds and bacteremia sources were diverse; 3 cases developed polymicrobial bacteremia. Antimicrobial testing showed non-susceptibility to penicillin G in 4 of 7 cases (57.1%), and high susceptibility to carbapenems and vancomycin in all cases. Determining optimal antibiotic therapy for Granulicatella infections is vital in this era of antimicrobial resistance. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Fracture Line Distributions of Undisplaced Distal Radius Fractures in Relation to Rupture of the Extensor Pollicis Longus Tendon 179 184 EN Hidenori Kondo Department of Orthopaedic Surgery, Kagawa Rosai Hospital Taichi Saito Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasunori Shimamura Department of Sports Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryozo Harada Department of Orthopaedic Surgery, Kurashiki Sweet Hospital Junya Imatani Department of Orthopaedic Surgery, Saiseikai General Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65147 Rupture of the extensor pollicis longus (EPL) tendon is a known complication after undisplaced distal radius fracture (DRF). However, no report has revealed the relationship between EPL tendon rupture and the fracture pattern. Thus, this study aimed to investigate the characteristics of fractures at risk of EPL tendon rupture using fracture line mapping of undisplaced DRFs. This study used computed tomography imaging data of undisplaced DRFs with (n=18) and without EPL tendon rupture (n=52). Fracture lines obtained from 3D reconstruction data were drawn manually after matching with a 2D template wrist model. Fracture maps represented the fracture line distribution by superimposing the fracture lines of all 70 patients. Heat maps showed the relative frequency of the fracture lines as a gradual color change. Fracture lines of cases with EPL tendon rupture were concentrated in the proximal border of Lister’s tubercle. By contrast, fracture lines of cases without EPL tendon rupture were relatively dispersed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Personalized Preclinical Training in Dental Ergonomics and Endodontics in Undergraduate Dentistry Students (Pilot Study) 147 159 EN Zulema Arias Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Stephanie Haines Department of Health Tadashi Yamamoto Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kazu Hatanaka Department of Periodontics and Endodontics, Okayama University Hospital Keisuke Yamashiro Department of Periodontics and Endodontics, Okayama University Hospital Norihiro Sonoi Department of Periodontics and Endodontics, Okayama University Hospital Shogo Takashiba Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65144 The curriculum at the Department of Pathophysiology in the Periodontal Sciences program at Okayama University includes normative preclinical training (NPT) using phantoms. NPT is given to the whole class of 5 th year students divided in groups of 8 students/instructor. In 2019, an innovative personalized preclinical training (PPT) pilot study was implemented for this group of students whereby two students, each with their own dental unit, were coached by one instructor. The main topics covered were dental ergonomics and endodontics. We aimed to evaluate the effectiveness of PPT in dental ergonomics and endodontics toward increasing the knowledge and future clinical skills of students who had already undergone NPT. A test on endodontics was taken before and after PPT. A questionnaire was completed to assess their perception of improvement regarding the above-mentioned topics. Test scores and questionnaire results both showed that the students’ level of knowledge and awareness of future clinical skills was significantly higher after PPT. This pilot study demonstrated that PPT increased the students’ knowledge and future clinical skills. As preclinical training forms the foundation for clinical practice, investment in future research regarding this personalized approach is likely to enhance students’ understanding and clinical performance. No potential conflict of interest relevant to this article was reported.

岡山大学全学教育・学生支援機構 Acta Medica Okayama 2432-9665 7 2023 小学校における大学留学生と児童の交流活動 ―小学校教諭の語りの分析ー 87 106 EN Masumi Nagano 10.18926/64999 本稿では，大学の留学生と小学校の児童との交流活動の事例2件を取り上げ，実践者である小学校教諭が交流活動に何を期待し，何を重視していたか，また，どのような成果や課題を見出したかについて，教諭の語りの分析をもとに明らかにすることを目的とした。分析の結果，留学生との交流活動を通じて，異なる言語や文化的背景を持つ他者に対する児童のある種の構えが低減することが期待され，交流活動中に児童が感じる喜びややりがい，留学生に対する興味や親近感など，交流活動が児童の情意面に与える影響が成果として注目されることが示された。同時に，交流活動における体験的な学びと，その他の学習活動を有機的に組み合わせようとする教諭の狙いがうかがえた。 No potential conflict of interest relevant to this article was reported.

ROYAL SOC CHEMISTRY Acta Medica Okayama 2046-2069 13 8 2023 Convergent evolution of animal and microbial rhodopsins 5367 5381 EN Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rhodopsins, a family of photoreceptive membrane proteins, contain retinal as a chromophore and were firstly identified as reddish pigments from frog retina in 1876. Since then, rhodopsin-like proteins have been identified mainly from animal eyes. In 1971, a rhodopsin-like pigment was discovered from the archaeon Halobacterium salinarum and named bacteriorhodopsin. While it was believed that rhodopsin- and bacteriorhodopsin-like proteins were expressed only in animal eyes and archaea, respectively, before the 1990s, a variety of rhodopsin-like proteins (called animal rhodopsins or opsins) and bacteriorhodopsin-like proteins (called microbial rhodopsins) have been progressively identified from various tissues of animals and microorganisms, respectively. Here, we comprehensively introduce the research conducted on animal and microbial rhodopsins. Recent analysis has revealed that the two rhodopsin families have common molecular properties, such as the protein structure (i.e., 7-transmembrane structure), retinal structure (i.e., binding ability to cis- and trans-retinal), color sensitivity (i.e., UV- and visible-light sensitivities), and photoreaction (i.e., triggering structural changes by light and heat), more than what was expected at the early stages of rhodopsin research. Contrastingly, their molecular functions are distinctively different (e.g., G protein-coupled receptors and photoisomerases for animal rhodopsins and ion transporters and phototaxis sensors for microbial rhodopsins). Therefore, based on their similarities and dissimilarities, we propose that animal and microbial rhodopsins have convergently evolved from their distinctive origins as multi-colored retinal-binding membrane proteins whose activities are regulated by light and heat but independently evolved for different molecular and physiological functions in the cognate organism. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 1 2022 令和２年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 7 9 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Development, Disappearance, and Clinical Course of Melanosis Coli: Sex Differences in the Progression of Severity 57 64 EN Ryo Katsumata Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Noriaki Manabe Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Yasumasa Monobe Pathology, Kawasaki Medical School General Medical Center Maki Ayaki Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Mitsuhiko Suehiro Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Minoru Fujita Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center Tomoari Kamada Health Care Medicine, Kawasaki Medical School General Medical Center Hirofumi Kawamoto Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Ken Haruma Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center Original Article 10.18926/AMO/64362 Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 The Efficacy of Inflammatory and Immune Markers for Predicting the Prognosis of Patients with Stage IV Breast Cancer 37 43 EN Kosho Yamanouchi Department of Surgery, National Hospital Organization, Nagasaki Medical Center Shigeto Maeda Department of Surgery, National Hospital Organization, Nagasaki Medical Center Original Article 10.18926/AMO/64360 Systemic therapy for stage IV breast cancer is usually an initial treatment and is based on findings regarding biomarkers (e.g., hormone receptors and human epidermal growth factor receptor-2 [HER2]). However, the response to therapy and outcomes sometime differ among patients with similar prognostic factors including grade, hormone receptor, HER2, and more. We conducted retrospective analyses to evaluate the correlations between the overall survival (OS) of 46 stage IV breast cancer patients and (i) the peripheral absolute lymphocyte count (ALC) and (ii) composite blood cell markers. The peripheral blood cell markers included the neutrophil- to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the most recently introduced indicator, the pan-immune-inflammatory value (PIV). The SIRI and PIV showed prognostic impacts on the patients: those with a low SIRI or a low PIV showed significantly better OS than those with a high SIRI (5-year, 66.0% vs. 35.0%, p<0.05) or high PIV (5-year, 68.1% vs. 38.5%, p<0.05), respectively. This is the first report indicating the possible prognostic value of the PIV for OS in patients with stage IV breast cancer. Further studies with larger numbers of patients are necessary for further clarification. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B (inducible MLSB) Resistance in Clindamycin-Susceptible Staphylococcus aureus at Okayama University Hospital 1 9 EN Lutfun Nahar Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64355 Inducible resistance to the macrolide, lincosamide, and streptogramin B (iMLSB) antibiotic family is a latent mechanism for antimicrobial resistance in Staphylococcus aureus. We here investigated the frequency and genotypic profiles of iMLSB resistance in clindamycin (CLDM)-susceptible S. aureus isolated in Okayama University Hospital from June 2020 to June 2021. We phenotypically screened the iMLSB resistance via D-zone test and performed PCR testing for the erythromycin ribosomal methylase (erm) genes: ermA and ermC. Among 432 CLDM-susceptible S. aureus isolates, 138 (31.9%) exhibited an iMLSB-resistance phenotype, with methicillinresistant S. aureus isolates (MRSA; 61 isolates: 58.6%) exhibiting higher positivity than methicillin-sensitive S. aureus isolates (MSSA; 77 isolates: 23.5%) (p<0.001). Male patients had a higher frequency of iMLSB resistance than females (OR [95%CI]: 1.8 [1.2-2.8]; p=0.007). Genotypically, ermA predominated in both MSSA (70.1%) and MRSA (86.9%) compared to ermC (14.3% in MSSA and 11.5% in MRSA). A single strain of MRSA possessed both ermA and ermC, while 12 (15.6%) MSSA isolates were negative for both ermA and ermC, suggesting the presence of other genetic mechanisms. Collectively, these results show that approximately 33% of CLDM-susceptible S. aureus isolates at our university hospital exhibited iMLSB resistance, predominantly caused by ermA in both MSSA and MRSA. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 112 2023 Effect of seed cold PEG–priming concentration and period followed by re–drying on germination, growth and flowering of Eustoma grandiflorum （Raf.） Shinn ʻExe Lavenderʼ 7 12 EN Thao Thu Phan Graduate School of Environmental and Life Science, Okayama University Keigo Fukushima Hiroshima Prefectural Technology Research Institute, Agricultural Technology Research Center Yoshiyuki Tanaka Graduate School of Environmental and Life Science, Okayama University Ken-ichiro Yasuba Graduate School of Environmental and Life Science, Okayama University Yuichi Yoshida Graduate School of Environmental and Life Science, Okayama University Tanjuro Goto Graduate School of Environmental and Life Science, Okayama University This study aimed to investigate whether seed cold priming by PEG‒6000, followed by re‒drying would affect the germination, growth, and flowering of Eustoma ‘Exe Lavender’ raised seedling under high temperatures. Seeds of control treatment were not treated with cold‒priming or re‒drying. In experiment 1, seeds were cold‒primed with water and PEG‒6000 at ‒0.75 and ‒1.5 MPa for 5 weeks at 10°C in the dark and then subjected to re‒dried and storage for 30 days at 10°C. The results showed that cold‒primed seeds germinated earlier than those of the control. Compared to water treatment, plants grown from PEG‒6000 treatments and re‒drying showed similar germination rate, bolting rate, days to bolting, bolting node and flowering rate. In experiment 2, cold priming periods by water and ‒1.5 MPa PEG‒6000 were investigated for 4, 5, 6, 7, and 8 weeks. ‘Exe Lavender’ seeds treated with cold water and in the dark for longer than 5 weeks increased their percentage of radicle emergence and decreased germination rate after 30 days of re‒drying and storage. Meanwhile, those treated with cold-PEG did not protrude the radicle even for 8 weeks of priming and maintained the germination rate after re‒drying and storage. Days to bolting and days to flowering tended to decrease when the priming period decreased. The results suggest that the seed cold priming treatment by ‒1.5 MPa PEG‒6000 and subsequent re‒drying improved germination rate and maintained bolting rate and flowering rate in Eustoma compared to cold priming treatment by water raised seedling under high temperature conditions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus 705 713 EN Toshihiro Higashikawa Kanazawa Medical University Himi Municipal Hospital Tomohiko Ito Kanazawa Medical University Himi Municipal Hospital Takurou Mizuno Kanazawa Medical University Himi Municipal Hospital Keiichiro Ishigami Kanazawa Medical University Himi Municipal Hospital Kengo Kuroki Kanazawa Medical University Himi Municipal Hospital Naoto Maekawa Kanazawa Medical University Himi Municipal Hospital Daisuke Usuda Kanazawa Medical University Himi Municipal Hospital Toshihide Izumida Kanazawa Medical University Himi Municipal Hospital Shinya Yamada Kanazawa Medical University Himi Municipal Hospital Ryusho Sangen Kanazawa Medical University Himi Municipal Hospital Kazu Hamada Kanazawa Medical University Himi Municipal Hospital Jun Kiyosawa Kanazawa Medical University Himi Municipal Hospital Atsushi Saito Kanazawa Medical University Himi Municipal Hospital Masaharu Iguchi Kanazawa Medical University Himi Municipal Hospital Yuji Kasamaki Kanazawa Medical University Himi Municipal Hospital Takeshi Nakahashi Kanazawa Medical University Himi Municipal Hospital Akihiro Fukuda Kanazawa Medical University Himi Municipal Hospital Hitoshi Saito Kanazawa Medical University Himi Municipal Hospital Tsugiyasu Kanda Kanazawa Medical University Himi Municipal Hospital Masashi Okuro Department of Geriatric Medicine, Kanazawa Medical University Original Article 10.18926/AMO/64121 The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=－0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=－0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=－0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients 695 703 EN Hideki Onishi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Nouso Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Oyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Adachi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64120 This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 An Evaluation of the Efficacy of Compression Therapy Using Sleeves and Stockings to Prevent Docetaxel-induced Peripheral Neuropathy in Breast Cancer Patients 689 694 EN Kosho Yamanouchi Department of Surgery, Nagasaki University Graduate School of Biomedical Science Sayaka Kuba Department of Surgery, Nagasaki University Graduate School of Biomedical Science Megumi Matsumoto Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Hiroshi Yano Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Michi Morita Department of Surgery, Nagasaki University Graduate School of Biomedical Science Chika Sakimura Department of Surgery, Nagasaki University Graduate School of Biomedical Science Ryota Otsubo Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Masaaki Hidaka Department of Surgery, Nagasaki University Graduate School of Biomedical Science Takeshi Nagayasu Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science Susumu Eguchi Department of Surgery, Nagasaki University Graduate School of Biomedical Science Original Article 10.18926/AMO/64119 Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Handling of Germline Findings in Clinical Comprehensive Cancer Genomic Profiling 673 678 EN Mika Okazawa-Sakai Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuko Yamamoto Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center Mashu Futagawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miki Okamura Department of Hereditary Tumors, National Hospital Organization Shikoku Cancer Center Satoko Miyawaki Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center Tomohiro Nishina Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center Kazuhiro Takehara Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center Toshiyuki Kozuki Department of Clinical Research Center, National Hospital Organization Shikoku Cancer Center Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Ichinosuke Hyodo Department of Cancer Genomic Medicine, National Hospital Organization Shikoku Cancer Center Shozo Ohsumi Department of Hereditary Tumors, National Hospital Organization Shikoku Cancer Center Akira Hirasawa Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64117 Patients found to have presumed germline pathogenic variants (PGPVs) during comprehensive genomic profiling (CGP) require genetic counseling (GC) referrals. We retrospectively investigated the outcomes of patients with PGPVs. Among 159 patients who underwent CGP, we recommended GC for the 16 patients with PGPVs (3 with [FG group] and 13 without [G Group] a family/personal history of hereditary cancer) as well as for the 8 patients with no PGPVs, but a history (F group); 2 (67%), 5 (38%), and 3 (38%) patients received GC in the FG, G, and F groups, respectively. Germline testing results were positive in 1 and 2 patients of the FG and G groups, respectively. Among the patients recommended for GC, 58% did not receive GC due to lack of interest, poor performance status, or death. CGP contributes to the identification of germline variants in patients without a history of hereditary cancer. However, the proportion of patients who undergo GC should be improved. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 A Simple and Descriptive Assessment of Morphology Based on the Horizontal Plane of the Pediatric Head and Creation of a Normative Database in Japanese Children 6 Years Old and under: Horizontal Vector Analysis 565 575 EN Sho Komagoe Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Senoo Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Shiraishi Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64038 We herein introduce horizontal vector analysis, a simple method for assessing cranial morphology based on measurement of the head’s horizontal plane, and use this method to establish normal cranial morphology in Japanese children Computed tomography scans taken in 2010-2019 in healthy Japanese children aged ≤ 6 years. The two measurement planes were parallel to the orbitomeatal plane: namely, a plane passing through the dorsum sellae (DS) and the plane superior to that with the maximal area (Max plane). A protractor was used to circumferentially measure the lengths from the central point to the outer surface of the skull. A total of 487 images were extracted. The distances between the DS and Max planes were consistently almost 30 mm for each age group, so we fixed the Max plane as the plane 30 mm superior to the DS plane. Finally, we established datasets of normal values for each age group and sex. Using these norms, perioperative evaluation of various cranial deformities could be performed more easily and circumstantially. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 First-line Combination Strategy Provides Favorable 5-year Outcomes for Patients with Lupus Nephritis: A Single-center Observational Study 547 555 EN Hidetoshi Kagawa Department of Nephrology and Rheumatology, Japanese Red Cross Society Himeji Hospital Ryutaro Yamanaka Department of Nephrology and Rheumatology, Japanese Red Cross Society Himeji Hospital Tsutomu Hiromasa Department of Nephrology and Rheumatology, Japanese Red Cross Society Himeji Hospital Original Article 10.18926/AMO/64036 This observational study aimed to clarify the long-term results of the combination of mizoribine (MZB), tacrolimus (TAC) and prednisolone as first-line therapy for lupus nephritis (LN). This was our institution’s standard therapy between 2009 and 2015, when we saw 36 patients with LN. When a patient thus treated achieved SLEDAI remission (= 0) and/or the prednisolone dose could be tapered to 5 mg/day, either MZB or TAC was stopped, and the other was continued for maintenance therapy. If treatment failure or relapse occurred, second-line therapy was introduced. At years 1 and 5, overall complete renal response and SLEDAI remission were 94% and 88%, and 50% and 62%, respectively. Excluding 2 cases lost to follow-up, medications after 5 years were as follows: 20 (59%) were stable on 1 drug (MZB or TAC), 11 (32%) required continuation of both drugs (MZB + TAC), and 3 (9%) required second-line therapy. The 5-year retention rate was 91% (non-secondline), with 0% of relapse in this group. Our first-line combination strategy showed high remission rates in the induction phase, and subsequent maintenance therapy demonstrated good outcomes for up to 5 years. Research that fine-tunes the order of therapeutic agents and institutes appropriate treatment goals may further improve long-term outcomes for patients with LN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Serum 1,25-dihydroxyvitamin D3 Levels in Patients with Eosinophilic Chronic Rhinosinusitis 527 533 EN Seiichiro Makihara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shotaro Miyamoto Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Kensuke Uraguchi Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aiko Oka Department of Otorhinolaryngology, International University of Health and Welfare, School of Medicine Munechika Tsumura Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Yohei Noda Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otorhinolaryngology, International University of Health and Welfare, School of Medicine Original Article 10.18926/AMO/64033 No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1010-660X 58 10 2022 Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan 1393 EN Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanako Ochi Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Kataoka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Viral Sequences Are Repurposed for Controlling Antiviral Responses as Non-Retroviral Endogenous Viral Elements 503 510 EN Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/64025 Eukaryotic genomes contain numerous copies of endogenous viral elements (EVEs), most of which are considered endogenous retrovirus (ERV) sequences. Over the past decade, non-retroviral endogenous viral elements (nrEVEs) derived from ancient RNA viruses have been discovered. Several functions have been proposed for these elements, including antiviral defense. This review summarizes the current understanding of nrEVEs derived from RNA viruses, particularly endogenous bornavirus-like elements (EBLs) and endogenous filovirus-like elements (EFLs). EBLs are one of the most extensively studied nrEVEs. The EBL derived from bornavirus nucleoprotein (EBLN) is thought to function as a non-coding RNA or protein that regulates host gene expression or inhibits virus propagation. Ebolavirus and marburgvirus, which are filoviruses, induce severe hemorrhagic fever in humans and nonhuman primates. Although the ecology of filoviruses remains unclear, bats are believed to be potential reservoirs. Based on the knowledge from EBLs, it is postulated that EFLs in the bat genome help to maintain the balance between filovirus infection and the bat’s defense system, which may partially explain why bats act as potential reservoirs. Further research into the functions of nrEVEs could reveal novel antiviral systems and inspire novel antiviral approaches. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Current Insights into Mesenchymal Signatures in Glioblastoma 489 502 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomotsugu Ichikawa Department of Neurological Surgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Review 10.18926/AMO/64024 Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 2055-0936 8 1 2022 Colonization with extended-spectrum beta-lactamase-producing Escherichia coli and traveler's diarrhea attack rates among travelers to India: a systematic review and meta-analysis 22 EN Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Kitahara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayumu Ohno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keinosuke Okamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background India is an attractive destination for travelers. Unfortunately, numerous reports exist on traveler's diarrhea (TD) and fecal colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) among international travelers visiting India. Here, we systematically reviewed studies published on the acquisition of ESBL-EC and TD attack rates among international visitors to India. Methods Design: Systematic review and meta-analysis. A systematic search was performed using Google Scholar, PubMed, EMBASE, Web of Science, and gray literature from 2000 to December 2021, for studies containing data for ESBL-EC acquisition or TD experience related to a trip to India. Random effects models were used to compute the prevalence of ESBL-EC acquisition and TD attack. Results The literature search yielded a total of 5023 records. Of these, 31 met our inclusion criteria for systematic review and only 17 could be meta-analyzed (9 for TD, and 8 for ESBL-EC). The overall pooled attack rate of TD was 39% (95% confidence interval, CI: 25-53%). In studies where travelers' memory was used to diagnose TD, the pooled attack rate of TD was slightly higher (42%, 95% CI: 21-64%) compared to those where TD was objectively documented (33%, 95% CI: 17-49%). There were significant risks to be colonized with ESBL-EC among the travelers who experienced TD. The pooled rate of ESBL-EC colonization was 72% (CI: 67-78%). Most ESBL-EC produced CTX-M-15 enzyme. Furthermore, most of the travelers who acquired ESBL-EC were from highly industrialized countries recruited from travel clinics: Canada (n = 80), Germany (n = 69), Netherlands (n = 20), Sweden (n = 18), Japan (n = 10), Finland (n = 8), USA (n = 7), Spain (n = 5), and Denmark (n = 3). Conclusions TD pooled attack rate and ESBL-EC acquisition among international travelers visiting India were high in this study. However, we cannot make generalizations based upon this TD pooled attack rate for the current situation, due to a lack of current data. Our study highlights that travelers should be advised on TD to ensure that they do not disregard the risk of contracting TD and be better prepared as a result. It also illustrates the importance of international travel in acquiring antibiotic-resistant Escherichia coli. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Effects of Exercise Therapy and Nutrition Therapy on Patients with Possible Malnutrition and Sarcopenia in a Recovery Rehabilitation Ward 423 428 EN Satoshi Takahashi Department of Rehabilitation Medicine, Saiseikai Imabari Daini Hospital Takuya Kushibe Department of Rehabilitation Medicine, Saiseikai Imabari Daini Hospital Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Norio Horiike Department of Internal Medicine, Saiseikai Imabari Daini Hospital Original Article 10.18926/AMO/63901 We compared the effects of an exercise intervention with that of exercise combined with nutrition therapy in patients with possible malnutrition and sarcopenia admitted to a recovery rehabilitation ward, and we examined the differences in the patients’ physical function and activities of daily living (ADLs). There were 16 patients in the Exercise group with exercise therapy and ADL exercises, and 14 patients in the Combined intervention group with exercise therapy, ADL exercises, and nutrition therapy. The survey items were body weight, body mass index, grip strength, lower-leg circumference, gait speed, and ADLs, each of which was measured at the baseline and at 2 weeks, 4 weeks, and at discharge. Significant improvements in grip strength were observed in the Combined intervention group as follows: at 4 weeks>at 2 weeks (p<0.05), and at discharge>baseline and 2 weeks (p<0.05). There were no significant changes in the Exercise group, and an interaction was recognized in both groups. Comprehensive rehabilitation including nutrition therapy is necessary for patients with possible malnutrition and/or sarcopenia, as our results indicate that nutrition therapy in addition to exercise therapy has the effect of promoting improvements of physical function in such patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 5-Nitro-2-(3-phenylpropylamino) Benzoic Acid Inhibits the Proliferation and Migration of Lens Epithelial Cells by Blocking CaMKII Signaling 415 421 EN Haijun Kang Department of Ophthalmology, Suining Central Hospital Dongmei Huang Department of Cardiovascular, Suining Central Hospital Gangjin Kang Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University Xu Yang Department of Ophthalmology, Suining Central Hospital Heng Li Department of Ophthalmology, Suining Central Hospital Siyuan Liu Department of Ophthalmology, Suining Central Hospital Wenjun Gou Department of Ophthalmology, Suining Central Hospital Linglin Liu Department of Ophthalmology, Suining Central Hospital Yuyan Qiu Department of Ophthalmology, Suining Central Hospital Original Article 10.18926/AMO/63896 Posterior capsule opacification (PCO) is a post-surgery complication of cataract surgery, and lens epithelial cells (LECs) are involved in its development. A suppressive effect on LECs is exerted by the non specific chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) exerts. Herein, the growth and migration inhibitory effects of NPPB on LECs were assessed, and the mechanism underlying the effects were investigated by focusing on Ca2+/CaMKII signaling. LECs were treated with different concentrations of NPPB, and the changes in cell viability, cell-cycle distribution, anchorage-dependent growth, migration, Ca2+ level, and CaMKII expression were evaluated. NPPB inhibited LECs’ proliferation and induced G1 cell-cycle arrest in the cells. Regarding LECs’ mobility, NPPB suppressed the cells’ anchorage-dependent growth ability and inhibited their migration. Changes in cell phenotypes were associated with an increased intracellular Ca2+ level and down-regulation of CaMKII. Together these results confirmed the inhibitory effect of NPPB on the proliferation and migration of LECs, and the effect was shown to be associated with the induced level of Ca2+ and the inhibition of CaMKII signaling transduction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Therapeutic Approaches Targeting miRNA in Systemic Lupus Erythematosus 359 371 EN Sumie Hiramatsu-Asano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/63887 Systemic lupus erythematosus (SLE) is a potentially fatal systemic autoimmune disease, and its etiology involves both genetic and environmental factors such as sex hormone imbalance, genetic predisposition, epigenetic regulation, and immunological factors. Dysregulation of microRNA (miRNA) is suggested to be one of the epigenetic factors in SLE. miRNA is a 22-nucleotide single-stranded noncoding RNA that contributes to post-transcriptional modulation of gene expression. miRNA targeting therapy has been suggested to be useful for the treatment of cancers and other diseases. Gene knockout and miRNA targeting therapy have been demonstrated to improve SLE disease activity in mice. However, these approaches have not yet reached the level of clinical application. miRNA targeting therapy is limited by the fact that each miRNA has multiple targets. In addition, the expression of certain miRNAs may differ among cell tissues within a single SLE patient. This limitation can be overcome by targeted delivery and chemical modifications. In the future, further research into miRNA chemical modifications and delivery systems will help us develop novel therapeutic agents for SLE. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 A case of esophageal atresia with the bronchial-like lower esophagus which originates from the left lower lobe bronchus 156 EN Terutaka Tanimoto Department of Pediatric Surgery, Okayama University Hospital Takuo Noda Department of Pediatric Surgery, Okayama University Hospital Reisuke Imaji Department of Pediatric Surgery, Hiroshima City Hiroshima Citizens Hospital Hiroshi Nouso Department of Pediatric Surgery, Okayama University Hospital Background Esophageal atresia with or without a trachea-esophageal fistula occurs due to the failure of separation or incomplete development of the foregut. Therefore, esophageal atresia is often associated with various forms of tracheobronchial anomalies. We report an extremely rare case of esophageal atresia. Case presentation A female infant was born at 37 weeks of gestation and weighed 2596 g. A diagnosis of esophageal atresia and total anomalous pulmonary vein return type III were confirmed. The infant had respiratory distress that required tracheal intubation and ventilatory support soon after birth. Temporary banding of the gastroesophageal junction and gastrostomy were performed on the second day of life. However, her respiratory condition deteriorated due to atelectasis of the left lung and compensatory hyperinflation of the right lung. Preoperative examinations showed the unilobe and atelectatic left lung. The trachea was trifurcated in three directions, and the branch that was expected to be the left main bronchus was blind-ended. The dorsal branch was cartilaginous and bifurcated into the left lower lobe bronchus and lower esophagus approximately 1 cm distal from the tracheal trifurcation. The cartilaginous tissue continued to the lower esophagus. The diagnosis of esophageal atresia with the lower esophagus which originated from the left lower lobe bronchus was made. Esophageal atresia repair was performed when the patient was 4 months of age. The esophagus was dissected distally to the bifurcation of the left lower lobe bronchus via right thoracotomy. The lower esophagus was bronchial-like in appearance, transitioning to the normal esophageal wall approximately 7 mm distal to the transected edge. The cartilage tissue was completely resected during surgery, and a primary end-to-end anastomosis of the esophagus was successfully performed. Histopathological findings revealed that the extracted specimen was surrounded by tracheal cartilage and that the inner surface was covered by stratified squamous epithelium that originated from the esophagus. Conclusions In cases of esophageal atresia with an atypical clinical presentation, there may be unique structural abnormalities of the foregut. We emphasize the importance of a preoperative surgical planning since an inadequate operation can lead to fatal complications. No potential conflict of interest relevant to this article was reported.

Japanese Circulation Society Acta Medica Okayama 1346-9843 86 8 2022 Overview of the 86th Annual Scientific Meeting of the Japanese Circulation Society　― Cardiology Spreading Its Wings ― 1312 1318 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masatoki Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumi Yokohama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makiko Taniyama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teiji Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The 86th Annual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 11 2021 Cholera Rapid Diagnostic Tests for the Detection of Vibrio cholerae O1: An Updated Meta-Analysis 2095 EN Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Kitahara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayumu Ohno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anusuya Debnath Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keinosuke Okamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The rapid diagnosis of cholera contributes to adequate outbreak management. This meta-analysis assesses the diagnostic accuracy of cholera rapid tests (RDTs) to detect Vibrio cholerae O1. Methods: Systematic review and meta-analysis. We searched four databases (Medline, EMBASE, Google Scholar, and Web of Science up to 8 September 2021) for studies that evaluated cholera RDTs for the detection of V. cholerae O1 compared with either stool culture or polymerase chain reaction (PCR). We assessed the studies' quality using the QUADAS-2 criteria. In addition, in this update, GRADE approach was used to rate the overall certainty of the evidence. We performed a bivariate random-effects meta-analysis to calculate the pooled sensitivity and specificity of cholera RDTs. Results: Overall, 20 studies were included in this meta-analysis. Studies were from Africa (n = 11), Asia (n = 7), and America (Haiti; n = 2). They evaluated eight RDTs (Crystal VC-O1, Crystal VC, Cholkit, Institut Pasteur cholera dipstick, SD Bioline, Artron, Cholera Smart O1, and Smart II Cholera O1). Using direct specimen testing, sensitivity and specificity of RDTs were 90% (95% CI, 86 to 93) and 86% (95% CI, 81 to 90), respectively. Cholera Sensitivity was higher in studies conducted in Africa [92% (95% CI, 89 to 94)] compared with Asia [82% (95% CI, 77 to 87)]. However, specificity [83% (95% CI, 71 to 91)] was lower in Africa compared with Asia [90% (95% CI, 84 to 94)]. GRADE quality of evidence was estimated as moderate. Conclusions: Against culture or PCR, current cholera RDTs have moderate sensitivity and specificity for detecting Vibrio cholerae O1. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 10 7 2022 The Effectiveness of Pre-Operative Screening Tests in Determining Viral Infections in Patients Undergoing Oral and Maxillofacial Surgery 1348 EN Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuka Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuaki Hasegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Ai Fujimura Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Ayaka Fujisawa Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumika Mukainaka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiko Furuki Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8, $905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 Verrucous carcinoma of the esophagus with complete response after chemoradiotherapy 128 EN Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Sakurama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background : Verrucous carcinoma of the esophagus (VCE) is a rare tumor that is difficult to diagnose. In most cases, biopsies show nonspecific inflammatory and hyperkeratotic changes and do not show malignant findings. Most VCEs are slowly growing, locally advanced tumors with few metastases. Treatments for VCE are the same as for normal esophageal cancer, involving combined chemotherapy, surgical resection, and radiation therapy. However, it has been reported that VCE has a poor response to radiation or chemoradiotherapy (CRT). A case of VCE with complete response (CR) after CRT is presented. Case presentation : A 70-year-old man was found to have white, irregular esophageal mucosa 4 years earlier. He had been followed up as an outpatient as having candidal esophagitis. However, his tumor grew gradually, and biopsy was performed by endoscopic mucosal resection (EMR). He was finally diagnosed with VCE. He had no metastases to distant organs, but some lymph node metastases were suspected. The tumor invaded his left bronchus. The esophagostomy and gastrostomy were constructed as emergent procedures. The patient then underwent definitive CRT. 4 weeks after the end of CRT, two-stage esophagectomy was performed. First, he underwent esophagectomy with thoracic lymph node dissection. A latissimus dorsi flap was patched to the bronchus after primary suture of the hole. 6 weeks later, reconstruction of the gastric tube was performed through the antethoracic route. The pathological findings showed CR to CRT, with no proliferative cancer cells in the specimen. The patient has had no recurrence for three and half years after the resection. Conclusions : We presented a locally advanced VCE that achieved CR to CRT. In cases that have some difficulty for local resection, CRT might be an appropriate treatment for VCE. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1660-4601 19 12 2022 Long-Term Kinetics of Serological Antibodies against Vibrio cholerae Following a Clinical Cholera Case: A Systematic Review and Meta-Analysis 7141 EN Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kei Kitahara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Debmalya Mitra Collaborative Research Center of Okayama University for Infectious Diseases in India Ayumu Ohno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still limited. Several studies have reported the duration of antibodies following cholera; however, systematic reviews including a quantitative synthesis are lacking. Objective: To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case. Methods: Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against Vibrio cholerae in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged >= 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included. Results: Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged >= 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis. Conclusions: This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Evaluation of Fast Diffusion Kurtosis Imaging Using New Software Designed for Widespread Clinical Use 297 305 EN Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Konishi Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Yuuki Yoshimura Radiological Technology, Graduate School of Health Sciences, Okayama University Kentaro Hamada Radiological Technology, Graduate School of Health Sciences, Okayama University Abdullah Khasawnehc Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Majd Barham Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nouha Tekiki Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Irfan Sugianto Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Babatunde O. Bamgbose Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hinata Ishizaka Radiological Technology, Graduate School of Health Sciences, Okayama University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Akira Kurozumi Central Division of Radiology, Okayama University Hospital Toshi Matsushita Central Division of Radiology, Okayama University Hospital Seiichiro Ohno Central Division of Radiology, Okayama University Hospital Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Asaumi Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63739 Clinical research using restricted diffusion-weighted imaging, especially diffusion kurtosis (DK) imaging, has been progressing, with reports on its effectiveness in the diagnostic imaging of cerebral infarctions, neurodegenerative diseases, and tumors, among others. However, the application of DK imaging in daily clinical practice has not spread because of the long imaging time required and the use of specific software for image creation. Herein, with the aim of promoting clinical research using DK imaging at any medical facility, we evaluated fast DK imaging using a new software program. We developed a new macro program that produces DK images using general-purpose, inexpensive software (Microsoft Excel and ImageJ), and we evaluated fast DK imaging using bio-phantoms and a healthy volunteer in clinical trials. The DK images created by the new software with diffusion-weighted images captured with short-time imaging sequences were similar to the original DK images captured with long-time imaging sequences. The DK images using three b-values, which can reduce the imaging time by 43%, were equivalent to the DK images using five b-values. The DK imaging technique developed herein might allow any medical facility to increase its daily clinical use of DK imaging and easily conduct clinical research. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0735-6757 58 2022 Mid-term (30- to 90-day) neurological changes in out-of-hospital cardiac arrest patients: A nationwide retrospective study (the JAAM-OHCA registry) 27 32 EN Hiromichi Naito Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Tsuyoshi Nojima Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Takashi Yorifuji Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Epidemiology Noritomo Fujisaki Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Atsunori Nakao Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Emergency, Critical Care, and Disaster Medicine Objective Few studies have focused on mid/long-term neurological changes in out-of- hospital cardiac arrest (OHCA) survivors. Some studies suggest that there is still a slow, small, progressive improvement in cognitive function and quality of life for this population, even in the mid/long term. However, clinical data focused on mid/long-term outcomes for OHCA patients are still lacking. This study aimed to assess mid-term neurological changes in OHCA patients. We summarized patients' improved or worsened neurological changes between 30 and 90 days. Then we identified the relationship between clinical variables and 30- to 90-day neurological improvement. Methods A retrospective review of data (Jun 2014 - Dec 2017) from a Japanese nationwide OHCA registry was conducted. Inclusion criteria were OHCA patients ≥18 years old. Exclusion criteria were death within 30 days and missing Cerebral Performance Category (CPC) score at 30 and 90 days. We described the distributions of 30-day and 90-day CPC scores as well as the number and portion of patients whose CPC scores improved and worsened between 30 and 90 days. Additionally, factors affecting improved neurological changes over the time period were examined using multivariable logistic regression. Results Of the registry's 34,745 patients, 1868 were analyzed. Favorable neurological outcomes (CPC scores of 1 and 2) were seen in 1020/1868 patients at 90 days. CPC scores at 90 days were: CPC 1: 866 (46%), CPC 2: 154 (8.2%), CPC 3: 224 (12%), and CPC 4: 392 (20%), respectively. A total of 232 patients (CPC 5: 12%) died between 30 and 90 days. In 133 patients (7%), 90-day CPC scores improved compared to their 30-day scores. In 260 patients (14%), 90-day CPC scores worsened compared with their 30-day scores. Application of target temperature management was an independent factor for 30- to 90-day neurological improvement (adjusted odds ratio: 1.69, 95% confidence interval: 1.07–2.68). Conclusions In our nationwide registry, 7% of resuscitated patients had improved neurological changes in the 30- to 90-day period; most of the improvements were CPC scores improving from 2 to 1. Target temperature management was an independent factor associated with CPC improvement over the 30- to 90-day period. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Possibility of Predicting Pelvic Inclination Following Total Hip Arthroplasty Based on the Preoperative State: Sacral Slope and Pelvic Incidence Minus Lumbar Lordosis as Predictive Factors 273 280 EN Shuro Furuichi Department of Bone and Joint Surgery, Kawasaki Medical School Shigeru Mitani Department of Bone and Joint Surgery, Kawasaki Medical School Hirosuke Endo Department of Bone and Joint Surgery, Kawasaki Medical School Yoshifumi Namba Department of Bone and Joint Surgery, Kawasaki Medical School Toyohiro Kawamoto Department of Bone and Joint Surgery, Kawasaki Medical School Original Article 10.18926/AMO/63721 Following total hip arthroplasty (THA), some patients exhibit anterior or posterior pelvic tilt (PT). This case– control study investigated whether changes to PT following THA can be preoperatively predicted. Methods: 135 patients with hip osteoarthritis who underwent THA were assessed. The parameters measured preoperatively and one year postoperatively were lumbar lordosis (LL) based on plain X-ray and pelvic incidence (PI), PT, and sacral slope (SS), all of which were measured as pelvic morphological angles. Patients were classified into groups (A–E) based on the degree of post-THA PT, and their preoperative conditions were compared. PI minus LL was used to evaluate spinal alignment and pelvic balance. Results: Overall, 33%, 30%, 21%, 13%, and 3% of the hips of patients in Groups A, B, C, D, and E were postoperatively assessed. In Groups A–E, the SS values were 34.6°±8.9°, 37.6°±8.4°, 37.9°±8.9°, 42.6°±9.5°, and 60.0°±11.1°, whereas the PI minus LL values were 2.9°±15.0°, 1.2°±13.6°, 3.6°±17.7°, 12.7°±13.1°, and －1.3°±11.7°, respectively. Conclusions: Following THA, 70% of patients experienced posterior PT. Pre-THA SS ≥45° or PI minus LL ≥15° signified marked postoperative posterior tilt and could predict postoperative PT following THA. These findings are useful for implant placement, as they can predict pelvic inclination. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2407 22 1 2022 Optimal surveillance of intraductal papillary mucinous neoplasms of the pancreas focusing on remnant pancreas recurrence after surgical resection 588 EN Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Background The international consensus guidelines for intraductal papillary mucinous neoplasm of the pancreas (IPMN) presented clinical features as indications for surgery. Whereas surveillance for recurrence, including de novo lesions, is essential, optimal surveillance protocols have not been established. Aim and methods This study aimed to assess the clinical features of recurrence at the remnant pancreas (Rem-Panc) and extra-pancreas (Ex-Panc) after surgery for IPMN. Ninety-one patients of IPMN that underwent detailed preoperative assessment and pancreatectomy were retrospectively analyzed, focusing especially on the type of recurrence. Results The IPMNs were finally diagnosed as low-grade dysplasia (LDA, n = 42), high-grade dysplasia (HAD, n = 19), and invasive carcinoma (IPMC, n = 30). Recurrence was observed in 26 patients (29%), of which recurrence was seen at Rem-Panc in 19 patients (21%) and Ex-Panc in 7 patients (8%). The frequency of Rem-Panc recurrence was 10% in LDA, 21% in HDA, and 37% in IPMC. On the other hand, Ex-Panc recurrence was observed only in IPMC (23%). Ex-Panc recurrence showed shorter median recurrence-free survival (RFS) and overall survival (OS) than Rem-Panc recurrence (median RFS 8 months vs. 35 months, p < 0.001; median OS 25 months vs. 72 months, p < 0.001). Regarding treatment for Rem-Panc recurrence, repeat pancreatectomy resulted in better OS than no repeat pancreatectomy (MST 36 months vs. 15.5 months, p = 0.033). On multivariate analysis, main duct stenosis or disruption as a preoperative feature (hazard ratio [HR] 10.6, p = 0.002) and positive surgical margin (HR 4.4, p = 0.018) were identified as risk factors for Rem-Panc recurrence. Conclusions The risk factors for Rem-Panc and Ex-Panc recurrence differ. Therefore, optimal surveillance on these features is desirable to ensure that repeat pancreatectomy for Rem-Panc recurrence can be an appropriate surgical intervention. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Retrospective Cohort Study of Clinical Efficacy and Safety of Cefozopran for Treating Febrile Neutropenia during Chemotherapy in Patients with Lung Cancer 167 172 EN Tsukasa Higashionna Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Satoru Esumi Department of Pharmacy, Okayama University Hospital Kiminaka Murakawa Department of Pharmacy, Okayama University Hospital Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Toshiaki Sendo Department of Pharmacy, Okayama University Hospital Original Article 10.18926/AMO/63410 Febrile neutropenia (FN) is a serious side effect in patients undergoing cancer chemotherapy and frequently proves fatal. Since infection control is crucial in the management of FN, the antimicrobial agent cefozopran (CZOP) has been recommended but not approved for routine use in clinical care of FN in Japan. However, few studies of CZOP in the management of FN have used a thrice daily dose schedule. The aim of this study was to retrospectively compare the efficacy and safety of CZOP at a dose of 1 g three times daily to those of cefepime (CFPM) in the treatment of FN in our lung cancer patients. The response rates of the CZOP and CFPM groups were 89.5% (17/19 cases) and 83.0% (39/47 cases), respectively, with no significant difference between the two groups. The median duration of antimicrobial treatment was 6 days (4-10 days) in the CZOP group and 7 days (3-13 days) in the CFPM group, with no significant difference between groups. The incidence rates of adverse events were 21.1% (4/19 cases) in the CZOP group and 19.1% (9/47 cases) in the CFPM group. No adverse events of Grade 3 or higher were observed in either group. The findings of the present study suggest that CZOP administration at a dose of 1 g three times per day as an antimicrobial treatment alternative against FN. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Clinicopathological Features and Surgical Outcomes of Small Bowel Metastasis from Renal Cell Carcinoma 155 165 EN Jiro Kimura Department of Gastroenterological Surgery, National Center for Global Health and Medicine Takehiro Okabayashi Department of Gastroenterological Surgery, National Center for Global Health and Medicine Kenta Sui Department of Gastroenterological Surgery, National Center for Global Health and Medicine Motoyasu Tabuchi Department of Gastroenterological Surgery, National Center for Global Health and Medicine Jun Iwata Department of Diagnostic Pathology, National Center for Global Health and Medicine Yasuhiro Hata Department of Radiology, National Center for Global Health and Medicine Tatsuo Iiyama Department of Biostatistics, National Center for Global Health and Medicine Noriaki Ono Department of Urology, Kochi Health Sciences Center Original Article 10.18926/AMO/63409 Small bowel metastasis from renal cell carcinoma (RCC) is rare, and its clinicopathological characteristics are unclear; thus, we revisited the concept of this tumor and reviewed its diagnostic and treatment modalities. We filtered MEDLINE searches of articles published in English between 1950 and 2019, and identified 100 patients who had undergone treatment, including 1 patient from our clinic. We extracted patient characteristics, treatment, and prognostic data, resulting in clinicopathological data on 100 patients (83 men, 17 women). Mean age was 63 years (range, 16-86 years). Tumor sites were duodenum, jejunum, ileum, and multiple sites in 30, 37, 25, and 7 patients, respectively. The 1-, 3-, and 5-year overall survival rates after diagnosis were 53.0%, 36.0%, and 36.0%. Curative resection patients showed 62.1% 5-year survival after surgery, vs. 27.5% in noncurative surgical management cases. Good prognoses can be expected if these tumors are identified early for complete removal. Surgery is the only curative option. To determine the best management strategy and improve prognostic accuracy, we continue to collect and analyze epidemiological and pathological data. Although this condition is rare, surgery should be considered if curative resection is expected. Prognosis after curative resection is not poor, but recurrence is not unlikely. No potential conflict of interest relevant to this article was reported.

岡山大学全学教育・学生支援機構 Acta Medica Okayama 2432-9665 6 2021 コロナ禍における「オンラインにほんごカフェ」の意義ー参加者及びスタッフの視点からー 67 86 EN Tomomi Moriya Masumi Nagano 10.18926/63331 本稿は、コロナ禍において対面からオンラインヘと実施形態を変更して開催することとなった正課外での多文化間交流を目的とした「にほんごカフェ」の活動が、参加者及びスタッフにとってどのように意義づけられていたのかを明らかにした上で、今後の活動のあり方を検討することを目的とする。2021年8月に行ったインタビュー調査の結果、「オンラインにほんごカフェ」が参加者とスタッフの双方にとっての多文化間交流機会かつ雑談の機会であり、非母語話者にとっての日本語使用機会として意義づけられていることが明らかとなった。一方で、多人数でのコミュニケーションの困難さや活動外への関係性の発展の難しさ等、オンライン特有の課題も見られた。 No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3484 57 3 2022 Association between serum miRNAs and gingival gene expression in an obese rat model 502 509 EN Takayuki Maruyama Department of Preventive Dentistry, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Terumasa Kobayashi Department of Preventive Dentistry, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Sugiura Department of Preventive Dentistry, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Toshiki Yoneda Department of Preventive Dentistry, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ekuni Department of Preventive Dentistry, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Manabu Morita Department of Preventive Dentistry, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Introduction Recent studies have reported a relationship between periodontitis and obesity; however, the mechanisms of obesity’s effects on periodontitis are not well understood. On the other hand, microRNAs (miRNAs) are known to play key roles in the post-transcriptional regulation gene expression by suppressing translation and protein synthesis. We examined the association between obesity-related miRNAs and gene expression in gingival tissue using miRNA–messenger RNA (mRNA) pairing analysis in an obese rat model. Methods Sixteen male Wistar rats aged 8 weeks old were divided into two groups: the control group was fed a normal powdered food for 8 weeks, and the obesity group was fed a high-fat diet for 8 weeks. Distance from the cement–enamel junction to the alveolar bone crest of the first molars was measured. miRNA microarray analysis was performed on samples of serum and gingival tissue; the resulting data were used to calculate fold changes in miRNA levels in the obesity group relative to the control group, and miRNA–mRNA pairing analysis was performed to identify mRNAs potentially targeted by miRNAs of interest. Results Alveolar bone loss in the obesity group exceeded that in the control group (p = .017). miRNA–mRNA pairing analysis identified an association between 4 miRNAs (miR-759, miR-9a-3p, miR-203b-3p, and miR-878) that were differentially expressed in the obesity and control groups and 7 genes (Ly86, Arid5b, Rgs18, Mlana, P2ry13, Kif1b, and Myt1) expressed in gingival tissue. Conclusion This study revealed that several miRNAs play an important role in the mechanism of periodontal disease progression induced by the obesity. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 8 1 2022 Surgical resection of mixed neuroendocrine-non-neuroendocrine neoplasm in the biliary system: a report of two cases 38 EN Ayano Tamaki Center for Graduate Medical Education, Okayama University Hospital Yuma Tani Department of Gastroenterological Surgery, Okayama University Hospital Hiroki Sato Department of Gastroenterological Surgery, Okayama University Hospital Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Hospital Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Takashi Kuise Department of Gastroenterological Surgery, Okayama University Hospital Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Hospital Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Hospital Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Hospital Kenjiro Kumano Department of Gastroenterological Surgery, Okayama University Hospital Kosei Takagi Department of Gastroenterological Surgery, Okayama University Hospital Takahito Yagi Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Background Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. Case presentation Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. Conclusion We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1868-4483 7 2 2016 Thrombolysis with Low-Dose Tissue Plasminogen Activator 3–4.5 h After Acute Ischemic Stroke in Five Hospital Groups in Japan 111 119 EN Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Syoichiro Kono Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Yasuyuki Ohta epartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita epartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Deguchi epartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Manabe Okayama National Hospital Medical Center Yoshiki Takao Okayama National Hospital Medical Center Kenichi Kashihara Okayama National Hospital Medical Center Satoshi Inoue Okayama National Hospital Medical Center Hideki Kiriyama Okayama National Hospital Medical Center Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3-4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3-4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3-4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3-4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0-1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3-4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 C-arm Free O-arm Navigated Posterior Atlantoaxial Fixation in Down Syndrome: A Technical Note 71 78 EN Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Sumeet Sonawane Department of Orthopaedic Surgery, Okayama Rosai Hospital Yoshihiro Fujiwara Department of Orthopaedic Surgery, Okayama Rosai Hospital Koji Uotani Department of Orthopaedic Surgery, Okayama Rosai Hospital Shinya Arataki Department of Orthopaedic Surgery, Okayama Rosai Hospital Taro Yamauchi Department of Orthopaedic Surgery, Okayama Rosai Hospital Youchen Ye Department of Orthopaedic Surgery, Okayama Rosai Hospital Haruo Misawa Department of Orthopaedic Surgery, Okayama University Hospital Case Report 10.18926/AMO/63214 The surgical treatment of pediatric atlantoaxial subluxation (AAS) in Down syndrome (DS) remains technically challenging due to radiation exposure and complications such as vertebral artery injury and nonunion. The established treatment is fixation with a C1 lateral mass screw and C2 pedicle screw (modified Goel technique). However, this technique requires fluoroscopy for C1 screw insertion. To avoid exposing the operating team to radiation we present here a new C-arm free O-arm navigated surgical procedure for pediatric AAS in DS. A 5-year-old male DS patient had neck pain and unsteady gait. Radiograms showed AAS with an atlantodental interval of 10 mm, and irreducible subluxation on extension. CT scan showed Os odontoideum and AAS. MRI demonstrated spinal cord compression between the C1 posterior arch and odontoid process. We performed a C-arm free O-arm navigated modified Goel procedure with postoperative halo-vest immobilization. At oneyear follow-up, good neurological recovery and solid bone fusion were observed. The patient had no complications such as epidural hematoma, infection, or nerve or vessel injury. This novel procedure is a useful and safe technique that protects surgeons and staff from radiation risk. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 In Vivo Microwave Ablation of Normal Swine Lung at High-power, Short-duration Settings 57 62 EN Toshihiro Iguchi Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Matsui Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Toji Department of Pathology, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Tomita Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Komaki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Umakoshi Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63212 To evaluate the volume and heat-sink effects of microwave ablation (MWA) in the ablation zone of the normal swine lung. MWA at 100 W was performed for 1, 2, and 3 min in 7, 5, and 5 lung zones, respectively. We assessed the histopathology in the ablation zones and other outcome measures: namely, length of the longest long and short axes, sphericity, ellipsoid area, and ellipsoid volume. The mean long- and short-axis diameters were 22.0 and 14.1 mm in the 1-min ablation zone, 27.6 and 20.2 mm in the 2-min ablation zone; and 29.2 and 21.2 mm in the 3-min ablation zone, respectively. All measures, except sphericity, were significantly less with 1-min ablation than with either 2- or 3-min ablation. There were no significant differences between the 2- and 3-min ablation zones, but all measures except sphericity were larger with 3-min ablation. Although there were no blood vessels that resulted in a heat-sink effect within the ablation zones, the presence of bronchi nearby in 5 lung ablation zones resulted in reduced ablation size. In high-power, short-duration MWA, the lung ablation volume was affected by ablation time. Some ablations showed that a heat-sink effect by a neighboring bronchus might occur. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Obesity’s Influence on Insulin Resistance in Pregnant Women with Polycystic Ovary Syndrome 51 56 EN Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hayata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63209 Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disorder that is associated with high insulin resistance and obesity. However, ~70% of women with PCOS in Japan are non-obese. We retrospectively analyzed the cases of 163 Japanese women with PCOS who visited our Ob/Gyn department in 2006-2018 to determine which has a greater effect on insulin resistance: PCOS or obesity. We reviewed the women’s medical records and calculated their insulin resistance and insulin secretion. The women’s mean age and pre-pregnancy body mass index (BMI) were 30±5.8 years and 24.8±5.6 kg/m2, respectively; their mean ± SD fasting plasma glucose, 94.1±13.7 mg/dL; HOMA-IR, 2.1±2.0; QUICKI, 0.4±0.0; and HOMA-β, 108.9±88.0%. Sixtyeight women were pregnant, and 37% (n=25) were obese (BMI ≥ 25 kg/m2). Obesity had a greater effect on insulin resistance: fasting plasma glucose F(1, 53)=6.134, p<0.05; fasting insulin F(1, 53)=31.606, p<0.01; HOMA-IR F(1, 53)=31.670, p<0.01; QUICKI F(1, 53)=16.156, p<0.01. There was no significant difference in values other than QUICKI and testosterone between the women with and without PCOS. Obesity thus had a greater effect on increased insulin resistance in pregnant women with PCOS. Further studies of the insulin resistance of non-obese women with PCOS is needed, as non-obese women with PCOS are common in Asia. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 16 8 2021 Clinical and phenotypical characteristics of submucosal invasive carcinoma in non-ampullary duodenal cancer e0256797 EN Katsunori Matsueda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Masahiro Nakagawa Department of Endoscopy, Hiroshima City Hiroshima Citizens Hospital Kazuhiro Matsueda Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital Tomohiro Toji Department of Diagnostic Pathology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Hepato-Biliary-Pancreatic Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective The rare incidence of submucosal invasive non-ampullary duodenal carcinoma has led to scant information in literature; therefore, we compared the clinicopathological features between submucosal invasive carcinoma (SM-Ca), mucosal carcinoma (M-Ca), and advanced carcinoma (Ad-Ca). Materials We retrospectively analyzed 165 patients with sporadic non-ampullary duodenal carcinomas (SNADCs) from four institutions between January 2003 and December 2018. The SNADCs were divided to three groups according to histological diagnosis: SM-Ca, M-Ca, and Ad-Ca. The clinicopathological characteristics and mucin phenotypes were compared between groups. Results Among the 165 SNADCs, 11 (7%) were classified as SM-Ca, 70 (42%) as M-Ca, and 84 (51%) as Ad-Ca. We found that all SM-Ca (P = 0.013) and most Ad-Ca (P = 0.020) lesions were located on the oral-Vater; however, an almost equal distribution of M-Ca lesions was found between the oral- and anal-Vater. No significant difference was observed between the tumor diameter of M-Ca and SM-Ca; however, 45% (5/11) of SM-Ca were <= 10 mm. A total of 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were classified as intestinal phenotype; whereas most M-Ca were classified as intestinal phenotype (67%, 8/12). Conclusions SM-Ca lesions were all located on the oral-Vater and were highly associated with the gastric mucin phenotype, which were different from the features of most M-Ca. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Plasma Concentrations of Trace Elements Selenium and Cobalt During and After Coronary Artery Bypass Grafting Surgery 33 39 EN Jia-Yi Zhou The Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Hai-Tao Hou Unit of Perfusion, Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospita Shi-Fu Wang Unit of Perfusion, Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Qin Yang The Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Guo-Wei He The Institute of Cardiovascular Diseases & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Original Article 10.18926/AMO/63206 Trace elements selenium (Se) and cobalt (Co) are essential in the human body, and a correlation between Se and cardiac surgery has been suggested. We investigated the plasma concentrations of Se and Co during and after coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB). From December 2019 to January 2020, preoperative plasma samples from isolated first-time CABG patients (n=20; 10 males, 10 females) were prospectively collected post-anesthesia and before CPB (T1), 45 min after CPB started (T2), 90 min after CPB started (T3), and postoperative days 1 (T4), and day 4 (T5). The plasma concentrations of Se and Co were measured. The Se concentration was significantly decreased at T2 (105.24±4.08 vs. 68.56±2.42 μg/L, p<0.001) and T3 (105.24±4.08 vs. 80.41±3.40 μg/L, p<0.001). The Co concentration was significantly decreased at T4 (0.35±0.19 vs. 0.26±0.13 μg/L, p<0.01) and T5 (0.35±0.19 vs. 0.23±0.11 μg/L, p<0.001). Five patients developed atrial fibrillation (AF); there was no other operative mortality or major morbidity. This is the first report of alterations of plasma Se and Co concentrations during and after CABG surgery. Our results may indicate that Se supplementation before or during CABG and Co supplementation after CABG may become necessary for patients undergoing CABG. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Mouse Model for Optogenetic Genome Engineering 1 5 EN Tomoka Takao Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Yamada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Takarada Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/63202 Optogenetics, a technology to manipulate biological phenomena thorough light, has attracted much attention in neuroscience. Recently, the Magnet System, a photo-inducible protein dimerization system which can control the intracellular behavior of various biomolecules with high accuracy using light was developed. Furthermore, photoactivation systems for controlling biological phenomena are being developed by combining this technique with genome-editing technology (CRISPR/Cas9 System) or DNA recombination technology (Cre-loxP system). Herein, we review the history of optogenetics and the latest Magnet System technology and introduce our recently developed photoactivatable Cre knock-in mice with temporal-, spatial-, and cell-specific accuracy. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2296-634X 9 2022 Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish 694018 EN Genta Takemoto Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Masaki Matsushita Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Takaaki Okamoto Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine Toshinari Ito Division of Molecular Therapeutics, Aichi Cancer Center Research Institute Yuki Matsuura Division of Molecular Therapeutics, Aichi Cancer Center Research Institute Chieko Takashima Division of Molecular Therapeutics, Aichi Cancer Center Research Institute Toyofumi Fengshi Chen-Yoshikawa Department of Thoracic Surgery, Nagoya University Graduate School of Medicine Hiromichi Ebi Division of Molecular Therapeutics, Aichi Cancer Center Research Institute Shiro Imagama Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine Hiroshi Kitoh Department of Orthopaedic Surgery, Aichi Children’s Health and Medical Center Kinji Ohno Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine Yasuyuki Hosono Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones. No potential conflict of interest relevant to this article was reported.

Wiley Periodicals, Inc Acta Medica Okayama 2055-5822 2022 2022 Assessment of congestion and clinical outcomes in patients with chronic heart failure using shear wave elasticity EN Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rika Takemoto Division of Medical Support, Okayama University Hospital Norihisa Toh Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims The relief of congestion is essential for the prevention of worsening heart failure (HF) resulting in hospitalizations. Assessment of the degree of organ congestion in the chronic phase of HF is important for determining therapeutic strategies. The aim of this study was to evaluate the efficacy of shear wave (SW) elasticity for assessing congestion and clinical outcomes in patients with chronic HF. Methods and results We prospectively enrolled 345 consecutive patients with chronic HF who underwent SW elastography at outpatient clinic. Patients were divided into two groups according to the median value of SW elasticity: low group (SW elasticity <6.4 kPa, n = 176) and high group (SW elasticity >= 6.4 kPa, n = 169). The endpoint was cardiovascular death or hospitalization for HF. During the median follow-up period of 19 months (range: 7-36 months), cardiovascular death or hospitalization for HF occurred in 4 patients of low group and 27 patients of high group. In high group, 8 patients died, and 19 patients were hospitalized for HF. In low group, 3 patients died, and 1 patient was hospitalized. Kaplan-Meier analysis showed that the event-free survival rate was worse in high group than in low group (log-rank test, P = 0.004). After adjusting for variables, high SW elasticity was independently related to cardiac events. In multivariate regression analysis, SW elasticity was correlated with left atrial volume index, early diastolic mitral inflow velocity to mitral annular velocity ratio, and inferior vena cava diameter. Conclusions The SW elasticity reflected haemodynamic congestion in patients with chronic HF, which was related to cardiac events. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 11 12 2021 Bilateral Optic Disc Swelling as a Plausible Common Ocular Sign of Autoinflammatory Diseases: Report of Three Patients with Blau Syndrome or Cryopyrin-Associated Periodic Syndrome 1433 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masato Yashiro Department of Ophthalmology, Okayama University Hospital Osamu Yamasaki Melanoma Center, Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akira Manki Department of Pediatrics, Okayama City Hospital The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Morphological Changes and Durability of Skin and Mucosal Flaps in Intraoral and Pharyngeal Reconstructions: Long-term Follow-up and Literature Review for Potential Second Carcinomas 725 734 EN Hiroshi Matsumoto Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Ota Department of Plastic and Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Narushi Sugiyama Department of Plastic and Reconstructive Surgery, Japanese Red Cross Okayama Hospital Satoshi Onoda Department of Plastic and Reconstructive Surgery, Kagawa Rosai Hospital Takuma Makino Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiko Takeda Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Nobuyoshi Mizukawa Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital Original Article 10.18926/AMO/62813 The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify the morphological changes, long-term durability, and potential for secondary carcinogenesis in such tissues. In our single-center study, the rough morphological changes in 54 cases of intraoral and pharyngeal skin and mucosal flaps were evaluated more than 10 years after flap transfer. In addition, the literature on the development of second carcinomas from skin flaps was reviewed. The mean follow-up period for transferred flaps was 148 months. The reconstruction areas and the probability of morphological changes were significantly correlated (p=0.006), especially in cases with tongue, lower gingiva, and buccal mucosal reconstruction. Free jejunal flap surfaces were well maintained, whereas tubed skin flaps showed severe morphological changes in cases with pharyngeal reconstruction. None of the flaps in our series developed second primary carcinomas. Skin flaps generally had good durability for > 10 years in intraoral environments, while mucosal flaps had better durability for pharyngeal reconstruction. Second squamous carcinomas arising from skin flaps are extremely rare; however, surgeons should take this possibility into consideration and conduct meticulous and long-term follow-up. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis 705 711 EN Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62810 Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients’ prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 The Effect of Peer Instruction Lectures on Learning Attitudes in Epidemiology Education 601 609 EN Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Original Article 10.18926/AMO/62773 Research suggests that the fundamental concepts of epidemiology cannot be sufficiently learned in traditional lectures, and interactive learning is necessary. However, few studies have investigated interactive epidemiology education in general, or peer instruction (PI) in particular. This study investigated the effect of PI. Study par-ticipants were fourth-year medical students. The attitude of participants in regard to PI learning was examined in a non-PI and a PI group. The Survey of Attitudes Toward Statistics (SATS) (containing six sub-categories) was conducted as a learning-attitudes index. The pre- and post-lecture scores were compared between the non-PI and PI groups using double robust (DR) estimation. The non-PI and PI groups consisted of 20 and 121 student participants, respectively. In DR estimation, affect exhibited the lowest SATS score changes, at －0.51 (95% confidence interval －0.78 to －0.24; p-value < 0.001), whereas effort exhibited the highest score changes of 0.01 (95% confidence interval －0.30 to 0.32; p-value = 0.952). The epidemiology lecture with PI did not increase the SATS scores. This might be due to issues related to the experimental design. Further research investigating the effects of interactive epidemiology education, it will be necessary to develop tools for assessing the learning of epidemiological concepts and to improve the research design. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Factors for Acute Kidney Injury Following Total Arch Replacement and Association with Temperature Management During Cardiopulmonary Bypass: A Single-center Retrospective Observational Study 585 593 EN Hiroki Omiya Department of Anesthesiology and Critical Care Medicine, Hiroshima Citizens Hospital Makoto Takatori Department of Anesthesiology and Critical Care Medicine, Hiroshima Citizens Hospital Keiji Yunoki Department of Cardiovascular Surgery, Hiroshima Citizens Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitation, Okayama University Hospital Original Article 10.18926/AMO/62771 Many patients develop acute kidney injury (AKI) after vascular surgery. In this retrospective observational study, we investigated the risk factors for AKI defined using the Kidney Disease Improving Global Outcomes criteria after total arch replacement (TAR). Additionally, we investigated the influence of temperature manage-ment during cardiopulmonary bypass (CPB) on postoperative renal function by propensity score-matched anal-ysis. We retrospectively analyzed 161 consecutive patients who underwent TAR between 2016 and 2019. Postoperative AKI occurred in 48.7% of the patients. In the multivariate analysis, male sex (odds ratio [OR] 3.95, 95% confidence interval [95%CI] 1.56-8.27, p = 0.002), ACE inhibitors/ARB medication (OR 3.19, 95%CI 1.49-6.82, p = 0.003), preoperative chronic kidney disease (OR 2.47, 95%CI 1.17-5.23, p = 0.02), pro-longed CPB time (OR 2.36, 95%CI 1.05-5.34, p = 0.04), and lower body ischemic time during CPB (OR 2.20, 95%CI 1.05-4.46, p = 0.04) were identified as independent risk factors for AKI. Propensity score-matched anal-ysis showed no significant difference in the risk of AKI following TAR between mild hypothermia or normo-thermia and moderate hypothermia (37.2% vs. 41.9%, p = 0.83). In conclusion, modifiable risk factors for AKI included prolonged CPB time and lower body ischemic time. Temperature management during CPB had no clear effect on outcomes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Glial Cells as Possible Targets of Neuroprotection through Neurotrophic and Antioxidative Molecules in the Central and Enteric Nervous Systems in Parkinson’s Disease 549 556 EN Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/62767 Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. The loss of nigrostriatal dopaminergic neurons produces its characteristic motor symptoms, but PD patients also have non-motor symptoms such as constipation and orthostatic hypotension. The pathological hallmark of PD is the presence of α-synuclein-containing Lewy bodies and neurites in the brain. However, the PD pathology is observed in not only the central nervous system (CNS) but also in parts of the peripheral nervous system such as the enteric nervous system (ENS). Since constipation is a typical prodromal non-motor symptom in PD, often preceding motor symptoms by 10-20 years, it has been hypothesized that PD pathology propagates from the ENS to the CNS via the vagal nerve. Discovery of pharmacological and other methods to halt this progression of neurodegeneration in PD has the potential to improve millions of lives. Astrocytes protect neurons in the CNS by secretion of neurotrophic and antioxidative factors. Similarly, astrocyte-like enteric glial cells (EGCs) are known to secrete neuroprotective factors in the ENS. In this article, we summarize the neuroprotective function of astrocytes and EGCs and discuss therapeutic strategies for the prevention of neurodegeneration in PD targeting neurotrophic and antioxidative molecules in glial cells. No potential conflict of interest relevant to this article was reported.

GID(性同一性障害)学会 Acta Medica Okayama 18835228 12 2019 性的マイノリティ当事者の語りは聴き手の性的マイノリティへの印象や当惑感を改善する 103 110 EN 岡山大学特別支援教育特別専攻科川崎医療福祉大学医療福祉学部 Iori Ohmori Graduate School of Education, Okayama University 本研究の目的は，性的マイノリティ当事者の語りが，聴講者の性的マイノリティへの態度や認識に及ぼす変化を明らかにすることである．当事者が現職の学校教員と校長を対象に50分の講話をし，講演の前後に質問紙調査を行い，印象や当惑感，理解の困難さについて数値化し，変化を調べた．調査内容は，印象の測定にはSD法を使用し，印象の「身近さ」因子に含まれる6項目について7件法で回答を求め，当惑感については8項目，理解困難については2項目の尺度を使用し，6件法で回答を求めた．その結果，参加者は性的マイノリティをより身近に感じるようになり，当惑感や理解困難等の否定的な態度や認識が有意に軽減した． No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1660-4601 18 18 2021 Short or Irregular Sleep Duration in Early Childhood Increases Risk of Injury for Primary School-Age Children: A Nationwide Longitudinal Birth Cohort in Japan 9512 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naomi Matsumoto Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirotsugu Yamamoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences The aim of this study was to investigate the longitudinal relationship between shorter or irregular sleep duration (SD) in early childhood and increased risk of injury at primary school age using data from a nationwide survey in Japan. We categorized SD into seven groups: 6 h, 7 h, 8 h, 9 hrs, 10 or 11 h, >12 h, and irregular, based on questionnaire responses collected at 5.5 years old. The relationship between SD and incidence of injury at 5.5-nine years of age is shown. In addition, we completed a stratified analysis on children with or without problematic behavior at eight years old. We included 32,044 children, of which 6369 were classified as having an injury and 25,675 as not having an injury. Logistic regression model showed that shorter or irregular SD categories were associated with an increased adjusted odds ratio (aOR) for injuries (6 h: aOR 1.40, 95% confidence interval (CI) 1.19-1.66, 7 h: aOR 1.10, 95% CI, 0.98-1.23, 8 h: aOR 1.13, 95% CI, 1.02-1.26, irregular: aOR 1.26, 95% CI 1.10-1.43). The same tendency was observed with shorter or irregular SD in subgroups with or without behavioral problems. Shorter or irregular sleep habits during early childhood are associated with injury during primary school age. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Bendamustine Plus Rituximab as Salvage Treatment for Patients with Relapsed or Refractory Low-grade B-cell Lymphoma and Mantle Cell Lymphoma: A Single-Center Retrospective Study 461 469 EN Hiroyuki Murakami Department of Hematology, National Hospital Organization Okayama Medical Center Takanori Yoshioka Department of Hematology, National Hospital Organization Okayama Medical Center Takashi Moriyama Department of Hematology, National Hospital Organization Okayama Medical Center Tatsunori Ishikawa Department of Hematology, National Hospital Organization Okayama Medical Center Masanori Makita Department of Hematology, National Hospital Organization Okayama Medical Center Kazutaka Sunami Department of Hematology, National Hospital Organization Okayama Medical Center Original Article 10.18926/AMO/62398 Bendamustine plus rituximab (B-R) is an effective therapy for relapsed or refractory (r/r) low-grade B-cell lymphoma (LGBCL) and mantle cell lymphoma (MCL); however, clinical data from Japanese patients treated with B-R therapy are limited. We retrospectively evaluated the efficacy and safety of B-R therapy in 42 patients who received B-R therapy at our hospital for r/r LGBCL and MCL. All patients received intravenous (IV) ritux-imab 375 mg/m2 on day 1 and IV bendamustine 90 mg/m2 on days 2 and 3 every 28 days for up to 6 cycles. The common histologic subtypes were follicular lymphoma (n = 29, 70%), marginal zone lymphoma (n = 6, 14%), and MCL (n = 5, 12%). The overall response rate was 93%, with 62% complete response and complete response unconfirmed. The median progression-free survival (PFS) was 38 months (95% confidence interval [CI], 24.6 to not reached [NR]), and the median overall survival (OS) was 80 months (95% CI, 60.7 to NR). Patients receiving a cumulative dose of bendamustine ≥ 720 mg/m2 showed a significantly longer PFS and OS. Grade 3/4 adverse events (≥ 10%) included neutropenia (55%), lymphopenia (69%), and nausea (24%). B-R therapy was effective and well tolerated, and the cumulative dose of bendamustine was associated with a favorable outcome. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Clinical Course of 60 Cesarean Scar Pregnancies 439 445 EN Takashi Mitsui Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakurako Mishima Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazumasa Tani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jota Maki Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Eto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hayata Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62395 Early diagnosis and therapy are important in a cesarean scar pregnancy (CSP), which can cause uterine rupture with resultant massive bleeding. However, there are some reports of CSPs continued to term. The optimal management of CSPs remains unclear; therefore, we investigated the clinical courses of CSPs diagnosed and treated at perinatal institutions in the Chugoku and Shikoku regions of Japan. We enrolled 60 women diag-nosed with CSP at 21 institutions from January 2006 to December 2015. Of the 60 women diagnosed with CSP, 57 were treated. Pregnancy was terminated in 48 women and continued in 9. Thirteen women underwent transabdominal hysterectomy; they experienced no postoperative complications or allogeneic blood transfu-sion. Nine women received therapies such as dilation and curettage, and 26 received non-surgical therapies such as methotrexate and topical administration of potassium chloride. Among 9 women who chose to con-tinue with their CSP, 7 successfully delivered newborns, 2 had uterine ruptures in the second trimester, and all women required transabdominal hysterectomy. Diagnosis and therapy in the first trimester of pregnancy are important in the management strategy of a CSP. When continuing a CSP, the risk of uterine rupture and trans-abdominal hysterectomy must be considered. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 The Cell Cycle Checkpoint Gene, RAD17 rs1045051, Is Associated with Prostate Cancer Risk 415 421 EN Jingkai Sun Department of Urology, Zhujiang Hospital, Southern Medical University Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Qixu Wang Department of Urology, Zhujiang Hospital, Southern Medical University Akiko Sakai Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ruizhi Xue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chunxiao Liu Department of Urology, Zhujiang Hospital, Southern Medical University Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abai Xu Department of Urology, Zhujiang Hospital, Southern Medical University Peng Huang Department of Urology, Zhujiang Hospital, Southern Medical University Original Article 10.18926/AMO/62379 Human RAD17, as an agonist of checkpoint signaling, plays an essential role in mediating DNA damage. This hospital-based case-control study aimed to explore the association between RAD17 rs1045051, a missense sin-gle nucleotide polymorphism (SNP), and prostate cancer risk. Subjects were 358 prostate cancer patients and 314 cancer-free urology patients undergoing treatment at the Zhujiang Hospital of Southern Medical University in China. RAD17 gene polymorphism rs1045051 was evaluated by the SNaPshot method. Compared with the RAD17 gene polymorphism rs1045051 AA genotype, there was a higher risk of prostate cancer for the CC gen-otype (adjusted odds ratio [AOR] = 1.731, 95% confidence interval [95%CI] = 1.031－2.908, p = 0.038). Compared with the A allele, the C allele was significantly associated with the disease status (AOR = 1.302, 95%CI = 1.037－1.634, p = 0.023). All these findings indicate that in the SNP rs1045051, both the CC genotype and C allele may have a substantial influence on the prostate cancer risk. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Surgical Treatment of Epiretinal Membrane 403 413 EN Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/62378 Epiretinal membrane (ERM) is a common retinal disease characterized by cellular proliferation and metaplasia that lead to the formation of a pathological fibrocellular membrane immediately superjacent to the inner retinal surface. The vast majority of ERMs are considered idiopathic. However, ERM formation can result from various primary intraocular diseases, including retinal breaks and detachment, retinal vascular diseases, and vitreoretinal inflammatory conditions. Although ERMs are generally asymptomatic or cause mild metamorphopsia and/or a modest decrease in visual acuity, some can cause severe macular distortion and macular edema, resulting in significantly impaired function. Surgical removal of ERM is the only treatment, and improvements in vitrectomy systems have enabled less invasive treatment. However, there are currently no standardized criteria for ERM surgery, and the indications for surgery are determined from the patient’s subjective symptoms. Another problem with ERM surgery is that not all patients show satisfactory postoperative recovery of visual function. Thus, further research is needed to determine the criteria for ERM surgery and methods to improve the postoperative prognosis. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0959-8049 153 2021 Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (Telomelysin) with radiotherapy in oesophageal cancer patients unfit for standard treatments 98 108 EN Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Koujima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kuniaki Katsui Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments. Methods: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Results: Of the 13 patients, 7, 3 and 3 patients were treated with 10(10), 10(11) and 10(12) virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8 thorn cells and increased PD-L1 expression. Conclusion: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments. (C) 2021 Elsevier Ltd. All rights reserved. No potential conflict of interest relevant to this article was reported.

e-Century Publishing Corp. Acta Medica Okayama 2156-6976 11 7 2021 Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells 3475 3495 EN Hagar A. Abu Quora Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Maram H. Zahra Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Samah El-Ghlban Division of Biochemistry, Faculty of Science, Menoufia University Neha Nair Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Said M. Afify Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ghmkin Hassan Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hend M. Nawara Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mona Sheta Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sadia Monzur Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Xiaoying Fu Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Amira Osman Department of Histology, Faculty of Medicine, Kafr Elsheikh University Akimasa Seno Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masaharu Seno Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Breast cancer is the first common cause of cancer-related death in women worldwide. Since the malignancy and aggressiveness of breast cancer have been correlated with the presence of breast cancer stem cells, the establishment of a disease model with cancer stem cells is required for the development of a novel therapeutic strategy. Here, we aimed to evaluate the availability of cancer stem cell models developed from mouse induced pluripotent stem cells with the conditioned medium of different subtypes of breast cancer cell lines, the hormonal-responsive T47D cell line and the triple-negative breast cancer BT549 cell line, to generate in vivo tumor models. When transplanted into the mammary fat pads of BALB/c nude mice, these two model cells formed malignant tumors exhibiting pronounced histopathological characteristics similar to breast cancers. Serial transplantation of the primary cultured cells into mammary fat pads evoked the same features of breast cancer, while this result was perturbed following subcutaneous transplantation. The tumors formed in the mammary fat pads exhibited immune reactivities to prolactin receptor, progesterone receptor, green florescent protein, Ki67, CD44, estrogen receptor alpha/beta and cytokeratin 8, while all of the tumors and their derived primary cells exhibited immunoreactivity to estrogen receptor alpha/beta and cytokeratin 8. Cancer stem cells can be developed from pluripotent stem cells via the secretory factors of cancer-derived cells with the capacity to inherit tissue specificity. However, cancer stem cells should be plastic enough to be affected by the microenvironment of specific tissues. In summary, we successfully established a breast cancer tumor model using mouse induced pluripotent stem cells developed from normal fibroblasts without genetic manipulation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1615-5289 22 1 2021 Effective highlighting modes of graphical user interfaces in visual information search 111 119 EN Toshihisa Doi Okayama University This study discusses the preferred highlighting mode for graphical user interface (GUI) design. The study investigated the effects of different highlighting modes on the search time and accuracy of the element on the screen. The experimental factors were the type of highlighting (color, bold, or color and bold), the target highlighting (highlighted or not highlighted), and the number of elements on GUI (few or many). The participants had to search for a predetermined target on the screen. The evaluation measures were the reaction time and percentage correctly identified. The statistical analysis result shows that bold highlighting had the shortest search time, and color highlighting had the worst accuracy. Under the conditions of this experiment, bold highlighting should contribute to the design of the screen for an easier search of information in terms of both search speed and accuracy. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2198-7793 7 1 2021 Gastroenteropancreatic neuroendocrine tumor of the accessory papilla of the duodenum: a case report 156 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroki Sato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences BackgroundContrary to the increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), GEP-NETs of the accessory papilla of the duodenum are extremely rare. Furthermore, there have been no recommendations regarding the treatment strategy for GEP-NETs of the accessory papilla of the duodenum. We present a case of GEP-NET of the accessory papilla of the duodenum successfully treated with robotic pancreatoduodenectomy.Case presentationA case of a 70-year-old complaining of no symptoms was diagnosed with GEP-NET of the accessory papilla of the duodenum. A 8-mm tumor was located at the submucosal layer with a biopsy demonstrating a neuroendocrine tumor grade 1. The patient underwent robotic pancreatoduodenectomy as curative resection for the tumor. The total operative time was 406 min with an estimated blood loss of 150 mL. The histological examination revealed a well-differentiated neuroendocrine tumor with low Ki-67 index (<1%). In the posterior areas of the pancreas, the lymph node metastases were detected. The patient was followed up for 6 months with no recurrence postoperatively.ConclusionsConsidering the potential risks of the lymph node metastases, the standard treatment strategy for GEP-NETs of the accessory papilla of the duodenum should be radical resection with pancreatoduodenectomy. Minimally invasive approach can be the alternative to the conventional open surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Relationships among Bone Metabolic Markers, Body Fat Composition and Carotid Intima–Media Thickness in Premenopausal Obese Women 373 379 EN Guzin F. Yaylali Department of Endocrinology and Metabolism, Pamukkale University Ozen Dedeoglu Department ofInternal Medicine, Pamukkale University Senay Topsakal Department of Endocrinology and Metabolism, Pamukkale University Duygu Herek Department of Radiology, Pamukkale University Hande Senol Department of Biostatistics, Pamukkale University Original Article 10.18926/AMO/62233 Osteocalcin (OC) is inversely related to body fat distribution and fasting glucose levels. We sought to observe the effect of OC on fat distribution and subclinical atherosclerosis as measured by carotid intima-media thickness (CIMT) in premenopausal obese women. In this prospective observational study, totally, 73 premenopausal obese women (aged 17-55 years) and 53 healthy women (aged 20-50 years) with normal weight were included as controls. Anthropometric measurements, total fat and fat ratio, insulin, fasting blood glucose, and OC levels were estimated. Ultrasonography was used to assess fat distribution, and fat thickness was measured in 4 regions. Subcutaneous fat (SCF), visceral fat (VF), and preperitoneal fat (PPF) thicknesses were considerably higher in obese subjects (p<0.01) than healthy controls, while OC levels were significantly lower. No correlation was observed between OC levels and SCF, VF, or PPF. In a multiple regression analysis, OC was significantly positively associated with SCF (p=0.04, Beta=0.284). No associations were observed between OC levels and VF, PPF, or CIMT. A significant association was observed between parathyroid hormone (PTH) and VF (p=0.021, Beta=0.284), and vitamin D levels were inversely associated with VF (p=0.002, r=－0.366). OC levels were lower in premenopausal obese women than normal-weight healthy controls, but OC exhibited no correlation with VF or PPF, and only a weak positive association with SCF. Additionally, VF was positively correlated with PTH and inversely correlated with vitamin D. These results suggest that OC may be an early indicator of lipid accumulation in te subcutaneous area and development of atherosclerosis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Role of the Transcription Factor BTB and CNC Homology 1 in a Rat Model of Acute Liver Injury Induced by Experimental Endotoxemia 363 372 EN Nohito Tanioka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emiko Omori Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Takahashi Faculty of Health and Welfare Science, Okayama Prefectural University Masakazu Yamaoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62232 Hepatic oxidative stress plays an important role in the pathogenesis of several acute liver diseases, and free heme is thought to contribute to endotoxemia-induced acute liver injury. The heme oxygenase 1 (HO-1) gene is upregulated and the δ-aminolevulinate synthase (ALAS1) gene is downregulated in the rat liver following lipopolysaccharide (LPS) treatment. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that normally represses HO-1 expression. In this study, we evaluated the changes in HO-1, ALAS1, and Bach1 expression and nuclear Bach1 expression in rat livers following intravenous LPS administration (10 mg/kg body weight). LPS significantly upregulated HO-1 mRNA and downregulated ALAS1 mRNA in the rat livers, suggesting that hepatic free heme concentrations are increased after LPS treatment. Bach1 mRNA was strongly induced after LPS injection. In contrast, nuclear Bach1 was significantly but transiently decreased after LPS treatment. Rats were also administered hemin (50 mg/kg body weight) intravenously to elevate heme concentrations, which decreased nuclear Bach1 levels. Our results suggest that elevated hepatic free heme may be associated with a decline of nuclear Bach1, and induction of Bach1 mRNA may compensate for the decreased nuclear Bach1 after LPS treatment in the rat liver. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Texture Indices of 18F-FDG PET/CT for Differentiating Squamous Cell Carcinoma and Non-Hodgkin’s Lymphoma of the Oropharynx 351 356 EN Katsuya Mitamura Department of Radiology, Faculty of Medicine, Kagawa University Takashi Norikane Department of Radiology, Faculty of Medicine, Kagawa University Yuka Yamamoto Department of Radiology, Faculty of Medicine, Kagawa University Ayumi Ihara-Nishishita Department of Radiology, Faculty of Medicine, Kagawa University Takuya Kobata Department of Radiology, Faculty of Medicine, Kagawa University Kengo Fujimoto Department of Radiology, Faculty of Medicine, Kagawa University Yasukage Takami Department of Radiology, Faculty of Medicine, Kagawa University Nobuyuki Kudomi Department of Medical Physics, Faculty of Medicine, Kagawa University Hiroshi Hoshikawa Department of Otolaryngology, Faculty of Medicine, Kagawa University Yoshihiro Nishiyama Department of Radiology, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/62230 We assessed the role of 18F-FDG PET/CT texture indices for the differentiation of squamous cell carcinoma (SCC) and non-Hodgkin’s lymphoma (NHL) in the oropharynx. 18F-FDG PET/CT data for 27 patients with SCC and 25 patients with NHL in the oropharynx were investigated. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and six texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis [LGZE], and high graylevel zone emphasis [HGZE]) were derived from PET images. PET/CT parameters of the SCC patients were compared with those of the NHL patients. The diagnostic accuracy of the indices for differentiating SCC from NHL was calculated by a receiver operating characteristic curve analysis. 18F-FDG uptake in the oropharynx was observed in all of the patients. The SUVmax, MTV, and TLG did not differ significantly between the SCC and NHL groups, but two of the six texture indices (LGZE [p=0.004] and HGZE [p=0.03]) showed significant differences between the groups. LGZE was the best discriminative index for the differentiation of SCC and NHL (55.6% sensitivity, 88.0% specificity). The LGZE and HGZE texture indices derived from 18F-FDG PET/CT images may be useful in differentiating SCC and NHL in the oropharynx. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Gender Expression among Transgender Women in Japan: Support Is Needed to Improve Social Passing as a Woman 323 334 EN Michiyo Furutani Graduate School of Health Sciences, Okayama University Zhou Yu Graduate School of Health Sciences, Okayama University Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/62227 Gender expression is important for transgender women to improve their social passing as women. Herein, a questionnaire about the status of gender expression and support needs was distributed to 54 transgender women aged 17-71 in Japan. Most of the respondents noted that they had found it relatively difficult to handle physical changes and weight gain due to hormone treatment. They also found it difficult to enact and sustain practices such as a feminine use of voice and to use women-only services, whereas practicing and continuing with routine skin and hair care and feminine mannerisms were relatively easy for them. In the questionnaire regarding the support for gender transitioning, many items showed only a small percentage of the transgender women had received the support that they were looking for, and most of their needs for support were not addressed. Some of the factors that increased the respondents’ needs and achievement of gender expression as women included estrogen treatment, sex reassignment surgery, and living as a woman; these aspects met their support needs as well. Gender support professionals need to coordinate and collaborate with specialists in areas such as nutritional guidance and voice training to enable transgender women to improve the extent to which they can socially ‘pass’ as women. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Validity and Reliability of the Japanese Version of the 12-item Self-administered World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in Patients with Schizophrenia 315 322 EN Riho Wada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoki Nakaya Department of Health Sciences, Saitama Prefectural University Maiko Fujimori Division of Health Care Research, Behavioral Sciences and Survivorship Research Group, National Cancer Center Ryuhei So Okayama Psychiatric Medical Center Masafumi Kodama Okayama Psychiatric Medical Center Yuji Higuchi Care of Your Mind, Taiyo Hills Hospital Kyoko Kakeda Department of Neuropsychiatry, Kochi Medical School, Kochi University Yosuke Uchitomi Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center Hospital Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masatoshi Inagaki Department of Psychiatry, Faculty of Medicine, Shimane University Original Article 10.18926/AMO/62226 It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach’s alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=－0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1743-9191 89 2021 Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study 105946 EN Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Okayama University Hospital Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Watanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Kuwada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Tsumura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University School of Medicine Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Pharmacologic prophylaxis such as enoxaparin for venous thromboembolism (VTE) is rarely used in Japan, even following abdominal cancer surgery, for which it is recommended in relevant guidelines (at least 7 days of use) along with mechanical prophylaxis with intermittent pneumatic compression. Reasons for enoxaparin’s unpopularity include concerns over postoperative bleeding and its inconvenience in clinical practice. Here, we conducted a prospective clinical study of short-term (3 days) use of enoxaparin, which is considered to minimally impact postoperative management without increasing bleeding risk. Methods: Gastric cancer patients who underwent gastrectomy received enoxaparin for 3 days from postoperative day (POD) 1 to 4. The primary endpoint was the incidence of deep vein thrombosis (DVT), which was examined primarily via Doppler ultrasonography of the lower limbs between POD 8 and 14. The planned sample size was 70, which was calculated based on an estimated incidence rate of 9% and an upper limit of incidence rate of 20%, with alpha of 0.05 and beta of 0.2. Results: A total of 70 gastric cancer patients were enrolled, and ultimately, 68 patients received the protocol intervention and DVT evaluation. Sixty-seven patients completed 6 enoxaparin injections, but 1 patient did not complete the course due to abdominal bleeding after initiation. The incidence of DVT was 4.4% (3/68), and the 95% upper confidence interval was 12.2%, lower than the 20% threshold we set as the upper limit of DVT incidence. DVT was detected only in the peripheral veins of the lower extremities in all 3 affected patients. The incidence of bleeding-related complications, which were not severe, was 1.5% (1/68). Conclusions: Short-term (3 days) use of enoxaparin was shown to be effective and safe for VTE prophylaxis, comparable to regular use (at least 7 days), in postoperative management of gastric cancer surgery. No potential conflict of interest relevant to this article was reported.

Dove Medical Press Ltd. Acta Medica Okayama 1178-2013 16 2021 Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment 2775 2787 EN Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chaoming Li Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naijin Xu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ruizhi Xue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abai Xu Department of Urology, Zhujiang Hospital, Southern Medical University Motoo Araki Okayama University Hospital Ruifen Sun Center for Scientific Research, Yunnan University of Chinese Traditional Medicine Chunxiao Liu Department of Urology, Zhujiang Hospital, Southern Medical University Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peng Huang Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9 +/- 1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96 +/- 1.88)% compared with (0.99 +/- 0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy. No potential conflict of interest relevant to this article was reported.

Wolters Kluwer Medknow Publications Acta Medica Okayama 2394-8108 7 1 2021 An Examination of mobile spinal cord stimulators on treating Parkinson disease 8 12 EN Zhen-Jie Wang Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida Takao Yasuhara Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University In animal models of Parkinson disease (PD), spinal cord stimulation (SCS) exhibits neuroprotective effects. Recent advancements in SCS technology, most importantly mobile stimulators, allow for the conventional limitations of SCS such as limited stimulation time and restricted animal movements to be bypassed, offering potential avenues for improved clinical translation to PD patients. Small devices that could deliver continuous SCS to freely moving parkinsonian rats were shown to significantly improve behavior, preserve neurons and fibers in the substantia Nigra/striatum, reduce microglia infiltration, and increase laminin-positive area of the cerebral cortex. Through possible anti-inflammatory and angiogenic mechanisms, it has been demonstrated that there are behavioral and histological benefits to continuous SCS in a time-dependent manner. This review will discuss the benefits of this technology as well as focus on the limitations of current animal models. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 61 1 2021 Follow-up with serum IgG4-monitoring in 8 patients with IgG4-related disease diagnosed by a lacrimal gland mass 10 20 EN Toshihiko Matsuo Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitomi Kataoka Department of General Medicine, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Hospital Daisuke Ennishi Department of Hematology/Oncology, Okayama University Hospital Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 2056-5968 7 1 2021 Antenna arrangement and energy-transfer pathways of PSI-LHCI from the moss Physcomitrella patens 10 EN Qiujing Yan Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Liang Zhao State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University Wenda Wang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Xiong Pi State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University Guangye Han Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Jie Wang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Lingpeng Cheng State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University Yi-Kun He College of Life Sciences, Department of Chemistry, Capital Normal University, Tingyun Kuang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Xiaochun Qin School of Biological Science and Technology, University of Jinan Sen-Fang Sui State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University Jian-Ren Shen Research Institute for Interdisciplinary Science, and Graduate School of Natural Science and Technology, Okayama University, Plants harvest light energy utilized for photosynthesis by light-harvesting complex I and II (LHCI and LHCII) surrounding photosystem I and II (PSI and PSII), respectively. During the evolution of green plants, moss is at an evolutionarily intermediate position from aquatic photosynthetic organisms to land plants, being the first photosynthetic organisms that landed. Here, we report the structure of the PSI-LHCI supercomplex from the moss Physcomitrella patens (Pp) at 3.23 angstrom resolution solved by cryo-electron microscopy. Our structure revealed that four Lhca subunits are associated with the PSI core in an order of Lhca1-Lhca5-Lhca2-Lhca3. This number is much decreased from 8 to 10, the number of subunits in most green algal PSI-LHCI, but the same as those of land plants. Although Pp PSI-LHCI has a similar structure as PSI-LHCI of land plants, it has Lhca5, instead of Lhca4, in the second position of Lhca, and several differences were found in the arrangement of chlorophylls among green algal, moss, and land plant PSI-LHCI. One chlorophyll, PsaF-Chl 305, which is found in the moss PSI-LHCI, is located at the gap region between the two middle Lhca subunits and the PSI core, and therefore may make the excitation energy transfer from LHCI to the core more efficient than that of land plants. On the other hand, energy-transfer paths at the two side Lhca subunits are relatively conserved. These results provide a structural basis for unravelling the mechanisms of light-energy harvesting and transfer in the moss PSI-LHCI, as well as important clues on the changes of PSI-LHCI after landing. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-462X 11 2021 Cytosolic Free N-Glycans Are Retro-Transported Into the Endoplasmic Reticulum in Plant Cells 610124 EN Makoto Katsube Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University Natsuki Ebara Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University Megumi Maeda Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University Yoshinobu Kimura Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University During endoplasmic reticulum (ER)-associated degradation, free N-glycans (FNGs) are produced from misfolded nascent glycoproteins via the combination of the cytosolic peptide N-glycanase (cPNGase) and endo-beta-N-acetylglucosaminidase (ENGase) in the plant cytosol. The resulting high-mannose type (HMT)-FNGs, which carry one GlcNAc residue at the reducing end (GN1-FNGs), are ubiquitously found in developing plant cells. In a previous study, we found that HMT-FNGs assisted in protein folding and inhibited beta-amyloid fibril formation, suggesting a possible biofunction of FNGs involved in the protein folding system. However, whether these HMT-FNGs occur in the ER, an organelle involved in protein folding, remained unclear. On the contrary, we also reported the presence of plant complex type (PCT)-GN1-FNGs, which carry the Lewis(a) epitope at the non-reducing end, indicating that these FNGs had been fully processed in the Golgi apparatus. Since plant ENGase was active toward HMT-N-glycans but not PCT-N-glycans that carry beta 1-2xylosyl and/or alpha 1-3 fucosyl residue(s), these PCT-GN1-FNGs did not appear to be produced from fully processed glycoproteins that harbored PCT-N-glycans via ENGase activity. Interestingly, PCT-GN1-FNGs were found in the extracellular space, suggesting that HMT-GN1-FNGs formed in the cytosol might be transported back to the ER and processed in the Golgi apparatus through the protein secretion pathway. As the first step in elucidating the production mechanism of PCT-GN1-FNGs, we analyzed the structures of free oligosaccharides in plant microsomes and proved that HMT-FNGs (Man(9-7)GlcNAc(1) and Man(9-8)GlcNAc(2)) could be found in microsomes, which almost consist of the ER compartments. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Successful Bronchoscopic Treatment for Postoperative Bronchopleural Fistula Using N-butyl-2-cyanoacrylate (NBCA): Report of a Post-completion Pneumonectomy Case with a History of Induction Chemoradiotherapy Followed by Bilobectomy for Advanced Lung Cancer 91 94 EN Toshio Shiotania Department of Organ Transplantation Center, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Riko Katsube Department of Thoracic Surgery, Okayama University Hospital Yasuaki Tomioka Department of Organ Transplantation Center, Okayama University Hospital Ken Suzawa Department of Thoracic Surgery, Okayama University Hospital Kentaroh Miyoshi Department of Thoracic Surgery, Okayama University Hospital Shinji Otani Department of Thoracic Surgery, Okayama University Hospital Mikio Okazaki Department of Thoracic Surgery, Okayama University Hospital Seiichiro Sugimoto Department of Organ Transplantation Center, Okayama University Hospital Junichi Sohb Department of Thoracic Surgery, Okayama University Hospital Masaomi Yamane Department of Thoracic Surgery, Okayama University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Case Report 10.18926/AMO/61440 Bronchopleural fistula (BPF) is a severe complication following lung resection. We present the case of a patient with a history of advanced lung cancer, who had undergone induction chemoradiotherapy followed by right middle and lower lobectomy, and who developed BPF after completion right pneumonectomy. Although we had covered the bronchial stump with an omental pedicled flap, BPF was found on postoperative day 19. We covered the fistula with n-butyl-2-cyanoacrylate (NBCA) using bronchoscopy. Although we had to repeat the NBCA treatment, we ultimately cured the patient’s BPF and no recurrence was observed up to 15.2 months after surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 The Optimal Prepregnancy Body Mass Index for Lactation in Japanese Women with Neonatal Separation as Analyzed by a Differential Equation 63 69 EN Katsuhiko Tada Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Yasunari Miyagi Miyake Ofuku Clinic Kazue Nakamura Department of Neonatology, National Hospital Organization, Okayama Medical Center Moe Yorozu Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Emi Fukushima Department of Nursing, National Hospital Organization, Okayama Medical Center Kazumasa Kumazawa Department of Obstetrics and Gynecology, National Hospital Organization, Okayama Medical Center Makoto Nakamura Department of Neonatology, National Hospital Organization, Okayama Medical Center Misao Kageyama Department of Neonatology, National Hospital Organization, Okayama Medical Center Original Article 10.18926/ATM/61436 We used a differential equation to identify the biological relationship between the maternal prepregnancy body mass index (BMI) and lactation on postpartum day 4 in Japanese women with neonatal separation. This retro-spective observational study included 252 mothers (135 primiparas, 117 multiparas) whose singleton neonates were admitted to a neonatal ICU. We formulated hypotheses based on breast anatomy to analyze the relation-ship between the expressed milk obtained on postpartum day 4 and the maternal prepregnancy BMI with the following differential equation: y’(x) = k y(x)/x, where k is the constant, x is the prepregnancy BMI, and y is the expressed milk volume. The formula was then obtained as y(x) = axk, where a is the constant. The Akaike information criterion (AIC) was used to estimate the regression equation with the maximum likelihood for primiparas and multiparas. The best criteria for BMI determined by the AIC were 20.89 kg/m2 in primiparas and 20.19 kg/m2 in multiparas. These were the optimal BMI values for lactation, coinciding with the median prepregnancy BMI in the study population (20.78 kg/m2 in primiparas and 20.06 kg/m2 in multiparas). The formula based on biomathematics might help establish the biological relationship between prepregnancy BMI and breastmilk volume. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Thoracoscopic Localization of Small Peripheral Pulmonary Lesions Using Percutaneous Computed Tomography-guided Pleural Dye Marking: A Retrospective Analysis 55 61 EN Yujiro Kubo Department of Thoracic Surgery, Iwakuni Clinical Center Mototsugu Watanabe Department of Thoracic Surgery, Iwakuni Clinical Center Haruki Choshi Department of Thoracic Surgery, Iwakuni Clinical Center Kei Matsubara Department of Thoracic Surgery, Iwakuni Clinical Center Toshio Shiotani Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Kataoka Department of Thoracic Surgery, Iwakuni Clinical Center Original Article 10.18926/AMO/61435 Small pulmonary lesions are often difficult to localize during thoracoscopic surgery. We describe a new com-puted tomography (CT)-guided pleural dye-marking method for small peripheral pulmonary lesions that does not involve a visceral pleural puncture. We used this technique for 23 lesions (22 patients) who underwent tho-racoscopic partial lung resection (Nov. 2016-Jan. 2018). With the patient in the lateral decubitus position, pre-operative CT-guided marking on the skin over the lesion was performed. During the surgery, we marked the visceral pleura with a skin marker directly or with an infant-size nutrition catheter with crystal violet at the tip through a venous indwelling needle inserted perpendicular to the skin marking. We localized and resected the lesions in all cases, without complications. The median nodule size measured histopathologically was 8 (4-20) mm overall, and 7 (0-20) mm of the solid part; the median distance from the visceral pleura to the nodule was 9 (1-33) mm. The median operation time was 67 (37-180) min. The median postoperative hospital stay was 3 (3-11) days. Our CT-guided pleural dye-marking method is useful and safe for the localization of small periph-eral pulmonary lesions in thoracoscopic partial lung resections. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Clinical Characteristics of Low Androgen Status in Males with Type 2 Diabetes Mellitus 1 8 EN Jun Hamahara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Hanayama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayuki Kishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/61424 To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 ± 1.5 years old), decreases in serum FT levels to < 8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The per-centages of patients with low FT levels were high in the ≥ 50 years age group (83%), the HbA1c < 7% group (67%), and the 25 ≤ BMI < 30 kg/m2 group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R = 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = －0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R = 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males. No potential conflict of interest relevant to this article was reported.

Nature Acta Medica Okayama 2373-8065 7 2021 Gravity sensing in plant and animal cells 2 EN Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideyuki Takahashi Graduate School of Life Sciences, Tohoku University Takuya Furuichi Faculty of Human Life Sciences, Hagoromo University of International Studies Masatsugu Toyota Department of Biochemistry and Molecular Biology, Saitama University Makoto Furutani-Seiki Department of Systems Biochemistry in Regeneration and Pathology, Graduate School of Medicine, Yamaguchi University Takeshi Kobayashi Department of Integrative Physiology, Graduate School of Medicine, Nagoya University Haruko Watanabe-Takano Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute Masahiro Shinohara Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities Takuro Numaga-Tomita Department of Molecular Pharmacology, Shinshu University School of Medicine Asako Sakaue-Sawano Lab for Cell Function and Dynamics, CBS, RIKEN Atsushi Miyawaki Lab for Cell Function and Dynamics, CBS, RIKEN Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-230X 21 1 2021 Utility of a 21-gauge Menghini-type biopsy needle with the rolling method for an endoscopic ultrasound-guided histological diagnosis of autoimmune pancreatitis: a retrospective study 21 EN Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Toru Ueki Departments of Internal Medicine, Fukuyama City Hospital Yasuhiro Noma Department of Internal Medicine, National Hospital Organization Fukuyama Medical Center Kunihiro Omonishi Departments of Internal Medicine and Pathology, Fukuyama City Hospital Kyotaro Ohno Departments of Internal Medicine and Pathology, Fukuyama City Hospital Soichiro Kawahara Departments of Internal Medicine, Fukuyama City Hospital Takashi Oda Departments of Internal Medicine, Fukuyama City Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital Background The histological diagnosis of autoimmune pancreatitis (AIP) by an endoscopic ultrasound (EUS)-guided approach is still challenging. Methods We investigated the utility of the 21-gauge Menghini-type biopsy needle with the rolling method for the histological diagnosis of AIP, in comparison with conventional 22-gauge needles. Among total 28 patients, rate of definitive histological diagnosis, acquired sample area of tissue, rate of histopathological diagnosis of AIP, and adverse events were retrospectively analyzed. Results Definitive histological diagnoses were successfully accomplished in all 14 patients (100%) treated with a Menghini-type needle, and in 57% of cases (8/14) treated with conventional 22-gauge needles (P < 0.001). The median sample area of the tissue, except for blood contamination, was remarkably larger by the Menghini-type needle than by conventional-type needles (6.2 [IQR, 4.5–8.8] versus 0.7 [IQR, 0.2–2.0] mm2, P < 0.001), and the area per punctures was approximately 4 times larger (1.4 [IQR: 0.9–2.9] versus 0.3 [IQR: 0.1–0.6] mm2/puncture, P < 0.001). Based on the International Consensus Diagnostic Criteria, lymphoplasmacytic infiltration, abundant IgG4-postive cells, storiform fibrosis, and obliterative phlebitis were found in 86%/29%, 64%/0%, 36%/0%, and 7%/0% patients who were treated with the Menghini-type needle and conventional-type needles, respectively. Consequently, histopathological diagnosis with type 1 AIP (lever 1 or 2) was achieved in 9 patients (64%) treated with the Menghini-type needle and in no patient treated with conventional-type needles (P < 0.001). Two patients who had mild post-procedural pancreatitis improved with conservative treatment, and no bleeding occurred in patients treated with the Menghini-type needle. Conclusion EUS-guided rolling method with the 21-gauge Menghini-type biopsy needle is useful for the histopathological diagnosis of AIP, due to its abundant acquisition of good-quality tissue from the pancreas. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 1349-7235 59 11 2020 Clinical Characteristics and Risk Factors for Rebleeding in Patients with Obscure Gastrointestinal Bleeding 1345 1350 EN Yuki Baba Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Harada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective With the advent of capsule endoscopy (CE) and double-balloon endoscopy (DBE), the diagnosis and treatment of obscure gastrointestinal bleeding (OGIB) have markedly progressed. However, rebleeding sometimes occurs and is difficult to diagnose and treat. The aim of the present study was to investigate the clinical features of OGIB and risk factors for rebleeding in our hospital. Methods A total of 195 patients who underwent CE and/or DBE for OGIB in our hospital from January 2009 to July 2016 were included in the present study. We analyzed 168 cases of small intestinal OGIB, after excluding 27 cases of extra small intestinal bleeding. The clinical characteristics and risk factors related to rebleeding were retrospectively studied. Results Among the 168 patients who were included in the analysis, 95 patients (56.5%) were male. The mean age was 64.5 years (range, 8 to 87 years). Hypertension (31.0%) was the most frequent comorbidity, followed by chronic kidney disease (19.0%). The final diagnoses were ulcerative lesions (n=50, 29.8%), vascular lesions (n=30, 17.9%), tumors (n=7, 4.2%), and diverticula (n=2, 1.2%). The bleeding source was undetermined in the remaining 79 cases (47.0%). Rebleeding was confirmed in 29 cases (17.3%). In a univariate analysis, chronic kidney disease, vascular lesions, and overt previous bleeding were significantly associated with the risk of rebleeding. A multivariate analysis showed that chronic kidney disease, vascular lesion, and overt previous bleeding were significantly associated with the risk of rebleeding. Conclusion Patients with OGIB with overt previous bleeding, vascular lesions, and/or chronic kidney disease had a higher risk of rebleeding. No potential conflict of interest relevant to this article was reported.

Department of Mathematics, Faculty of Science, Okayama University Acta Medica Okayama 0030-1566 8 2 1958 Galois theory of simple rings IV 189 194 EN Takasi Nagahara Nobuo Nobusawa Hisao Tominaga No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants 557 562 EN Mikako Ishiguro Department of Internal Medicine, Tsuyama Chuo Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Kenichiro Ogura Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Akira Hiratsuka Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences Hiromasa Takeda Department of Internal Medicine, Tsuyama Chuo Hospital Daisuke Kawai Department of Internal Medicine, Tsuyama Chuo Hospital Hirofumi Tsugeno Department of Internal Medicine, Tsuyama Chuo Hospital Shigeatsu Fujiki Department of Internal Medicine, Tsuyama Chuo Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61217 A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Antenatal Care Visits and Adverse Pregnancy Outcomes at a Hospital in Rural Western Province, Rwanda 495 503 EN Simba Akintije Calliope Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University Takashi Yorifuji Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Wada Graduate School of Human Life Science, Osaka City University Marie Goret Mukakarake Mibilizi District Hospital Leon Mutesa Center for Human Genetics, College of Medicine and Health Sciences, University of Rwanda Taro Yamamoto Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University Original Article 10.18926/AMO/61209 In many economically developing countries, and especially in the rural regions of sub-Saharan African coun-tries, there have been only limited investigations into the association between antenatal care (ANC) and adverse pregnancy outcomes. We obtained information on ANC and pregnancy outcomes between 2011 and 2016 from hospital files of pregnant women (n = 4,960) served at a rural hospital in Rwanda, and we examined the associa-tions between their ANC visits and the adverse pregnancy and neonatal outcomes by using univariate and mul-tivariate logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Most of the pregnant women had ≥ 4 ANC visits, but 39% (n = 1,911) did not have ≥ 3 visits before delivery. The prev-alence of low birth weight (LBW) and that of preterm birth (PTB) were 12% and 9.9%, respectively. Compared to the women who attended only one ANC visit, those who attended ≥ 4 ANC visits had lower risks of LBW (OR 0.20; 95%CI: 0.11-0.36) and PTB (OR 0.28; 95%CI: 0.11-0.76). Frequent ANC visits were also associ-ated with better postnatal outcomes of the newborns. Encouraging women to attend ANC visits before delivery can markedly reduce PTB-related and LBW-related complications, especially in resource-limited settings. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Reality of Gastric Cancer in Young Patients: The Importance and Difficulty of the Early Diagnosis, Prevention and Treatment 461 466 EN Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/61204 Gastric cancer usually arises in middle-aged to older patients, and is rarely found in younger patients. The clin-ical characteristics, etiology, prognosis, preventive methods and treatment of gastric cancer in young patients have not been fully investigated because of its low prevalence. In this review, we discuss the current under-standing and clinical problems associated with gastric cancer in young patients. Helicobacter pylori (H. pylori), which is a major cause of gastric cancer, especially in older populations, is closely associated with gastric cancer in young patients as well as in older patients. Gastric cancer in young patients tends to be diagnosed at an advanced stage with alarm symptoms. However, young patients with advanced gastric cancer tend to have a favorable general condition and organ function, so they can tolerate intensive systematic chemotherapy. Unfortunately, the prognosis of gastric cancer in young patients with an advanced stage is not favorable. We should not take this rare disease lightly, given its poor prognosis if patients are diagnosed at an unresectable stage. The evaluation of the H. pylori infection status and performance of H. pylori eradication therapy to prevent gastric cancer in young patients as well as the development of more intensive chemotherapy regimens for unre-sectable gastric cancer in young patients are warranted. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 175 2020 性別役割意識と実態― 韓国昌原市における未就学児の親調査にもとづいて ― 57 68 EN 10.18926/bgeou/61002 　本研究の目的は，韓国の昌原市に居住する子育て期の父親と母親の役割意識と実態を把握，分析することである。2016年９月から10月に幼稚園，保育所等の協力を得て質問紙による調査を実施した。質問紙は，父親，母親，祖父母用をセットにした500部を配布，父親217部，母親257部，祖父母54部を回収し，本稿では父親と母親票を分析した。平均年齢は父親が39.4歳，母親が37.6歳，子どもは２人が最も多い。家事・育児は，概ね母親が行っており，父親の３割強，母親の４割強は，家事・育児遂行の現状を不公平と感じ，父親の２割，母親の５割は，父親の育児担当を増やしたいと希望していた。父親の６割，母親の４割強は，「夫は生活費，妻は家事・育児」という役割分業を支持する一方で，６割前後の父親と母親は，「夫は家事・育児，妻は生活費」という逆の形も支持していた。父親と母親の８割以上が家事・育児を平等に分担すべきと考え，父親の５割，母親の６割が生活費を平等に分担すべきと考えていた。本調査の結果，多くの父親と母親は，夫婦における役割遂行について柔軟に考えようとしており，変化がみられていることを確認することができた。 No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2020 Annexin A2–STAT3–Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma EN Yuji Matsumoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 読み書き能力の発達― 就学前から小学2 年生までの追跡研究― 74 82 EN Kaoru Hanafusa Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 　To elucidate the development of reading and writing abilities among Japanese children, we investigated the scores on 13 reading/writing tasks over a 3-year period among children from preschool age (5 to 6 years old) to the second grade of elementary school (7 to 8 years old). Most of 92 subjects (42 girl, 50 boys) completed all 13 tasks. Preschool-age children were given a hiragana naming task (HNT). The five tasks in the first grade were related to reading and writing hiragana, and the seven tasks in the second grade were related to reading and writing both hiragana and kanji. The preschoolers’ median score on the HNT was 38.0 points (max 40.0), and six children had extremely low scores (5-14 points). Twenty-three children (9 girls, 14 boys) had HNT scores below 32.0 points, and these children also tended to have poor scores on the reading/writing tasks in the first and second grade. The children’s HNT scores showed significantly positive correlations with their scores on the hiragana writing task and the kanji reading/writing tasks. The HNT scores also showed significantly negative correlations with the duration of reading in four reading tasks. These results suggest that evaluations of the HNT score in preschool-age children may be useful to predict the reading/writing abilities of school-age children. No potential conflict of interest relevant to this article was reported.

British Editorial Society of Bone and Joint Surgery Acta Medica Okayama 2049-4394 102-B 8 2020 The role of radiotherapy in the treatment of superficial soft-tissue sarcomas 1088 1094 EN Tomohiro Fujiwara Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Tsuda The Royal Orthopaedic Hospital NHS Foundation Trust Louis-Romée Le Nail The Royal Orthopaedic Hospital NHS Foundation Trust Scott Evans The Royal Orthopaedic Hospital NHS Foundation Trust Jonathan Gregory The Royal Orthopaedic Hospital NHS Foundation Trust Roger Tillman The Royal Orthopaedic Hospital NHS Foundation Trust Adesegun Abudu The Royal Orthopaedic Hospital NHS Foundation Trust Aims The existing clinical guidelines do not describe a clear indication for adjuvant radiotherapy (RT) in the treatment of superficial soft tissue sarcomas (STSs). We aimed to determine the efficacy of adjuvant RT for superficial STSs. Methods We retrospectively studied 304 patients with superficial STS of the limbs and trunk who underwent surgical resection at a tertiary sarcoma centre. The efficacy of RT was investigated according to the tumour size and grade: group 1, ≤ 5 cm, low grade; group 2, ≤ 5cm, high grade; group 3, > 5 cm, low grade; group 4, > 5 cm, high grade. Results The five- and ten-year local recurrence-free survival (LRFS) for all patients was 88% and 81%, respectively. While the efficacy of adjuvant RT was not proven in local control of all patients (five-year LRFS; RT+, 90% versus RT-, 83%; p = 0.074), the LRFS was significantly improved by adjuvant RT in group 2 (five-year LRFS; RT+, 96% versus RT-, 82%; p = 0.019), and group 4 (five-year LRFS; RT+, 87% versus RT-, 73%; p = 0.027). In groups 2 and 4, adjuvant RT significantly reduced the LR risk if the resection margin was clear but less than 5 mm; the LR rate was 7% with adjuvant RT compared with 26% with surgery alone (p = 0.003). There was no statistical relationship with the use of adjuvant RT and survival in every group. Conclusion Adjuvant RT reduces the risk of local recurrence in patients with superficial high-grade STS regardless of tumour size, especially when resection margin is less than 5 mm. No potential conflict of interest relevant to this article was reported.

British Editorial Society of Bone and Joint Surgery Acta Medica Okayama 2049-4394 101-B 8 2019 Preoperative surgical risk stratification in osteosarcoma based on the proximity to the major vessels 1024 1031 EN T. Fujiwara Department of Orthopaedic Surgery, Okayama University Hospital M. R. Medellin Department of Orthopaedic Oncology, The Royal Orthopaedic Hospital A. Sambri Department of Orthopaedic Oncology, The Royal Orthopaedic Hospital Y. Tsuda Department of Orthopaedic Oncology, The Royal Orthopaedic Hospital J. Balko Department of Musculoskeletal Pathology, The Royal Orthopaedic Hospital V. Sumathi Department of Musculoskeletal Pathology, The Royal Orthopaedic Hospital J. Gregory Department of Orthopaedic Oncology, The Royal Orthopaedic Hospital L. Jeys Department of Orthopaedic Oncology, The Royal Orthopaedic Hospital A. Abudu Department of Orthopaedic Oncology, The Royal Orthopaedic Hospital Aims The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. Conclusion The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0341-2695 44 2 2019 Sacral chordoma: do the width of surgical margin and the use of photon/proton radiotherapy affect local disease control? 381 389 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Tsuda Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Jonathan Stevenson Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Michael Parry Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Lee Jeys Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Purpose Chordoma is a rare but highly aggressive primary bone sarcoma that arises commonly from the sacrum. While en bloc resection has been the mainstay of the treatment, the role of resection margin in millimetres with/without adjuvant radiotherapy (RT) has been unknown. We investigated the prognostic impact of surgical margin width, adjuvant RT, and their combined factor for sacral chordoma. Methods Forty-eight patients who underwent surgical treatment between 1996 and 2016 were studied. Of these, 11 patients (23%) received adjuvant RT; photon RT in 7 (15%) and proton RT in 4 (8%). Margins were microscopically measured in millimetres from the resection surface to the closest tumour on histologic slides. Results The five year and ten year disease-specific survival was 88% and 58%, respectively, and the local recurrence (LR) rate was 48%. The LR rate with 0-mm, < 1.5-mm, and ≥ 1.5-mm margin was 50% (group 1), 50% (group 2: RT－, 61%; group 3: RT+, 14%), and 0% (group 4), respectively. We observed a significantly lower LR rate in patients with adjuvant photon/proton RT (18%) than without it (57%; p = 0.026), and no LR was observed after post-operative proton RT. The combined factor of margin with RT clearly stratified the LR risk: patients of group 1 (positive margin) and 2 (< 1.5-mm margin, RT－) had approximately 7.5× LR risk (p = 0.049) compared with those of group 3 (< 1.5-mm margin, RT+) and 4 (≥ 1.5-mm margin). Conclusion This study identified the lowest risk of local failure in tumour resection with ≥ 1.5-mm margin or negative but < 1.5-mm margin with the use of adjuvant photon/proton radiotherapy for sacral chordoma. Early results of adjuvant proton RT demonstrated excellent local control. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0915-5635 33 2020 Efficacy of low dose rectal diclofenac for preventing post‐endoscopic retrograde cholangiopancreatography pancreatitis: Propensity score‐matched analysis 656 662 EN Takeshi Tomoda Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Eijiro Ueta Department of Gastroenterology and Hepatology, Okayama University Hospital Yuuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Yousuke Saragai Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital Background Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) decreases the incidence of post‐ERCP pancreatitis (PEP). However, the efficacy of low dose rectal NSAIDs for preventing PEP remains controversial. Methods We performed a retrospective study of 301 patients with native papilla and a body weight of <50 kg who underwent ERCP between September 2010 and October 2019. After July 2016, a 25 mg dose of rectal diclofenac was routinely administered within 15 min before ERCP (NSAIDs group, n = 72) and the control group (n = 229) consisted of patients undergoing ERCP before this date without treatment. We compared the incidence of PEP between the two groups using propensity score matching. Results A total of 66 pairs of patients in each group were selected. The patients and procedural‐related factors were similar in both groups. In total, 15 patients (11.4%) developed PEP: 12.1% (8/66) in the NSAIDs group and 10.6% (7/66) in the control group (Odds ratio (OR) 1.2; 95% confidence interval (CI) 0.4–3.5; P = 0.78). There was no significant difference in incidence of other adverse events related to ERCP between the two groups. Conclusions Prophylactic administration of a 25 mg dose of rectal diclofenac did not reduce the incidence of PEP in patients with a native papilla and a body weight of <50 kg in this study and a certain dose of rectal NSAIDs, such as a 100‐mg dose, should be administered regardless of body weight to prevent PEP. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 A Disseminated Fusarium fujikuroi Species Complex Infection Prior to Allogeneic Hematopoietic Stem Cell Transplantation 435 441 EN Keigo Fujishita Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Katsuhiko Kamei Medical Mycology Research Center, Chiba University Katsuma Tani Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuka Fujisawa Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Wataru Kitamura Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Takuya Machida Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Case Report 10.18926/AMO/60805 A 53-year-old man was diagnosed with acute myeloid leukemia, which was refractory to chemotherapies. Systemic papules appeared afterward. The skin biopsies revealed filamentous fungal infection including fusariosis. Despite antifungal therapy, the infection did not resolve, because neutropenia persisted with the leukemia. He underwent hematopoietic stem cell transplantation (HSCT) to overcome the leukemia and restore normal hematopoiesis but died from fusariosis just before engraftment. Fusarium fujikuroi species complex was detected in blood cultures with poor antifungal susceptibility. Because restoring normal hematopoiesis is important in the treatment of fusariosis, HSCT might be considered for patients with persistent pancytopenia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Oblique Surface Dose Calculation in High-Energy X-ray Therapy 415 422 EN Naomasa Narihiro Graduate School of Health Sciences, Department of Radiological Technology, Okayama University Masataka Oita Department of Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshihiro Takeda Graduate School of Health Sciences, Department of Radiological Technology, Okayama University Original Article 10.18926/AMO/60801 During radiation therapy, incident radiation oblique to the skin surface is high and may cause severe skin damage. Understanding the dose of radiation absorbed by the skin is important for predicting skin damage due to radiation. In this study, we used a high-energy (4 MV) X-ray system and an optically stimulated luminescence dosimeter (OSLD) that was developed for personal exposure dosimetry. We determined the dose variation and angular dependence, which are the characteristics of a small OSLD required to derive the calculation formula for the oblique surface dose. The dose variation was determined using the coefficient of variation. The maximum coefficient of variation for 66 small-field OSLDs was 1.71%. The angular dependence, obtained from the dose ratio of the dosimeter in the vertical direction, had a maximum value of 1.37. We derived a new equation in which the oblique surface dose can be calculated within the error range of －7.7-5.1%. No potential conflict of interest relevant to this article was reported.

Nature Acta Medica Okayama 2045-2322 10 1 2020 Transversus Abdominis Plane Block Reduced Early Postoperative Pain after Robot-assisted Prostatectomy: a Randomized Controlled Trial 282 EN Hideki Taninishi Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Matsusaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Analgesic effect of transversus abdominis plane block (TAP block) in lower major abdominal laparoscopic surgery with about 5 cm of maximum surgical scar has been controversial. We hypothesized that TAP block has benefits, so the analgesic effect of TAP block after robot-assisted laparoscopic prostatectomy (RALP) was evaluated. One hundred patients were enrolled in this prospective, double-blinded, randomized study. Standardized general anesthesia with wound infiltration on camera port and fentanyl dose limit of 3 mu g/kg was provided. Ultrasound-guided, single-shot subcostal TAP block with either 0.375% ropivacaine (Ropivacaine group, 48 patients) or normal saline (Control group, 52 patients) was performed by anesthesiologist in charge (34 anesthesiologists) after surgical procedure. Pain score using numerical rating scale (NRS) and postoperative intravenous fentanyl were evaluated for the first 24 postoperative hours. Median values (interquartile range) of NRS scores when the patients were transferred to post-anesthesia care unit (PACU) were 5 (2-7) in Ropivacaine group and 6 (4-8) in Control group at rest (P = 0.03), 5 (2-8) in Ropivacaine group and 7 (5-8) in Control group during movement (P < 0.01). These significant differences disappeared at the time of discharging PACU. Fentanyl doses for the first 24 postoperative hours were 210 mu g (120-360) in Ropivacaine group and 200 mu g (120-370) in Control group (P = 0.79). These results indicated that subcostal TAP block by anesthesiologists of varied level of training reduced postoperative pain immediate after RALP. TAP block had fundamental analgesic effect, but this benefit was too small to reduce postoperative 24-hour fentanyl consumption. No potential conflict of interest relevant to this article was reported.

Remedy Acta Medica Okayama 2474-1647 5 2020 Step-by-Step Procedure to Test Photoelectric Dye-Coupled Polyethylene Film as Retinal Prosthesis to Induce Light-Evoked Spikes in Isolated Retinal Dystrophic Tissue of rd1 Mice 2903 EN Toshihiko Matsuo Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems Keiko Terada Research Center, Techno Pro, Inc. Mikako Sakurai Research Center, Techno Pro, Inc. Shihu Liu Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems Koichiro Yamashita Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Tetsuya Uchida Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Purpose: Multielectrode array recording for electric activity in cardiac and neuronal cells has been developed as preclinical tests for drug screening. This study aims to establish an in vitro assay system, using the multielectrode array, to record light-evoked spikes in isolated degenerative retinal tissues of retinal dystrophic rd1 mouse, as a preclinical test to examine the efficacy of photoelectric dye-coupled thin film retinal prosthesis. Methods: Light-evoked spike response was tested for 1 min at first step in the isolated degenerative retinal tissue of retinal dystrophic rd1 mouse only on the multielectrode array, tested in the same retinal tissue overlain with a plain control film for light-off and light-on 10 min each at second step, and tested in the same tissue overlain with a dye-coupled film at third step. The retinal tissues which showed light-evoked response at first or second step were not used for evaluation at third step. Results: Residual light-evoked spikes were recorded at first or second step in 18 of 35 retinal tissues (51%) at 6 weeks of the age in rd1 mice, 16 of 44 tissues (36%) at 7 weeks, and 10 of 39 tissues (25%) at 8 weeks. At third step, light-evoked spikes were recorded with dye-coupled films in 8 of 17 retinal tissues (47%) at 6 weeks, 10 of 28 tissues (35%) at 7 weeks, and 8 of 29 tissues (27%) at 8 weeks. Conclusion: A step-by-step procedure with internal control was established to measure light-evoked spikes by the multielectrode array in the isolated degenerative retinal tissue to evaluate photoelectric dye-coupled thin films. This preclinical study would present one line of evidence for the efficacy of photoelectric dye-coupled thin film retinal prosthesis towards a first-in-human clinical trial. No potential conflict of interest relevant to this article was reported.

European Society of Surgical Oncology Acta Medica Okayama 0748-7983 47 2 2020 Navigation-assisted pelvic resections and reconstructions for periacetabular chondrosarcomas 416 423 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoichi Kaneuchi Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Jonathan Stevenson Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Michael Parry Vineet Kurisunkal Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Rhys Clark Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Yusuke Tsuda Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Minna Laitinen Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Robert Grimer Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Lee Jeys Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Objectives Survival in patients with chondrosarcomas has not improved over 40 years. Although emerging evidence has documented the efficacy of navigation-assisted surgery, the prognostic significance in chondrosarcomas remains unknown. We aimed to assess the clinical benefit of navigation-assisted surgery for pelvic chondrosarcomas involving the peri-acetabulum. Methods We studied 50 patients who underwent limb-sparing surgery for periacetabular chondrosarcomas performed with navigation (n = 13) without it (n = 37) at a referral musculoskeletal oncology centre between 2000 and 2015. Results The intralesional resection rates in the navigated and non-navigated groups were 8% (n = 1) and 19% (n = 7), respectively; all bone resection margins were clear in the navigated group. The 5-year cumulative incidence of local recurrence was 23% and 56% in the navigated and non-navigated groups, respectively (p = 0.035). There were no intra-operative complications related to use of navigation. There was a trend toward better functional outcomes in the navigated group (mean MSTS score, 67%) than the non-navigated group (mean MSTS score, 60%; p = 0.412). At a mean follow-up of 63 months, the 5-year disease-specific survival was 76% and 53% in the navigated and non-navigated group, respectively (p = 0.085), whilst the 5-year progression-free survival was 62% and 28% in the navigated and non-navigated group, respectively (p = 0.032). Conclusion This study confirmed improved local control and progression-free survival with the use of computer navigation in patients with limb-salvage surgery for periacetabular chondrosarcomas, although the advancement in other treatment modalities is required for improvement of disease-specific survival. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0960-7404 35 2020 Low-grade soft-tissue sarcomas: What is an adequate margin for local disease control? 303 308 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoichi Kaneuchi Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Yusuke Tsuda Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Jonathan Stevenson Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Michael Parry Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Lee Jeys Oncology Service, The Royal Orthopaedic Hospital NHS Foundation Trust Background 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. Methods 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. Results 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). Conclusion 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 The Late Phase/Early Phase Ratio of Pancreatic CT Values as a Novel Predictor of Pancreatic Fistula after Distal Pancreatectomy 351 358 EN Masashi Utsumi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takayuki Yabuki Department of Radiology, National Hospital Organization, Iwakuni Clinical Center Seiichi Nagahisa Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Seitaro Nishimura Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yuta Une Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yuji Kimura Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Megumi Watanabe Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takashi Arataa Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Koh Katsuda Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Kohji Tanakaya Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organization, Iwakuni Clinical Center Original Article 10.18926/AMO/60374 Post-operative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). In this retrospective study, we reviewed the data from patients who underwent DP between 2008 and 2019 in our institute to determine whether the late phase/early phase ratio (L/E ratio) by preoperative computed tomography (CT) scan in the pancreas could predict POPF occurrence after DP. We examined the relationship between preoperative or intraoperative factors and the occurrence of POPF after DP using statistical methods in 23 males and 21 females with a mean age of 73. The mean L/E ratio was significantly lower in the POPF group than the non-POPF group (p=0.035). The L/E ratio had moderate diagnostic accuracy, with a calculated optimal cutoff value of 0.77. In univariate analysis, a significant association was noted between POPF and stump thickness ≥ 16.9, body mass index ≥ 27.5, and L/E ratio ≤ 0.77. In the multivariate analysis, the L/E ratio (odds ratio, 5.96; p=0.036) was an independent risk factor for POPF. Our findings suggest that the pancreatic L/E ratio may predict the occurrence of POPF after DP. This measure may be useful in preoperative risk stratification, patient counseling, and perioperative patient management, improving clinical outcomes after DP. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Recurrence of Solitary Fibrous Tumor/Hemangiopericytoma Could Be Predicted by Ki-67 Regardless of Its Origin 335 343 EN Yumiko Yamamoto Department of Diagnostic Pathology, Kochi University Yoshihiro Hayashi Department of Equipment of Support Planning Office, Kochi University Ichiro Murakami Department of Diagnostic Pathology, Kochi University Original Article 10.18926/AMO/60372 Since the discovery of the NAB2-STAT6 gene fusion in 2013, solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) have been considered the same disease. STAT6 nuclear stain is approved as a highly sensitive and specific marker to diagnose SFT/HPC from other tumors with similar histology. As the next step, detection of fusion variants that may predict clinical malignancy of SFT/HPC has been attempted. However, no fusion variants with a clear relation to malignancy have been identified. In this study, the clinical and histological backgrounds of 23 Japanese patients diagnosed with SFT/HPC from 2000 to 2019 at Kochi University Hospital were examined to identify factors potentially related to recurrence. A significant relationship to recurrence was detected for mitosis ≥ 1/10 HPF (400×), necrosis, and Ki-67>5%. These findings indicate that a deliberate investigation of histological features such as mitosis and necrosis is crucial for the clinical observation of SFT/ HPC patients. In addition, Ki-67 was revealed to be a useful parameter to predict recurrence in SFT/HPC patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Cytotoxic Effects of Alcohol Extracts from a Plastic Wrap (Polyvinylidene Chloride) on Human Cultured Liver Cells and Mouse Primary Cultured Liver Cells 327 334 EN Ken-ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Kagawa Okayama University Hospital Sakae Arimoto Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Xian Wen Tan Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Yasui Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Oshiki Department of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/60371 An increasing accumulation of microplastics and further degraded nanoplastics in our environment is suspected to have harmful effects on humans and animals. To clarify this problem, we tested the cytotoxicity of two types of plastic wrap on human cultured liver cells and mouse primary cultured liver cells. Alcohol extracts from plastic wrap, i.e., polyvinylidene chloride (PVDC), showed cytotoxic effects on the cells. Alcohol extracts of polyethylene (PE) wrap were not toxic. The commercially available PVDC wrap consists of vinylidene chloride, epoxidized soybean oil, epoxidized linseed oil as a stiffener and stabilizer; we sought to identify which component(s) are toxic. The epoxidized soybean oil and epoxidized linseed oil exerted strong cytotoxicity, but the plastic raw material itself, vinylidene chloride, did not. Our findings indicate that plastic wraps should be used with caution in order to prevent health risks. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Relationship Between Partial Carbon Dioxide Pressure and Strong Ions in Humans: A Retrospective Study 319 325 EN Satoshi Isoyama Department of Anesthesiology and Resuscitation, Okayama University Hospital Satoshi Kimura Department of Anesthesiology and Resuscitation, Okayama University Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitation, Okayama University Hospital Original Article 10.18926/AMO/60370 Little is known about the role of a strong ions in humans with respiratory abnormalities. In this study, we investigated the associations between partial carbon dioxide pressure (pCO2) and each of sodium ion (Na+) concentrations, chloride ion (Cl－) concentrations and their difference (SIDNa-Cl). Blood gas data were obtained from patients in a teaching hospital intensive care unit between August 2013 and January 2017. The association between pCO2 and SIDNa-Cl was defined as the primary outcome. The associations between pCO2 and [Cl－], [Na+] and other strong ions were secondary outcomes. pCO2 was stratified into 10 mmHg-wide bands and treated as a categorical variable for comparison. As a result, we reviewed 115,936 blood gas data points from 3,840 different ICU stays. There were significant differences in SIDNa-Cl, [Cl－], and [Na+] among all categorized pCO2 bands. The respective pCO2 SIDNa-Cl, [Cl－], and [Na+] correlation coefficients were 0.48, －0.31, and 0.08. SIDNa-Cl increased and [Cl－] decreased with pCO2, with little relationship between pCO2 and [Na+] across subsets. In conclusion, we found relatively strong correlations between pCO2 and SIDNa-Cl in the multiple blood gas datasets examined. Correlations between pCO2 and chloride concentrations, but not sodium concentrations, were further found to be moderate in these ICU data. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Immobility-reducing Effects of Ketamine during the Forced Swim Test on 5-HT1A Receptor Activity in the Medial Prefrontal Cortex in an Intractable Depression Model 301 306 EN Kei Takahashi Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ushio Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/60368 Ketamine has been clinically proven to ameliorate depression, including treatment-resistant depression. The detailed mechanism of action of ketamine in treatment-resistant depression remains unclear. We examined the effects of ketamine on the immobility times of adrenocorticotropic hormone (ACTH)-treated rats during the forced swim test, and we explored the mechanism by which ketamine acts in this model. We investigated the neuroanatomical site of action by microinjecting ketamine into the medial prefrontal cortex of rats. A significant reduction of the rats’ immobility during the forced swim test was observed after the intraperitoneal injection of ketamine in both saline- and ACTH-treated rats. The microinjection of ketamine into the medial prefrontal cortex also decreased immobility during the forced swim test in both saline- and ACTH-treated rats. The immobility-decreasing effect of intraperitoneally injected ketamine was blocked by administering WAY100635, a 5-HT1A receptor antagonist, into the medial prefrontal cortex. These findings contribute to the evidence that ketamine can be useful against treatment-resistant depressive conditions. The immobility-reducing effects of ketamine might be mediated by 5-HT1A receptor activity in the medial prefrontal cortex. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Factors Predicting a Favorable Disease Course Without Anti-TNF Therapy in Crohn’s Disease Patients 265 274 EN Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Yasutomi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Oka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Kinugasa Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahar Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Harada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Kato bDepartment of Gastroenterology, Mitsui Memorial Hospital Original Article 10.18926/AMO/60363 Determining factors that predict a favorable disease course without anti-tumor necrosis factor (TNF) agents would help establish a more cost-effective strategy for Crohn’s disease (CD). A retrospective chart review was performed for CD patients with disease durations > 10 years who had not received anti-TNF agents as first-line therapy. Patients were divided into 2 groups: those who received neither anti-TNF agents nor bowel resection (G1), and those who had received an anti-TNF agent and/or bowel resection (G2). The patient backgrounds, therapies and clinical courses were compared between the groups. A total of 62 CD patients met the inclusion criteria (males: 71%; median duration of follow-up: 19 years). Six patients were included in G1; they were significantly less likely to have upper gastrointestinal lesions than G2 (p=0.007). A multivariate analysis revealed that the significant factors for avoidance of bowel resection without anti-TNF treatment were non-stricturing and non-penetrating behaviors, and absence of upper gastrointestinal lesions at the diagnosis (hazard ratios 0.41 and 0.52; p=0.004 and 0.04, respectively). In consideration of the long treatment course of CD, patients with non-stricturing and non-penetrating behaviors and no upper gastrointestinal lesions should not be treated with anti-TNF agents as first-line therapy. No potential conflict of interest relevant to this article was reported.

Nature Acta Medica Okayama 2045-2322 10 1 2020 The role of RND-type efflux pumps in multidrug-resistant mutants of Klebsiella pneumoniae 10876 EN Rui Ting Ni Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoyasu Onishi Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minako Mizusawa Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryoko Kitagawa Department of Microbiology, Faculty of Pharmaceutical Sciences,Okayama University Takanori Kishino Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Futoshi Matsubara Department of Microbiology and Biochemistry, Daiichi University of Pharmacy Tomofusa Tsuchiya Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teruo Kuroda Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Wakano Ogawa Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The emergence of multidrug-resistant Klebsiella pneumoniae is a worldwide problem. K. pneumoniae possesses numerous resistant genes in its genome. We isolated mutants resistant to various antimicrobials in vitro and investigated the importance of intrinsic genes in acquired resistance. The isolation frequency of the mutants was 10(-7)-10(-9). Of the multidrug-resistant mutants, hyper-multidrug-resistant mutants (EB256-1, EB256-2, Nov1-8, Nov2-2, and OX128) were identified, and accelerated efflux activity of ethidium from the inside to the outside of the cells was observed in these mutants. Therefore, we hypothesized that the multidrug efflux pump, especially RND-type efflux pump, would be related to changes of the phenotype. We cloned all RND-type multidrug efflux pumps from the K. pneumoniae genome and characterized them. KexEF and KexC were powerful multidrug efflux pumps, in addition to AcrAB, KexD, OqxAB, and EefABC, which were reported previously. It was revealed that the expression of eefA was increased in EB256-1 and EB256-2: the expression of oqxA was increased in OX128; the expression of kexF was increased in Nov2-2. It was found that a region of 1,485 bp upstream of kexF, was deleted in the genome of Nov2-2. K. pneumoniae possesses more potent RND-multidrug efflux systems than E. coli. However, we revealed that most of them did not contribute to the drug resistance of our strain at basic levels of expression. On the other hand, it was also noted that the overexpression of these pumps could lead to multidrug resistance based on exposure to antimicrobial chemicals. We conclude that these pumps may have a role to maintain the intrinsic resistance of K. pneumoniae when they are overexpressed. The antimicrobial chemicals selected many resistant mutants at the same minimum inhibitory concentration (MIC) or a concentration slightly higher than the MIC. These results support the importance of using antibiotics at appropriate concentrations at clinical sites. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 2050-7526 8 22 2020 Synthesis of [7]phenacene incorporating tetradecyl chains in the axis positions and its application in field-effect transistors 7422 7435 EN Hideki Okamoto Graduate School of Natural Science and Technology, Okayama University Shino Hamao Research Institute for Interdisciplinary Science, Okayama University Keiko Kozasa Graduate School of Natural Science and Technology, Okayama University Yanan Wang Research Institute for Interdisciplinary Science, Okayama University Yoshihiro Kubozono Research Institute for Interdisciplinary Science, Okayama University Yong-He Pan Department of Physics & Center for Quantum Technology, National Tsing Hua University Yu-Hsiang Yen Department of Physics & Center for Quantum Technology, National Tsing Hua University Germar Hoffmann Department of Physics & Center for Quantum Technology, National Tsing Hua University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Kenta Goto Institute for Materials Chemistry and Engineering, Kyushu University Field-effect transistors (FETs) were fabricated using a new type of phenacene molecule, 3,12-ditetradecyl[7]phenacene ((C14H29)2-[7]phenacene), and solid gate dielectrics or an electric double layer (EDL) capacitor with an ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate (bmim[PF6])). The new molecule, (C14H29)2-[7]phenacene, was efficiently synthesized via the Mallory photoreaction. Its crystal structure and electronic properties were determined, using X-ray diffraction, scanning tunneling microscopy/spectroscopy (STM and STS), absorption spectroscopy, and photoelectron yield spectroscopy, which showed a monoclinic crystal lattice (space group P21 (no. 4)) and an energy gap of ∼3.0 eV. The STM image clearly showed the molecular structure of (C14H29)2-[7]phenacene, as well as the closed molecular stacking, indicative of a strong fastener effect between alkyl chains. The X-ray diffraction pattern of thin films of (C14H29)2-[7]phenacene formed on a SiO2/Si substrate suggested that the molecule stood on the surface with an inclined angle of 30° with respect to the normal axis of the surface. The FET properties were recorded in two-terminal measurement mode, showing p-channel normally-off characteristics. The averaged values of field-effect mobility, μ, were 1.6(3) cm2 V－1 s－1 for a (C14H29)2-[7]phenacene thin-film FET with a SiO2 gate dielectric and 6(4) × 10－1 cm2 V－1 s－1 for a (C14H29)2-[7]phenacene thin-film EDL FET with bmim[PF6]. Thus, higher FET performance was obtained with an FET using a thin film of (C14H29)2-[7]phenacene compared to parent [7]phenacene. This study could pioneer an avenue for the realization of high-performance FETs through the addition of alkyl chains to phenacene molecules. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1746-160X 16 1 2020 Occlusal reconstruction of a patient with ameloblastoma ablation using alveolar distraction osteogenesis: a case report 12 EN Yoshihito Ishihara Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hikaru Arakawa Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Akiyoshi Nishiyama Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Ameloblastoma is one of the most common benign odontogenic neoplasms. Its surgical excision has the potential to lead to postoperative malocclusion. In this case report, we describe the successful interdisciplinary orthodontic treatment of a patient with ameloblastoma who underwent marginal mandibulectomy. Case presentation A woman of 20-year-old was diagnosed with ameloblastoma, and underwent marginal mandibulectomy when she was 8 years of age. She had an excessive overjet (11.5 mm) and a mild open bite (- 1.5 mm) with a severely resorbed atrophic edentulous ridge in the area around the mandibular left lateral incisor, canine and first premolar. An alveolar bone defect associated with tumor resection was regenerated by vertical distraction osteogenesis (DO). Subsequently, 3 dental implants were placed into the reconstructed mandible. Orthodontic treatment using implant-anchored mechanics provided a proper facial profile with significantly improved occlusal function. The occlusion appeared stable for a 7-year retention period. Conclusions These results suggest that surgically assisted and implant anchored-orthodontic approaches might be effective for the correction of such malocclusions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Serum REIC/Dickkopf-3 Protein Level Predicts Disease-Free Survival in Patients with Hepatocellular Carcinoma 237 243 EN Atsushi Oyama Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Sawahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kato Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/59957 The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Formulas to Estimate Appropriate Surgical Amounts of Unilateral Recession-Resection in Intermittent Exotropia with Distance-Near Disparity 229 236 EN Kiyo Shibata Department of Ophthalmology, Okayama University Hospital Ichiro Hamasaki Department of Ophthalmology, Okayama University Hospital Shinji Toshima Department of Ophthalmology, Kurashiki Medical Center Takehiro Shimizu Department of Ophthalmology, Okayama University Hospital Reika Kono Department of Ophthalmology, Okayama University Hospital Manabu Miyata Department of Ophthalmology and Visual Sciences Kyoto University Graduate School of Medicine Shin Morisawa Department of Ophthalmology, Kawasaki Medical School General Medical Center Takashi Furuse Department of Ophthalmology, Okayama Saiseikai General Hospital Satoshi Hasebe Department of Ophthalmology, Okayama Saiseikai General Hospital Hiroshi Ohtsuki Department of Ophthalmology, Okayama Saiseikai General Hospital Yuki Morizane Department of Ophthalmology, Okayama University Hospital Fumio Shiraga Department of Ophthalmology, Okayama University Hospital Original Article 10.18926/AMO/59956 The purpose of this study was to derive new formulas to provide an optimal surgical procedure and optimal amount of recession-resection (RR) surgery in intermittent exotropia (IXT) with a disparity in angle of deviation depending on the fixation distance. The records of 117 consecutive patients with IXT who underwent RR surgery between March 2008 and December 2011 at Okayama University Hospital were retrospectively examined. Multivariable linear regression analysis was performed using the observed corrective angle of deviation at distance or near fixation as the dependent variable, and amounts of lateral rectus muscle (LR) recession (mm) and medial rectus muscle (MR) resection, and age at surgery (years) as independent variables. Two simultaneous formulas were derived: corrective angle of deviation at distance fixation (°)=1.8×recession (mm)+1.6× resection (mm)+0.15×age (years)–6.6, and corrective angle at near fixation (°)=1.5×recession (mm)+1.7× resection (mm)+0.18×age (years)–3.8. Comparisons of coefficient values of the formulas between distance and near fixation revealed that LR recession was more affected by the corrective angle in distance than near fixation. MR resection was more affected at near than distance fixation. We found that our new formulas estimated the appropriate amount of unilateral RR surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Stem Cell Therapy in Heart Disease: Limitations and Future Possibilities 185 190 EN Toshikazu Sano Department of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San Francisco Shuta Ishigami Department of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San Francisco Tatsuo Ito Department of Hygiene, Kawasaki Medical University Shunji Sano Department of Surgery, Division of Pediatric Cardiothoracic Surgery, University of California San Francisco Review 10.18926/AMO/59948 Heart diseases are one of the major causes of morbidity and mortality worldwide. Despite major advances in drug and interventional therapies, surgical procedures, and organ transplantation, further research into new therapeutic options is still necessary. Stem cell therapy has emerged as one option for the treatment of a variety of heart diseases. Although a large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach, the results obtained from these clinical studies are inconsistent, and stem cell-based improvements of heart performance and cardiac remodeling were found to be quite limited. Since the precise mechanisms underlying the therapeutic actions of stem cells are still under debate, researchers have developed a variety of strategies to improve and boost the potency of stem cells in repair. In this review, we summarize both the current therapeutic strategies using stem cells and future directions for enhancing stem cell potency. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 8 7 2020 Vision loss, tractional retinal detachment, and profound anemia due to rectal carcinoma 1304 1305 EN Akira Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Profound anemia can cause severe proliferative retinopathy and tractional retinal detachment; therefore, it is important to closely investigate the cause of anemia. Endoscopy and computed tomography are valuable tools for this purpose. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 10 2020 Association between maternal periodontal status and ultrasonographic measurement of fetal growth: A longitudinal study EN Ayano Taniguchi-Tabata Department of Preventive Dentistry, Okayama University Hospital Noriko Takeuchi Department of Preventive Dentistry, Okayama University Hospital Yoko Uchida Department of Preventive Dentistry, Okayama University Hospital Daisuke Ekuni Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Morita Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The aim of this prospective cohort study was to investigate the association between intrauterine fetal growth patterns and periodontal status in pregnant women. Fifty-three pregnant women were recruited. Periodontitis was diagnosed based on probing pocket depth and clinical attachment level. Maternal urinary 8-hydroxy-2'-deoxyguanosine levels and body mass index were recorded. Ultrasonographic measurements of the biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) were recorded, and estimated fetal weight (EFW) was calculated. In addition, approximation spline curves of BPD, AC, FL, and EFW were obtained throughout the gestation period. Recorded delivery outcomes were gestational age (GA), birth weight and length, sex, placental weight, and umbilical cord length. Forty-four participants (34.1 +/- 4.9 years) were analyzed. Mean neonatal birth weight was 2906.0 +/- 544.4g. On multiple regression analysis, birth weight was related with periodontitis (standardized beta=-0.21, P=0.001). For EFW and BPD, the curves of the periodontitis group were located lower than those of the non-periodontitis group, with significant differences after 32 weeks and 20 weeks of GA, respectively. In conclusion, periodontal treatment before conception may be recommended and a good periodontal condition in the early stage of pregnancy at the latest is desirable for infant growth. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 09302794 2020 Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure EN Takeshi Tomoda Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Eijiro Ueta Department of Gastroenterology and Hepatology, Okayama University Hospital Yuuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Yousuke Saragai Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke chida Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki atsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital Background To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. Methods A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. Results The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5–43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. Conclusion Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy. Endoscopic biliary stent placement with endoscopic retrograde cholangiography (ERCP) for the treatment of malignant biliary obstruction (MBO) has been widely accepted as an effective drainage method because it is less invasive and safe and has a high success rate (1–3). However, MBO is treated using percutaneous transhepatic biliary drainage (PTBD) or surgical bypass because of difficulties related to endoscopic access to the bile duct following gastrointestinal reconstruction. However, these methods are associated with marked adverse event (AE) rates [1,2,3]. Recently, balloon-assisted endoscopy (BAE) facilitates ERCP in patients with surgically altered anatomy. As for a double-balloon enteroscope (DBE), a short-type DBE (sDBE) is especially useful because it allows the use of many standard ERCP accessories. The success rates of reaching the target site and ERCP-related interventions associated using these endoscopes range from 73–100% and 85–100%, respectively [4, 5]. We previously reported that the success rate of reaching the target site and biliary intervention was 93.8% and 95.7%, respectively, in patients with benign hepaticojejunostomy (HJ) anastomotic stricture [6]. However, inaccessibility of the target site may occur due to severe postoperative adhesions or a long insertion time (i.e., > 60 min). Furthermore, previous reports have shown that the success rate of BAE in MBO cases was significantly lower than that in benign biliary diseases [7, 8]. Few reports have investigated the outcome of BAE for MBO in patients with surgically altered anatomy. Additionally, the risk factors for clinical failure are not well-established. Thus, we retrospectively evaluated the outcomes of endoscopic treatment for MBO using sDBE in patients with surgically altered anatomy and identified risk factors for clinical failure. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2020 Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer EN Saori Yoshida Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 2051-5960 8 1 2020 Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma 42 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomotsugu Ichikawa Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiko Kurozumi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsushi Fujimura Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Fujii Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Tomita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuhiko Hattori Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuhito Uneda Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobushige Tsuboi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keisuke Kaneda Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keigo Makino Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2-STAT3-OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2-STAT3-OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Incarcerated Amyand’s Hernia 171 174 EN Atsushi Okita Department of Surgery, Yakage Town National Health Insurance Hosptial Osamu Yoshida Department of Surgery, Yakage Town National Health Insurance Hosptial Masakazu Murakami Department of Surgery, Yakage Town National Health Insurance Hosptial Case Report 10.18926/AMO/58277 A 76-year-old Japanese man was transferred to our hospital to undergo rehabilitation after traffic accident-related injuries. Seven days post-admission, he presented with abdominal pain and an 8-cm lump in the right inguinal region. He was diagnosed with an incarcerated inguinal hernia and underwent elective surgery the day after manual reduction. He had a normal vermiform appendix which was observed to have adhered to the right indirect hernia sac. An appendectomy and hernia repair using lightweight mesh were performed. We discuss the surgical management of this rare incarcerated Amyand’s hernia and the relevant literature. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Juvenile Granulosa Cell Tumor with an Unusual Clinical Course: A Late-onset and Late Recurrent Case 159 163 EN Thar Htet San Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Ota Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Fushimi Department of Pathology, Himeji Red Cross Hospital Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Hospital Hiroko Toda Section of Diagnostic Pathology, Fukuyama Medical Association Tadayoshi Kunitomo Department of Pathology, Kurashiki Medical Center Keisuke Kodama Department of Gynecology, Kurashiki Medical Center Akihiro Matsukawa Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/58275 Juvenile granulosa cell tumors (JGCTs) are rare ovarian tumors with overall good prognoses. They differ from adult granulosa cell tumors (AGCTs), which are well known for late recurrence. Most JGCTs (～97%) occur in individuals <30 years old. We report a recurrent JGCT in a 40-year-old woman 5 years after initial presentation. The histological appearance and lack of 402C>G missense point mutation of FOXL2 gene (characteristic of AGCT but absent in JGCT) allowed differentiation from AGCT. This is the first comprehensive report of JGCT with late recurrence. Although rare, late recurrence of JGCT can occur; long-term surveillance is suggested. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Non-traumatic Atypical Peri-implant Femoral Fracture at the Distal Screw after Short Femoral Nail Fixation for a Pertrochanteric Fracture 151 157 EN Norio Yamamoto Department of Orthopedic Surgery, Unnan City Hospital Tomoyuki Dan’ura Department of Orthopedic Surgery, Unnan City Hospital Tomoyuki Noda Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/58274 This is the second report of an atypical peri-implant femoral fracture occurring at the distal screw after intramedullary nail fixation of a pertrochanteric fracture. A 94-year-old Japanese female with a 5-year history of alendronate intake presented with prodromal pain in her right thigh after intramedullary nail fixation. Plain radiographs showed an incomplete noncomminuted transverse fracture at the distal screw, suggesting an atypical peri-implant femoral fracture. The pathogenesis of an atypical peri-implant femoral fracture could be a combined systemic bone metabolism disorder and repetitive overloading at the screw, similar to the pathogenesis of an atypical periprosthetic femoral fracture around stem implantation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Association between Histological Types and Enhancement of Dynamic CT for Primary Lung Cancer 129 135 EN Shogo Fukuma Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayoshi Shinya Department of Radiology, Okayama University Hospital Junichi Soh Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichiro Fukuhara Department of Pediatric Radiology, Okayama University Hospital Nanako Ogawa Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Okayama City General Medical Center Takehiro Tanaka Department of Pathology, Okayama University Hospital Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Takao Hiraki Department of Radiology, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, Okayama University Hospital Original Article 10.18926/AMO/58271 The aim of this study was to explore enhancement patterns of different types of primary lung cancers on 2-phase dynamic computed tomography (CT). This study included 217 primary lung cancer patients (141 adenocarcinomas [ADs], 48 squamous cell carcinomas [SCCs], 20 small cell lung carcinomas [SCLCs], and 8 others) who were examined using a 2-phase dynamic scan. Regions of interest were identified and mean enhancement values were calculated. After excluding the 20 SCLCs because these lesions had different clinical stages from the other cancer types, the mean attenuation values and subtractions between phases were compared between types of non-small cell lung carcinomas (NSCLCs) using the Kruskal–Wallis test. Late phase attenuation and attenuation of the late minus unenhanced phase (LMU) of SCCs were significantly higher than those of ADs (p<0.05). To differentiate SCC and AD in the late phase, a threshold of 80.21 Hounsfield units (HU) gave 52.9% accuracy. In LMU, a threshold of 52.16 HU gave 59.3% accuracy. Dynamic lung CT has the potential to aid in differentiating among NSCLC types. No potential conflict of interest relevant to this article was reported.

Hindawi Acta Medica Okayama 0896-4327 2020 2020 Clinical Significance of Septal Malalignment for Transcatheter Closure of Atrial Septal Defect 6090612 EN Yoichi Takaya Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Teiji Akagi Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Nobuhisa Watanabe Division of Medical Support, Okayama University Hospital Norihisa Toh Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine,Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Background. Septal malalignment is related to erosion and device embolization in transcatheter closure of atrial septal defect (ASD), but limited information is available. Objectives. This study aimed to assess clinical significance of septal malalignment and to determine appropriate evaluation of ASD diameter, including the selection of device size. Methods. Four hundred and seventeen patients with ASD who underwent transcatheter closure were enrolled. Septal malalignment was defined as separation between the septum primum and the septum secundum on transesophageal echocardiography. Results. One hundred and eighty-four patients had septal malalignment. The frequency of septal malalignment increased with age reaching around 50% in adult patients. Septal malalignment was related to aortic rim deficiency. The distance of separation between the septum primum and the septum secundum was 5 +/- 2 mm (range, 1-11 mm). In patients with septal malalignment, the ASD diameter measured at the septum primum was 19 +/- 6 mm, while the ASD diameter measured at the septum secundum was 16 +/- 6 mm. There was a difference of 4 +/- 2 mm (range, 0-8 mm) between the ASD diameter measured at the septum primum and that measured at the septum secundum. For transcatheter closure, the Amplatzer Septal Occluder device size 2-3 mm larger and the Occlutech Figulla Flex II device size 4-7 mm larger than the ASD diameter measured at the septum primum were frequently used. During the study period, erosion or device embolization did not occur in all of the patients. Conclusions. Septal malalignment is highly prevalent in adult patients with aortic rim deficiency. The measurement of ASD diameter at the septum primum can be valuable for the selection of device size in patients with septal malalignment. No potential conflict of interest relevant to this article was reported.

SpringerOpen Acta Medica Okayama 2198-7793 6 1 2020 Recurring radiation-induced angiosarcoma of the breast that was treated with paclitaxel chemotherapy: a case report 25 EN Yoko Suzuki Department of Breast and Endocrine surgery in Okayama University Japan Hospital Kohei Taniguchi Department of Pathological diagnosis, Okayama University Japan Hospital Minami Hatono Department of Breast and Endocrine surgery in Okayama University Japan Hospital Yukiko Kajiwara Department of Breast and Endocrine surgery in Okayama University Japan Hospital Yuko Abe Department of Breast and Endocrine surgery in Okayama University Japan Hospital Kengo Kawada Department of Breast and Endocrine surgery in Okayama University Japan Hospital Takahiro Tsukioki Department of Breast and Endocrine surgery in Okayama University Japan Hospital Mariko Kochi Department of Breast and Endocrine surgery in Okayama University Japan Hospital Keiko Nishiyama Department of Breast and Endocrine surgery in Okayama University Japan Hospital Takayuki Iwamoto Department of Breast and Endocrine surgery in Okayama University Japan Hospital Hirokuni Ikeda Department of Breast and Endocrine surgery in Okayama University Japan Hospital Tadahiko Shien Department of Breast and Endocrine surgery in Okayama University Japan Hospital Naruto Taira Department of Breast and Endocrine surgery in Okayama University Japan Hospital Masahiro Tabata Department of Hematology, Oncology, Respiratory, and Allergy Medicine, Okayama University Japan Hospital Hiroyuki Yanai Department of Pathological diagnosis, Okayama University Japan Hospital Hiroyoshi Doihara Department of Breast and Endocrine surgery in Okayama University Japan Hospital Background Angiosarcoma of the breast is very rare and can be divided into primary and secondary angiosarcoma. Radiation-induced angiosarcoma (RIAS) is classified as secondary angiosarcoma. Diagnosis of RIAS is difficult due to its rarity, and the interpretation of pathological imaging is complicated. In the National Comprehensive Care Network (NCCN) guidelines, the first choice of treatment is surgery with negative margins. Adjuvant radiotherapy (RT) for close soft tissue margins should be considered. Preoperative or adjuvant chemotherapy of nonmetastatic disease is not recommended for angiosarcoma. We report a case of RIAS, which was impossible to diagnose with core needle biopsy (CNB) but was diagnosed by excisional biopsy. The patient was then administered adjuvant chemotherapy using conjugated paclitaxel (PTX). Case presentation A 62-year-old woman noticed a tumor in her right breast. She had a history of right breast cancer and had undergone breast-conserving surgery, RT, and tamoxifen therapy 8 years previously. CNB, which was performed twice, was inconclusive. The tumor was surgically excised and pathological analysis yielded a diagnosis of angiosarcoma. She then underwent a right mastectomy. One month after she underwent right mastectomy, a nodule reappeared on the skin of her right breast, and excisional biopsy revealed recurrence of angiosarcoma. A few weeks later another nodule reappeared near the post-operative scar and excisional biopsy revealed recurrence of angiosarcoma. We assumed that surgical therapy was insufficient because the patient experienced relapse of angiosarcoma after complete mastectomy. After the second recurrence, we treated her with systemic chemotherapy using PTX. There was no evidence of recurrence 8 months after chemotherapy. Conclusion Although angiosarcoma is difficult to diagnose, many patients have a poor prognosis. Therefore, prompt treatment intervention is desired. Moreover, there is little evidence regarding adjuvant therapy of angiosarcoma since it is a rare disease. We consider that adjuvant therapy helped to effectively prevent recurrence in the patient after complete excision. No potential conflict of interest relevant to this article was reported.

Japan Epidemiological Association Acta Medica Okayama 0917-5040 30 4 2020 Causal Diagrams: Pitfalls and Tips 153 162 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Shinozaki Department of Information and Computer Technology, Faculty of Engineering, Tokyo University of Science Eiji Yamamoto Okayama University of Science Graphical models are useful tools in causal inference, and causal directed acyclic graphs (DAGs) are used extensively to determine the variables for which it is sufficient to control for confounding to estimate causal effects. We discuss the following ten pitfalls and tips that are easily overlooked when using DAGs: 1) Each node on DAGs corresponds to a random variable and not its realized values; 2) The presence or absence of arrows in DAGs corresponds to the presence or absence of individual causal effect in the population; 3) "Non-manipulable" variables and their arrows should be drawn with care; 4) It is preferable to draw DAGs for the total population, rather than for the exposed or unexposed groups; 5) DAGs are primarily useful to examine the presence of confounding in distribution in the notion of confounding in expectation; 6) Although DAGs provide qualitative differences of causal structures, they cannot describe details of how to adjust for confounding; 7) DAGs can be used to illustrate the consequences of matching and the appropriate handling of matched variables in cohort and case-control studies; 8) When explicitly accounting for temporal order in DAGs, it is necessary to use separate nodes for each timing; 9) In certain cases, DAGs with signed edges can be used in drawing conclusions about the direction of bias; and 10) DAGs can be (and should be) used to describe not only confounding bias but also other forms of bias. We also discuss recent developments of graphical models and their future directions. No potential conflict of interest relevant to this article was reported.

SpringerOpen Acta Medica Okayama 2226-4108 8 4 2019 Effects of loading contact on electric-power generation of lead zirconate titanate piezoelectric ceramic plate 509 518 EN Mitsuhiro Okayasu Graduate School of Natural Science and Technology, Okayama University Tsukasa Ogawa Graduate School of Natural Science and Technology, Okayama University To better understand the generation of electric power for piezoelectric PbZrTiO3 (PZT) ceramic plate (phi 25 mm), an attempt was made to investigate experimentally and numerically electric-power generation characteristics during cyclic bending under various loading fixtures (phi 0-phi 20 mm), i.e., different contact areas. Increasing the load-contact area on the PZT ceramic leads to a nonlinear decrease in the generated voltage. Decreasing contact area basically enhances the generated voltage, although the voltage saturates during loading when the contact area is less than phi 5 mm. A similar voltage is generated for phi 0 and phi 5 mm, which is attributed to strain status (ratio of compressive and tensile strain) and material failure due to different stress distribution in the PZT ceramic. On the basis of the obtained electric generation voltage, suitable loading conditions are clarified by loading with the phi 5 mm fixture, which generates a higher voltage and a longer lifetime of the PZT ceramic. From this approach, it is appeared that the area contact with the area ratio of 0.04 (phi 5 mm/phi 20 mm) is suitable to obtain the high efficiency of the electric voltage. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 Metabolic Profiling of the Cerebrospinal Fluid in Pediatric Epilepsy 65 72 EN Tomoyuki Akiyama Department of Child Neurology, Okayama University Hospital Daisuke Saigusa Tohoku Medical Megabank Organization, Tohoku University Yuki Hyodo Department of Child Neurology, Okayama University Hospital Keiko Umeda Tohoku Medical Megabank Organization, Tohoku University Reina Saijo Tohoku Medical Megabank Organization, Tohoku University Seizo Koshiba Tohoku Medical Megabank Organization, Tohoku University Katsuhiro Kobayashi Department of Child Neurology, Okayama University Hospital Original Article 10.18926/AMO/57955 To characterize metabolic profiles within the central nervous system in epilepsy, we performed gas chromatography-tandem mass spectrometry (GC-MS/MS)-based metabolome analysis of the cerebrospinal fluid (CSF) in pediatric patients with and without epilepsy. The CSF samples obtained from 64 patients were analyzed by GC-MS/MS. Multivariate analyses were performed for two age groups, 0-5 years of age and 6-17 years of age, to elucidate the effects of epilepsy and antiepileptic drugs on the metabolites. In patients aged 0-5 years (22 patients with epilepsy, 13 without epilepsy), epilepsy patients had reduced 2-ketoglutaric acid and elevated pyridoxamine and tyrosine. In patients aged 6-17 years (12 with epilepsy, 17 without epilepsy), epilepsy patients had reduced 1,5-anhydroglucitol. Valproic acid was associated with elevated 2-aminobutyric acid, 2-ketoisocaproic acid, 4-hydroxyproline, acetylglycine, methionine, N-acetylserine, and serine. Reduced energy metabolism and alteration of vitamin B6 metabolism may play a role in epilepsy in young children. The roles of 1,5-anhydroglucitol in epilepsy in older children and in levetiracetam and zonisamide treatment remain to be explained. Valproic acid influenced the levels of amino acids and related metabolites involved in the metabolism of serine, methionine, and leucine. No potential conflict of interest relevant to this article was reported.