MDPI AG Acta Medica Okayama 1422-0067 27 5 2026 Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model 2308 EN Yoshihiro Matsuda Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Takezaki Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuma Sakamoto Department of Immunology and Molecular Genetics, Kawasaki Medical School Nobuyasu Baba Department of Immunology and Molecular Genetics, Kawasaki Medical School Masanori Iseki Department of Immunology and Molecular Genetics, Kawasaki Medical School Yoshio Kawakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsushi Shiomi Department of Pathology, Kawasaki Medical School Tomoyuki Mukai Department of Immunology and Molecular Genetics, Kawasaki Medical School Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2056-5933 12 1 2026 Dental infection is associated with early relapse in patients with ANCA-associated vasculitis e006392 EN Shoichi Nawachi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshia Miyawaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Moe Sakamoto-Tokunaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Terajima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuya Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Hirose Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takato Nakadoi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manami Hirata-Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Hayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruki Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eri Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Takano-Narazaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigetomo Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Matsumoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-Ei Sada 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 Objectives Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease where infections can trigger relapses. Dental infections, being common and associated with systemic inflammation, may play a role in AAV relapse, though their impact remains unclear. We aimed to evaluate the association between severe dental infections and early relapse in patients with AAV.<br> Methods This retrospective cohort study included patients newly diagnosed with AAV between January 2011 and July 2022. Patients with severe dental infections requiring tooth extraction were placed in the dental infection group, while the remaining patients were assigned to the control group. The primary outcome was defined as either vasculitis relapse or all-cause mortality within 1 year of treatment initiation. Adjusted HRs (aHRs) and 95% CIs were estimated using Cox proportional hazards models.<br> Results A total of 93 patients were enrolled with a median age of 74 years. 41 patients (44.1%) had severe dental infections in this cohort. Over the 1-year follow-up period, 13 patients experienced a relapse and two died, resulting in a composite event rate of 20.9 per 100 person-years. Dental infection was independently associated with the composite outcome (aHR, 3.78 (95% CI 1.13 to 12.66); p=0.031). Exploratory analysis indicated that composite outcome rates were similar regardless of tooth extraction among patients with dental infections.<br> Conclusions Severe dental infections were associated with increased risk of early relapse or mortality in AAV. These findings highlight the importance of early dental evaluation in AAV management. No potential conflict of interest relevant to this article was reported.

The Carbon Society of Japan Acta Medica Okayama 2436-5831 4 3 2025 Synthesis and applications of porous carbonaceous materials with inherited molecular structural features from the precursor molecules 179 187 EN Koki Chida Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Takeharu Yoshi Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Kazuhide Kamiya Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, The University of Osaka Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Fumito Tani Institute for Materials Chemistry and Engineering, Kyushu University Tomoki Ogoshi Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Hirotomo Nishihara Institute of Multidisciplinary Research for Advanced Materials, Tohoku University The carbonization of organic crystalline materials, such as metal organic frameworks and covalent organic frameworks, has emerged as a promising approach for producing functional porous carbonaceous materials. However, both the chemically defined long-term ordered structures and the local chemical structures derived from these precursor materials are generally lost, resulting in amorphous carbons. As a result, controlling the molecular-level structure of nanoporous carbons remains a significant challenge. We report a new bottom-up synthesis approach for porous carbons with a molecular-level design, involving the carbonization of well-designed precursor molecules by thermal polymerization. Among the resulting carbons, ordered carbonaceous frameworks, which contain a high-density of regularly aligned single-atomic metal species, have been identified as promising platforms for single-atom catalysts. This approach also enables the synthesis of various three-dimensional porous carbons that reflect the structural features of their precursor molecules. Recent progress in the synthesis and applications of porous carbons derived from molecular precursors is summarized, highlighting their potential for the development of functional materials. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2752-6542 5 1 2025 Chloroplast heat shock protein cpHsc70-1 interacts with thylakoid membrane remodeling protein VIPP1 C-terminal tail and controls VIPP1 oligomer assembly pgaf393 EN Di Li Institute of Plant Science and Resources, Okayama University Sarah Wanjiru Gachie Institute of Plant Science and Resources, Okayama University Shin-ichiro Ozawa Institute of Plant Science and Resources, Okayama University Martin Scholz Institute of Plant Biology and Biotechnology, University of Münster Michael Hippler Institute of Plant Science and Resources, Okayama University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Oxygenic photosynthetic organisms depend on the thylakoid membranes (TMs) for light-driven energy conversion. Recent studies on TM homeostasis (thylakostasis) have highlighted the essential role of the TM remodeling protein vesicle-inducing protein in plastid 1 (VIPP1). As a member of the endosomal sorting complexes required for transport-III (ESCRT-III)/phage shock protein A (PspA)/VIPP1 superfamily, VIPP1 forms large ring- and filament-like homo-oligomeric structures that exhibit a membrane remodeling activity. The oligomerization status was proposed to be modulated by the intrinsically disordered C-terminal tail (Vc), whereas its functional role remained unclear. Notably, this Vc region is conserved not only in photosynthetic VIPP1 but also in the PspA proteins of extremophilic species, implicating its role in membrane stress responses. To investigate the role of the Vc region in VIPP1 assembly, we performed coimmunoprecipitation assays in Arabidopsis chloroplasts and identified chloroplast-localized HSP70 proteins (cpHsc70) as major interactors. Among the two isoforms, cpHsc70-1 was found to be specifically required for modulating VIPP1 oligomeric assembly and dynamics in response to heat stress. Genetic analyses revealed that cpHsc70-1 facilitates the disassembly of VIPP1 oligomers, similarly to Vps4 ATPase in ESCRT-III; loss of either the Vc region or cpHsc70-1-impaired VIPP1 disassembly, resulting in more static oligomeric structures. Furthermore, cpHsc70-1 exhibited a broader role in chloroplast proteostasis, as the cphsc70-1 mutant showed impaired accumulation of green fluorescent protein (GFP)-fusion proteins. Together, our findings uncover a crucial crosstalk between proteostasis and thylakostasis in chloroplasts, coordinated by cpHsc70-1 and VIPP1 in response to membrane stress. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 28 9 2025 Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments 113274 EN Naotaka Aburatani Atmosphere and Ocean Research Institute, The University of Tokyo Wataru Takagi Atmosphere and Ocean Research Institute, The University of Tokyo Marty Kwok-Shing Wong Atmosphere and Ocean Research Institute, The University of Tokyo Nobuhiro Ogawa Atmosphere and Ocean Research Institute, The University of Tokyo Shigehiro Kuraku Department of Genomics and Evolutionary Biology, National Institute of Genetics Mana Sato Department of Genomics and Evolutionary Biology, National Institute of Genetics Kazuhiro Saito Ushimado Marine Institute, Faculty of Science, Okayama University Waichiro Godo Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Susumu Hyodo Atmosphere and Ocean Research Institute, The University of Tokyo Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold―the greatest change observed in vertebrates―partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 30 7 2025 How to report and discuss subgroup analyses in clinical practice guidelines? Evaluation procedure of the clinical and statistical relevancy 1259 1267 EN Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Satoru Miura Department of Internal Medicine, Niigata Cancer Center Hospital Yuko Oya Department of Respiratory Medicine and Allergy, Fujita Health University Tomohiro Sakamoto Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University Kentaro Tanaka Graduate School of Medical Sciences, Research Institute for Diseases of the Chest, Kyushu University Shunsuke Teraoka Internal Medicine III, Wakayama Medical University Masahiro Morise Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University The results of subgroup analyses of clinical trials are important reference information when considering the generalizability of a study treatment, i.e., providing the best treatment for each individual patient. The results of subgroup analyses are often presented in publications, etc. as forest plots focusing on patient backgrounds. However, it is important to fully understand and grasp some of the issues involved in subgroup analyses and to interpret the results carefully to apply them in clinical practice. Although the literature includes some reports on how subgroup analyses should be evaluated and handled for the purpose of establishing medical practice guidelines, most of the papers have mainly evaluated the reliability of subgroup analyses from a statistical perspective; few of them have incorporated clinical importance in their evaluations. Therefore, in December 2019, we established a Subgroup Analysis Review Committee consisting of oncologists specializing in lung cancer treatment and statistical experts among the members of the Guidelines Review Committee of the Japanese Lung Cancer Association, with the aim of appropriately reflecting subgroup analysis in Japanese lung cancer practice guidelines. We developed a new evaluation strategy to incorporate clinical aspects as well as reliability assessment. Specifically, on the basis of a clinical and statistical review of the problems with subgroup analyses presented as clinical trial results, we developed criteria and procedures to ensure consistency and fairness in the citation of clinical guidelines. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib 69 74 EN Shinya Wakatsuki Department of Obstetrics and Gynecology, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Akiko Ueno Department of Obstetrics and Gynecology, Kochi Health Sciences Center Takaomi Namba Department of Obstetrics and Gynecology, Kochi Health Sciences Center Yorito Yamamoto Department of Obstetrics and Gynecology, 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 Case Report 10.18926/AMO/70075 Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 5 2026 島根県猪目洞窟遺跡出土人骨の年代・食性・遺伝的特徴 20 39 EN Hideaki KANZAWA-KIRIYAMA Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Mai TAKIGAMI Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Tsuneo KAKUDA Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Leo SPEIDEL Center for Interdisciplinary Theoretical and Mathematical Sciences, RIKEN Garrett HELLENTHAL Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London Nancy BIRD Department of Genetics, Evolution and Environment, University College London Genetics Institute (UGI), University College London Yousuke KAWAI Genome Medical Science Project, National Institute of Global Health and Medicine, National Institute for Health Security NCBN Controls WGS Consortium Minoru SAKAMOTO National Museum of Japanese History Yuichi KAMEDA Division of Human Evolution, Paleontology and Anthropology, National Museum of Nature and Science, Tsukuba City, Ibaraki Prefecture Noboru ADACHI Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi Ken-ichi SHINODA National Museum of Nature and Science Naruya SAITOU National Institute of Genetics Tatsuhiko HAMADA Research Institute for the Dynamics of Civilizations, Okayama University 論文 (Research article) 10.18926/70052 This paper reports on the integrative research findings of the human bones excavated from the Inome Cave Site in Shimane Prefecture, based on dietary estimation using carbon and nitrogen isotope analysis, radiocarbon dating, and whole genome analysis. The dates of the analyzed human bones span a wide range, from the Middle to Late Kofun period, the Nara period to the Early Heian period, and the Middle to Late Heian period, indicating that the Inome Cave Site was continuously used as a burial place. Dietary habits were a mixture of C3 resources (C3 plants and terrestrial animals that consumed C3 plants) and marine resources, with individual variations in the intake of marine and terrestrial resources. A correlation was observed between differences in dietary habits and individual variations in the Jomon ratio in the nuclear genome, with individuals who consumed higher amounts of marine resources tending to have a higher Jomon ratio. This suggests that individuals with different backgrounds were buried in the same site due to interactions with surrounding settlements. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 5 1 2026 Cardiogenic cerebral infarction after Takotsubo cardiomyopathy in a patient with catatonia: A case report e70285 EN Masaki Fujiwara Department of Neuropsychiatry, Medical Development Field, Okayama University Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Kodama Okayama Psychiatric Medical Center Background: Takotsubo cardiomyopathy (TTC) is a transient cardiac condition often triggered by an emotional or physical stress. TTC usually has a benign clinical course with full recovery. However, in rare cases, TTC is complicated by cardiogenic shock, left ventricular rupture, or ventricular thrombus. We report a case of a patient with catatonia who developed TTC and subsequently experienced extensive cerebral infarction.<br> Case Presentation: A 71-year-old woman with no prior psychiatric history was admitted for catatonia following a suicide attempt. During hospitalization, she exhibited electrocardiography (ECG) abnormalities and elevated D-dimer levels. Transthoracic echocardiography revealed apical hypokinesis and basal hyperkinesis, consistent with TTC, along with an intraventricular thrombus. Cardiovascular CT angiography confirmed normal coronary arteries. She was diagnosed with TTC complicated by left ventricular thrombus and deep vein thrombosis. Anticoagulant therapy was initiated. Despite improvement in catatonia with lorazepam, she developed right hemiplegia and aphasia on Day 5 due to cardiogenic cerebral infarction from thromboembolism. Thrombolytic therapy was not indicated, and conservative treatment was provided. Although cardiac function normalized by Day 16, she was left with severe neurological deficits.<br> Conclusion: The case highlights the diagnostic challenges of TTC in non-communicative psychiatric patients and the potential for severe complications. Psychiatrists need to be aware of the development of TTC as a serious physical complication in patients with catatonia. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-3492 2026 A retrospective cohort study comparing periodontal regeneration using fibroblast growth factor‐2 versus autologous bone graft EN Toshiki Matsumoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin Nakamura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Ito‐Shinoda Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mai Sakamoto Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuki Nonomura Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetaka Ideguchi Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Okubo Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazu Takeuchi‐Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Shogo Takashiba Department of Pathophysiology–Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Fibroblast growth factor-2 (FGF-2) is a novel agent utilized in periodontal regeneration therapy. However, its clinical efficacy compared with autologous bone graft (ABG), a long-established treatment, remains unclear. This study aimed to compare the clinical outcomes of FGF-2 and ABG and to assess the impact of patient background factors on outcomes when using FGF-2.<br> Methods: We collected the subjects from January 2013 to September 2023. Clinical outcomes included the vertical bone defect improvement rate (VBDIR) and the probing pocket depth improvement (PPDI). Clinical outcomes between the two groups were compared using analysis of covariance (ANCOVA), adjusting for age, sex, smoking history, and hypertension. Additionally, a multilevel linear analysis was performed to assess factors influencing outcomes in FGF-2.<br> Results: A total of 180 sites from 141 patients (FGF-2: 150 sites; ABG: 30 sites) were evaluated. Both VBDIR and PPDI significantly improved postoperatively in both groups. There were no significant differences in clinical outcomes between FGF-2 and ABG. In FGF-2, smoking history was positively associated, while the preoperative bone defect angle (BDA) was negatively associated with clinical outcomes.<br> Conclusions: FGF-2 might exhibit clinical outcomes comparable to those of ABG, suggesting it is a clinically viable alternative for vertical bone defects. When using FGF-2, patient-specific factors such as smoking history and preoperative BDA should be considered carefully.<br> The name in the trial registry: A survey of clinical practice and evaluation of treatment outcomes of periodontal regenerative therapy using REGROTH at Okayama University Hospital No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 11 44 2025 Structural insights into the divergent evolution of a photosystem I supercomplex in Euglena gracilis eaea6241 EN Koji Kato Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yoshiki Nakajima Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Runa Sakamoto Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Minoru Kumazawa Institute of Low Temperature Science, Hokkaido University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Takahiro Ishikawa Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University Jian-Ren Shen Research Institute for Interdisciplinary Science, Advanced Research Field, and Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsushi Takabayashi Institute of Low Temperature Science, Hokkaido University Ryo Nagao Faculty of Agriculture, Shizuoka University Photosystem I (PSI) forms supercomplexes with light-harvesting complexes (LHCs) to perform oxygenic photosynthesis. Here, we report a 2.82-angstrom cryo–electron microscopy structure of the PSI-LHCI supercomplex from Euglena gracilis, a eukaryotic alga with secondary green alga-derived plastids. The structure reveals a PSI monomer core with eight subunits and 13 asymmetrically arranged LHCI proteins. Euglena LHCIs bind diadinoxanthin, which is one of the carotenoids typically associated with red-lineage LHCs and is not present in the canonical LHCI belt found in green-lineage PSI-LHCI structures. Phylogenetic analysis shows that the Euglena LHCIs originated from LHCII-related clades rather than from the green-lineage LHCI group and that the nuclear-encoded PSI subunit PsaD likely originated from cyanobacteria via horizontal gene transfer. These observations indicate a mosaic origin of the Euglena PSI-LHCI. Our findings uncover a noncanonical light-harvesting architecture and highlight the structural and evolutionary plasticity of photosynthetic systems, illustrating how endosymbiotic acquisition and lineage-specific adaptation shape divergent light-harvesting strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 1 2025 Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING 10 EN Masaki Sakamoto 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 Tetsuya Katayama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yu Mikane Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunya Hanzawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Hashimoto 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 Yoshihiko Kakiuchi 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 Kunitoshi Shigeyasu 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 Kagawa Department of Gastroenterological Surgery, 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 The gut microbiota plays an essential role in regulating host immunity, and its metabolites such as butyrate exert immunomodulatory effects by acting as histone deacetylase inhibitors. Oncolytic virotherapy has emerged as a promising approach for cancer treatment, and we have developed OBP-702, a telomerase-specific oncolytic adenovirus that expresses p53 and elicits strong systemic antitumor responses. In this study, the potential synergy between butyrate and OBP-702 was investigated in colorectal cancer models. Using human and murine colorectal carcinoma cell lines, butyrate was found to directly enhance the infectivity of OBP-702 by upregulating CAR and integrins, thereby promoting apoptosis and autophagy in tumor cells. In addition, butyrate indirectly boosted systemic antitumor immunity by upregulating MHC-I expression through activation of the cGAS-STING pathway and enhancing CD8 + T cell recruitment via CXCL10 secretion. These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2025 Genomic Profiling of Pediatric Solid Tumors With a Dual DNA/RNA Panel: JCCG-TOP2 Study EN Kayoko Tao Department of Pediatrics, National Cancer Center Hospital Takako Yoshioka Department of Pathology, National Center for Child Health and Development Miho Kato Department of Childhood Cancer Data Management, National Center for Child Health and Development Kazuyuki Komatsu Department of Pediatrics, Hamamatsu University School of Medicine Shinichi Tsujimoto Department of Pediatrics, Yokohama City University Kenichi Sakamoto Department of Pediatrics, Shinshu University School of Medicine Kazuki Tanimura Department of Pediatrics, National Cancer Center Hospital Minako Sugiyama Department of Pediatrics, National Cancer Center Hospital Masahiro Sekiguchi Department of Pediatrics, The University of Tokyo Yoshiko Nakano Department of Pediatrics, The University of Tokyo Yoshihiro Otani Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushi Yatabe Department of Diagnostic Pathology, National Cancer Center Hospital Akihiko Yoshida Department of Diagnostic Pathology, National Cancer Center Hospital Hajime Okita Department of Pathology, Keio University School of Medicine Junko Hirato Department of Pathology, Public Tomioka General Hospital Kenichi Kohashi Department of Pathology, Graduate School of Medicine, Osaka Metropolitan University Yukichi Tanaka Department of Pathology, Kanagawa Children's Medical Center Shinji Kohsaka Division of Cellular Signaling, National Cancer Center Research Institute Takashi Kubo Department of Clinical Genomics, National Cancer Center Research Institute Kuniko Sunami Department of Laboratory Medicine, National Cancer Center Hospital Makoto Hirata Department of Genetic Medicine and Services, National Cancer Center Hospital Shuichi Tsutsumi Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Hiroyuki Aburatani Genome Science & Medicine Division, Research Center of Advanced Science and Technology, The University of Tokyo Katsuyoshi Koh Department of Hematology and Oncology, Saitama Children's Medical Center Masahiro Hirayama Department of Pediatrics, Mie University Graduate School of Medicine Shuhei Karakawa Department of Pediatrics, Hiroshima University Hospital Yukayo Terashita Department of Pediatrics, Hokkaido University Hospital Hiroyuki Fujisaki Department of Pediatric Hematology and Oncology, Osaka City General Hospital Takeshi Yagi Okinawa Prefectural Nanbu Medical Center & Children's Medical Center Akihiro Yoneda Department of Pediatric Surgery, National Center for Child Health and Development Shinji Mochizuki Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Hiroyuki Shichino Department of Pediatrics, National Center for Global Health and Medicine, Japan Institute for Health Security Tatsuya Suzuki Department of Hematology, National Cancer Center Hospital Tetsuya Takimoto Department of Childhood Cancer Data Management, National Center for Child Health and Development Koichi Ichimura Department of Pathology, Kyorin University Faculty of Medicine Chitose Ogawa Department of Pediatrics, National Cancer Center Hospital Kimikazu Matsumoto Children's Cancer Center National Center for Child Health and Development Hitoshi Ichikawa Department of Clinical Genomics, National Cancer Center Research Institute Motohiro Kato Department of Pediatrics, The University of Tokyo To develop an optimized genomic medicine platform for pediatric cancers, a nationwide cancer genome profiling project was conducted from January 2022 to February 2023 in collaboration with the Japan Children's Cancer Group. This prospective observational study analyzed matched blood and FFPE tumor samples from patients aged 0–29 years with solid tumors. Genomic analysis used the TOP2 hybrid capture–enrichment system, targeting 737 and 455 genes in the DNA and RNA panels, along with allele-specific genome copy number alterations. A total of 210 patients from 50 institutions were enrolled across Japan (median age, 8 years; range, 0–25). Of these, 154 (77%) were enrolled at diagnosis or during/after initial treatment and 56 (27%) at disease progression or relapse. The TOP2 findings had great benefits in clarifying the diagnosis of pediatric solid tumors. Among the 204 patients with genomic results, 147 (72%) had potentially actionable findings, including diagnostic, prognostic, and therapeutic findings in 111 (54%), 61 (30%), and 64 (31%), respectively. Oncogenic fusions were noted in 45 (23%) patients. A copy number alteration was identified in at least one genomic region in 170 (83%) patients. Two patients exhibited a high tumor mutation burden. Seventeen (8%) patients harbored a germline pathogenic/likely pathogenic variant in cancer-predisposing genes. This study highlighted the feasibility of implementing a nationwide precision medicine platform and the clinical utility of the TOP2 system for pediatric cancers. The results support the integration of genomic data into the standard clinical care of pediatric patients with cancer, both at diagnosis and at relapse. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Ileus Tube-Related Intussusception: A Case Report and Review of 80 Previously Reported Cases 469 474 EN Teruyuki Tsujii Department of Surgery, Matsuda Hospital Tatsuo Matsuda Department of Surgery, Matsuda Hospital Yuji Kimura Department of Surgery, Matsuda Hospital Ryoichi Katsube Department of Surgery, Matsuda Hospital Hironori Iwadou Department of Surgery, Matsuda Hospital Sadami Funabiki Department of Surgery, Matsuda Hospital Yasuaki Kamikawa Department of Surgery, Matsuda Hospital Tadakazu Matsuda Department of Surgery, Matsuda Hospital Case Report 10.18926/AMO/69851 We report a rare case of ileus tube-related intussusception in an adult. A 56-year-old man with adhesive bowel obstruction was treated with a nasointestinal ileus tube. Although his condition initially improved, persistent abdominal pain led to the diagnosis of intussusception via CT imaging. Manual repositioning of the tube resolved the intussusception without the need for bowel resection. A review of 80 previously reported cases of ileus tube-associated intussusception (total 81 cases, 95 lesions) highlighted the timing of onset, treatment strategies, and precautions. Early detection and diagnosis are crucial to prevent severe complications and preserve bowel function. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older 405 412 EN Chihiro Ouchi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuro Morita 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 Original Article 10.18926/AMO/69842 We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1340-2838 32 6 2025 MedakaBase as a unified genomic resource platform for medaka fish biology dsaf030 EN Kenji Morikami Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Yasuhiro Tanizawa Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Masaru Yagura Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Mika Sakamoto Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Shoko Kawamoto Department of Genetics, Sokendai (Graduate University for Advanced Studies) Yasukazu Nakamura Genome Informatics Laboratory, National Institute of Genetics, Research Organization of Information and Systems Katsushi Yamaguchi Trans-Omics Facility, National Institute for Basic Biology Shuji Shigenobu Trans-Omics Facility, National Institute for Basic Biology Kiyoshi Naruse Laboratory of Bioresources, National Institute for Basic Biology, National Institutes of Natural Sciences Satoshi Ansai Ushimado Marine Institute, Okayama University Shigehiro Kuraku Molecular Life History Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Research Organization of Information and Systems Medaka, a group of small, mostly freshwater fishes in the teleost order Beloniformes, includes the rice fish Oryzias latipes, a useful model organism studied in diverse biological fields. Chromosome-scale genome sequences of the Hd-rR strain of this species were obtained in 2007, and its improved version has facilitated various genome-wide studies. However, despite its widespread utility, omics data for O. latipes are dispersed across various public databases and lack a unified platform. To address this, the medaka section of the National Bioresource Project (NBRP) of Japan established a genome informatics team in 2022 tasked with providing various in silico solutions for bench biologists. This initiative led to the launch of MedakaBase (https://medakabase.nbrp.jp), a web server that enables gene-oriented analysis including exhaustive sequence similarity searches. MedakaBase also provides on-demand browsing of diverse genome-wide datasets, including tissue-specific transcriptomes and intraspecific genomic variations, integrated with gene models from different sources. Additionally, the platform offers gene models optimized for single-cell transcriptome analysis, which often requires coverage of the 3′ untranslated region (UTR) of transcripts. Currently, MedakaBase provides genome-wide data for seven Oryzias species, including original data for O. mekongensis and O. luzonensis produced by the NBRP team. This article outlines technical details behind the data provided by MedakaBase. 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<br> 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.<br> Methods<br> 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.<br> Results<br> 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).<br> Conclusion<br> 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.

Springer Science and Business Media LLC Acta Medica Okayama 0944-1174 60 12 2025 Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B) 1584 1595 EN Satoshi Kobayashi Department of Gastroenterology, Kanagawa Cancer Center Kohei Nakachi Department of Medical Oncology, Tochigi Cancer Center Kouji Yamamoto Department of Biostatistics, Yokohama City University School of Medicine Makoto Ueno Department of Gastroenterology, Kanagawa Cancer Center Yuta Maruki Kenji Ikezawa Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute Takeshi Terashima Department of Gastroenterology, Kanazawa University Hospital Satoshi Shimizu Department of Gastroenterology, Kanazawa University Hospital Kotoe Oshima Division of Gastrointestinal Oncology, Shizuoka Cancer Center Kunihiro Tsuji Department of Gastroenterology, Ishikawa Prefectural Central Hospital Yoshiharu Masaki Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine Hidetaka Tsumura Department of Gastroenterological Oncology, Hyogo Cancer Center Taro Shibuki Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East Masato Ozaka Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research Naohiro Okano Department of Medical Oncology, Kyorin University Faculty of Medicine Yukiyasu Okamura Division of Digestive Surgery, Department of Surgery, Nihon University School of Medicine Kumiko Umemoto Department of Clinical Oncology, St. Marianna University School of Medicine Tatsunori Satoh Department of Gastroenterology, Shizuoka General Hospital Yasushi Kojima Department of Gastroenterology, National Center for Global Health and Medicine Kazuhiko Shioji Department of Gastroenterology, Niigata Cancer Center Hospital Hiroko Nebiki Department of Gastroenterology, Osaka City General Hospital Toshifumi Doi Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Atsushi Naganuma Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center Shigeki Kataoka Department of Clinical Oncology, Graduate School of Medicine Faculty of Medicine, Kyoto University Emiri Kita Department of Gastroenterology, Chiba Cancer Center Hiroyuki Asama Department of Gastroenterology, Fukushima Medical University Kaoru Tsuchiya Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital Michiaki Unno Department of Surgery, Tohoku University Graduate School of Medicine Reiko Ashida Second Department of Internal Medicine, Wakayama Medical University Kazuyuki Matsumoto Department of Gastroenterology, Okayama University Graduate School of Medicine Izumi Ohno Department of Gastroenterology, Chiba University Graduate School of Medicine Takao Itoi Department of Gastroenterology, Tokyo Medical University Yuji Negoro Department of Oncologial Medicine, Kochi Health Sciences Center Yasunari Sakamoto Department of Gastroenterology and Hepatology, International University of Health and Welfare Atami Hospital Shiho Arima Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences Akinori Asagi Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center Hiroyuki Okuyama Department of Medical Oncology, Kagawa University Hospital Yoshito Komatsu Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center Noritoshi Kobayashi Department of Oncology, School of Medicine Graduate School of Medicine, Yokohama City University Hiroaki Nagano Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine Junji Furuse Department of Gastroenterology, Kanagawa Cancer Center Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.<br> Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.<br> Results: This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).<br> Conclusions: GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 10 2025 Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancer e95808 EN Yoshihiro Sakamoto Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Hamada Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimi Katayama Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Sugihara Department of Orthopedic Surgery, Shikoku Cancer Center Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Skeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2025 Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice EN NGUYEN DUY HOANG Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2025 Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer EN Kohji Tanakaya Department of Surgery, National Hospital Organization Iwakuni Clinical Center Tatsuro Yamaguchi Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Keiji Hirata Department of Surgery 1, University of Occupational and Environmental Health Masayoshi Yamada Endoscopy Division, National Cancer Center Hospital Kensuke Kumamoto Department of Genome Medical Science and Medical Genetics, Faculty of Medicine, Kagawa University Yasuki Akiyama Department of Surgery 1, University of Occupational and Environmental Health Kei Ishimaru Division of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University Koichi Okamoto Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science Yuko Kawasaki College of Nursing, University of Hyogo Keigo Komine Department of Medical Oncology, Tohoku University Hospital Akira Sakamoto Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Shibata Himawari-No-Kai (Sunflower Association), a Patient Advocacy Group for Individuals and Families Affected By Lynch Syndrome Yusaku Shimamoto Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine Hideki Shimodaira Division of Medical Oncology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Shigeki Sekine Department of Pathology, Keio University School of Medicine Akinari Takao Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Misato Takao Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Yasuyuki Takamizawa Department of Colorectal Surgery, National Cancer Center Hospital Yoji Takeuchi Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine Noriko Tanabe Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University Fumitaka Taniguchi Department of Surgery, Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital Akiko Chino Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Hourin Cho Endoscopy Center, Tokyo Medical University Hospital Satoru Doi Harmony Line (Association for Patients and Families With Familial Adenomatous Polyposis) Takeshi Nakajima Division of Hereditary Tumors, Department of Genetic Oncology, Osaka International Cancer Institute Sakiko Nakamori Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Yoshiko Nakayama Department of Pediatrics, Shinshu University School of Medicine Toshiya Nagasaki Department of Gastroenterological Surgery, Saitama Cancer Center Hisashi Hasumi Department of Urology, Yokohama City University Kouji Banno Center of Maternal -Fetal/Neonatal Medicine, Hiroshima University Hospital Takao Hinoi Department of Clinical and Molecular Genetics, Hiroshima University Hospital Kenji Fujiyoshi Department of Surgery, Kurume University School of Medicine Takahiro Horimatsu Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital Kenta Masuda Department of Obstetrics and Gynecology, Keio University School of Medicine Masashi Miguchi Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital Yusuke Mizuuchi Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University Yasuyuki Miyakura Department of Colon and Pelvic Surgery, Cancer Prevention and Genetic Counseling, Tochigi Cancer Center Michihiro Mutoh Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Takahiro Yoshioka Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinji Tanaka JA Onomichi General Hospital Kazuhiro Sakamoto Koshigaya Municipal Hospital Kentaro Sakamaki Faculty of Health Data Science, Juntendo University Michio Itabashi Saiseikai Kazo Hospital Hideyuki Ishida Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University Naohiro Tomita Division of Cancer Treatment , Toyonaka Municipal Hospital Kenichi Sugihara Institute of Science Tokyo Yoichi Ajioka Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4729 2025 Evaluation of the small-field output factor in eclipse modeling methods using representative beam and measured data with averaged ionization chamber and diode detector measurements EN Kunio Nishioka Department of Radiology, Tokuyama Central Hospital Yuki Kunii Department of Radiology, Tokuyama Central Hospital Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Yuichi Sakamoto Department of Radiology, Tokuyama Central Hospital Akira Nakamoto Department of Radiology, Tokuyama Central Hospital Shotaro Takahashi Department of Radiology, Tokuyama Central Hospital Beam modeling for radiotherapy treatment planning systems (RTPS) can be performed using representative beam data (RBD) or direct measurements. However, RBD typically excludes output factor (OPF) measurements for fields smaller than 3 × 3 cm2. The Eclipse treatment planning system addresses this limitation by incorporating measured OPF data for fields as small as 1 × 1 cm2. Although existing studies have primarily examined the accuracy of small-field OPFs for plastic scintillator detectors, studies directly comparing the OPF values obtained through RBD modeling with and without OPF measurements for small field sizes are limited. Therefore, this study proposes a novel measurement approach using data averaged from an ion chamber and diode detector for small-field dosimetry to provide critical insights into the integration of OPFs for these small field sizes in RBD-based beam modeling. We systematically evaluated the impact of small-field OPF measurements on beam modeling accuracy by comparing three distinct approaches: (1) RBD-based modeling without small-field OPF data, (2) RBD-based modeling incorporating measured small-field OPF data, and (3) modeling based solely on measured data, with and without the inclusion of 1 × 1 cm2 field sizes. In addition, we compared OPF values obtained from a W2 plastic scintillator detector with the averaged OPF values from a PinPoint 3D ion chamber and EDGE diode detector across multiple beam energies and flattening filter-free (FFF) configurations. Our analysis included field sizes ranging from 1 × 1 cm2 to 40 × 40 cm2. The results demonstrated that for square fields, OPF calculation differences between RBD modeling with and without measured data were < 1.5%, < 4.5%, and < 4.5% at 1 × 1 cm2, and < 0.5%, < 1.5%, and < 1.5% at 2  ×  2 cm2, respectively. The RBD group exhibited a trend in which the OPF difference increased with the expansion of the irradiation field size. Notably, the most significant variations between modeling approaches occurred along the upper jaw expansion direction in rectangular fields. This suggests that a thorough evaluation is necessary for modeling results with an OPF ≤  1 × 1 cm2. This study highlights the advantages and disadvantages of beam modeling using measured OPF and RBD, providing valuable insights for future facilities that rely solely on RBD for beam modeling. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0276-3478 2025 DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model EN Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Wada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Miyazaki Sumitomo Pharma Co. Ltd Taro Kato Sumitomo Pharma Co. Ltd Yoshihiro Horiuchi Sumitomo Pharma Co. Ltd Hiroshi Kirii Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology Hoang Duy Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Yoshio Ohya Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Asada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Miyazaki Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on the pathophysiology of AN.<br> Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11β-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.<br> Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.<br> Conclusion: Inhibition of 11β-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1791-2997 33 1 2025 Protective impact of landiolol against acute lung injury following hemorrhagic shock and resuscitation in rats 22 EN Risa Sakamoto Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University Medical School Yifu Lu Department of Human Anatomy, Shantou University Medical College Yaqiang Li 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 Department of Anesthesiology, Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation, leading to acute lung injury (ALI). Notably, blocking β1 receptors can lead to organ protection through anti‑inflammatory and anti‑apoptotic effects. Additionally, although the β1 receptor pathway is blocked by the β1 blocker, the β2 receptor pathway may be preserved and activate the 5' adenosine monophosphate‑activated protein kinase (AMPK) pathway. The present study aimed to examine whether administration of the β1 blocker landiolol could achieve lung protection in a model of HSR‑ALI, alongside improvements in inflammation and apoptosis. Male Sprague‑Dawley rats underwent hemorrhage keeping their mean arterial pressure at 30 mmHg for 1 h. Resuscitation by reinfusion was initiated to restore blood pressure to pre‑hemorrhage levels for >15 min, followed by a 45‑min stabilization period to create the HSR‑ALI model. Landiolol (100 mg/kg/min) or saline was continuously administered after resuscitation. The lung tissues, which were collected for assessing inflammation and apoptosis‑related damage, underwent analyses, including histological examination, neutrophil count, assessment of lung wet/dry weight ratio, detection of the mRNA levels of tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS), identification of terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL)‑positive cells, and evaluation of caspase‑3 expression. In addition, phosphorylated AMPKα (pAMPKα) expression was tested via western blotting. Compared with the HSR/saline group, the HSR/landiolol group demonstrated a reduction in lung tissue damage score, and significant reductions in neutrophil count, lung wet/dry weight ratio, lung TNF‑α and iNOS mRNA levels, TUNEL‑positive cells and cleaved caspase‑3 expression. Furthermore, landiolol administration following HSR treatment increased pAMPKα expression. No significant hypotension occurred between the HSR/landiolol and HSR/saline groups; and blood loss did not differ significantly between the groups. In conclusion, landiolol administration after HSR reduced lung inflammation and apoptosis, suggesting a potential improvement in tissue damage. Furthermore, pAMPKα activation in the HSR/landiolol group may be the mechanism underlying the pulmonary protective effects of landiolol. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy 38590 EN Chiaki Yagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Kadowaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Yoshida Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masaki Sakamoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Hamada Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoma Sugimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Ohtani Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kumon Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. No potential conflict of interest relevant to this article was reported.

Copernicus GmbH Acta Medica Okayama 2194-9034 XLVIII-4/W9-2024 2024 3D MONITORING OF COASTAL EROSION CONTROL STRUCTURES USING UAV 313 320 EN N. Sakamoto Graduate School of Environmental and Life Science, Okayama University S. Nishiyama Graduate School of Environmental and Life Science, Okayama University Coastal erosion has increasingly become a problem in recent years due to rising sea levels caused by global warming. To prevent further coastal erosion and damage, control structures like seawalls and breakwaters have been installed along vulnerable coastlines. However, it is crucial that these structures are regularly and thoroughly inspected for any abnormalities or deformations. At present, inspections are done manually by visual surveys which are time-consuming and inefficient. There is great potential to optimize this process using drone technology equipped with 3D laser scanners. In this study, we utilized a drone with a green laser scanner to inspect and diagnose control structures along the coast. We conducted surveys to determine the basic performance of this approach and used ICP algorithms to extract any deformations in vanishing wave blocks over two time periods. Our results showed high variability in basic performance due to the influence of waves during the surveys. However, we were still able to detect strain of around 50 cm in a submerged breakwater located 3 meters below the water's surface. Furthermore, an overall settlement of approximately 34 cm was observed in the vanishing wave blocks along with some localized movements. This demonstrates that drones can be successfully implemented for efficient inspection, diagnosis and detection of abnormalities and deformations in coastal structures that are extremely difficult to identify through visual surveys alone. The use of this advanced technology will allow for quicker identification of at-risk structures, enabling timely maintenance and prevention of further coastal erosion. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-4928 50 2026 Effects of grain size and crystal orientation on tensile properties of pure titanium thin wires 114240 EN Junji Sakamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoya Tada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Uemori Faculty of Environmental, Life, Natural Science and Technology, Okayama University To clarify the effects of the grain size and crystal orientation on the tensile properties of pure titanium thin wires, tensile and stepwise tensile tests were conducted on pure titanium wires with diameters of approximately 180 μm and different average grain sizes (52, 37, 23, and 3.8 μm). When the grain size was large, the fracture strain was significantly smaller, the variation in tensile strength was larger, and the grain size threshold for such properties was a grain-size ratio to wire diameter of 0.13 or greater. For larger grain sizes, the slip system with the highest modified Schmid factor (MSF), which is the Schmid factor divided by the critical resolved shear stress of each slip system, was activated in all 15 grains whereas for smaller grain sizes, the percentage of slip systems activated with the highest MSF was slightly lower. In addition, the fracture location in a thin wire with larger grain sizes was highly correlated with the average MSF of the grains in the cross-section. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1752-8054 18 10 2025 Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study e70318 EN Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Takehiro Kawashiri Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Keisuke Mine Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Soichiro Ushio Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Noriko Hida Department of Clinical Research and Development, Graduate School of Pharmacy, SHOWA Medical University Kenji Momo Department of Hospital Pharmaceutics, Graduate School of Pharmacy, SHOWA Medical University Masanobu Uchiyama Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University Mami Uchida Department of Pharmacy, Fukuoka University Hospital Mamoru Tanaka Division of Pharmacy, Ehime University Hospital Noriaki Hidaka Division of Pharmacy, Ehime University Hospital Hideki Yasui Center for Clinical Research, Hamamatsu University Hospital Masahiro Ueda Faculty of Pharmaceutical Sciences, Setsunan University Ryohei Fujii Department of Pharmacy, Kansai Medical University Hospital Misaki Hashimoto Department of Pharmacy, Kansai Medical University Hospital Yasutaka Sakamoto Department of Pharmacy, Yokohama City University Hospital Kana Uyama Department of Pharmacy, Yokohama City University Hospital Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Yuki Hanai Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University Ayaka Tsuboya Department of Pharmacy, Kawasaki Municipal Tama Hospital Keisuke Suzuki Innovation Center for Translational Research, National Center for Geriatrics and Gerontology Naoya Kamiyama Asahikawa Medical University Hospital Hiromi Hagiwara Nagoya City University Hospital Naoto Okada Pharmacy Department, Yamaguchi University Hospital Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, University of Tokushima Graduate School of Biomedical Sciences Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Periodontitis associated with Porphyromonas gingivalis infection is a risk factor for infertility through uterine hypertrophy 34964 EN Chiaki Kamei-Nagata Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidefumi Sako Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kyosuke Sakaida Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Masa-aki Nakayama Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Moyuka Kubota-Takamori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumiko Kiyama Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Ishii Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimito Hirai Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ikeda Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masako Tai-Tokuzen Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Ai Sakamoto Center for Reproductive Medicine, Miyake Clinic Machiko Kiyokawa Center for Reproductive Medicine, Miyake Clinic Tomomi Yamanishi Center for Reproductive Medicine, Miyake Clinic Takashi Oda Center for Reproductive Medicine, Miyake Clinic Masayuki Takigawa Miyake Hello Dental Clinic, Pediatric Dentistry and Orthodontics Tadashi Yamamoto The Center for Graduate Medical Education (Dental Division), Okayama University Hospital Takahito Miyake Center for Reproductive Medicine, Miyake Clinic Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Periodontitis has recently been recognized as a potential risk factor for infertility due to its adverse effect on conception, although the underlying mechanisms remain unclear. This study investigated serum IgG antibody titers against periodontopathogenic bacteria in women with unexplained infertility and investigated how periodontal inflammation affects pregnancy and uterine function using a ligature-induced periodontitis mouse model infected with Porphyromonas gingivalis (Pg). IgG antibody titers against seven periodontopathogenic bacteria strains were measured by ELISA in 76 spontaneously pregnant women and 70 women undergoing infertility treatment. In the in vivo study, periodontitis mice were bred four weeks after periodontitis induction. Birth numbers, newborn weights, and gestation periods were assessed. To evaluate periodontal inflammation, alveolar bone, serum, and uterus was collected before mating. Uterine tissue was evaluated through histological and immunohistochemical staining. Women receiving infertility treatment were significantly older and had higher IgG titers against three Pg strains. Periodontitis mice had fewer births, lower newborn weights, and increased uterine cross-sectional areas. Additionally, elevated estrogen receptor α and progesterone receptor expression levels were observed in endometrial and stromal tissues. These results suggest that periodontitis may cause uterine hypertrophy and hormone receptor changes, potentially impairing pregnancy. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2050-7488 13 35 2025 Thermally polymerizable phthalocyanine realizes a metal–nitrogen-doped carbon material featuring a defined single-atom catalyst motif with CO2RR activity 28887 28895 EN Yuki Sano Department of Chemistry, Graduate School of Science, Tohoku University Daichi Nakajima Department of Chemistry, Graduate School of Science, Tohoku University Biplab Manna Center for Basic Research on Materials, National Institute for Materials Science Koki Chida Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Ryojun Toyoda Department of Chemistry, Graduate School of Science, Tohoku University Shinya Takaishi Department of Chemistry, Graduate School of Science, Tohoku University Kazuyuki Iwase Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Koji Harano Center for Basic Research on Materials, National Institute for Materials Science Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Takeharu Yoshii Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Ryota Sakamoto Department of Chemistry, Graduate School of Science, Tohoku University Metal–nitrogen-doped carbon materials (MNCs) exhibit good electrocatalytic performance owing to the intrinsic advantages of carbon-based materials and the presence of isolated and stabilized metal atoms coordinated by nitrogen sites. However, conventional high-temperature pyrolysis of precursor molecules make it difficult to control the coordination structure precisely. To address this issue, here we report a new synthesis strategy for MNCs. Specifically, we design and synthesize Ni-phthalocyanine functionalized with ethynyl groups as solid-state thermal polymerization points. After depositing the Ni-phthalocyanine precursor on a carbon support and performing a thermal treatment, the resultant carbon composite material features a Ni–N4 coordination structure derived from the precursor, and enhanced porosity. This material demonstrates high catalytic activity for the CO2 reduction reaction (CO2RR). Our synthetic approach is applicable to various precursor molecules and carbon supports, paving the way for the further development of MNC-based electrode catalysts. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1743-6095 2025 Dual-action intranasal oxytocin enhances both male sexual performance and fertility in rats 1 3 EN Chica Enomoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takumi Oti Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takahiro Yamanaka Laboratory of Reproductive Endocrinology, Graduate School of Integrated Sciences for Life, Hiroshima University Masayuki Shimada Laboratory of Reproductive Endocrinology, Graduate School of Integrated Sciences for Life, Hiroshima University Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0889 198 1 2025 The thylakoid membrane remodeling protein VIPP1 forms bundled oligomers in tobacco chloroplasts kiaf137 EN Sarah W Gachie Institute of Plant Science and Resources, Okayama University Alexandre Muhire Institute of Plant Science and Resources, Okayama University Di Li Institute of Plant Science and Resources, Okayama University Akihiro Kawamoto Institute for Protein Research, Osaka University Noriko Takeda-Kamiya Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Yumi Goto Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Mayuko Sato Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Kiminori Toyooka Mass Spectrometry and Microscopy Unit, RIKEN Center for Sustainable Resource Science Ryo Yoshimura Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Lingang Zhang School of Life Sciences, Inner Mongolia University/Key Laboratory of Herbage and Endemic Crop Biotechnology Genji Kurisu Institute for Protein Research, Osaka University Toru Terachi Faculty of Life Sciences, Kyoto Sangyo University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University The thylakoid membrane (TM) serves as the scaffold for oxygen-evolving photosynthesis, hosting the protein complexes responsible for the light reactions and ATP synthesis. Vesicle inducing protein in plastid 1 (VIPP1), a key protein in TM remodeling, has been recognized as essential for TM homeostasis. In vitro studies of cyanobacterial VIPP1 demonstrated its ability to form large homo-oligomers (2 MDa) manifesting as ring-like or filament-like assemblies associated with membranes. Similarly, VIPP1 in Chlamydomonas reinhardtii assembles into rods that encapsulate liposomes or into stacked spiral structures. However, the nature of VIPP1 assemblies in chloroplasts, particularly in Arabidopsis, remains uncharacterized. Here, we expressed Arabidopsis thaliana VIPP1 fused to GFP (AtVIPP1-GFP) in tobacco (Nicotiana tabacum) chloroplasts and performed transmission electron microscopy (TEM). A purified AtVIPP1-GFP fraction was enriched with long filamentous tubule-like structures. Detailed TEM observations of chloroplasts in fixed resin-embedded tissues identified VIPP1 assemblies in situ that appeared to colocalize with GFP fluorescence. Electron tomography demonstrated that the AtVIPP1 oligomers consisted of bundled filaments near membranes, some of which appeared connected to the TM or inner chloroplast envelope at their contact sites. The observed bundles were never detected in wild-type Arabidopsis but were observed in Arabidopsis vipp1 mutants expressing AtVIPP1-GFP. Taken together, we propose that the bundled filaments are the dominant AtVIPP1 oligomers that represent its static state in vivo. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 2025 Thylakostasis: key factors in thylakoid membrane organization with emphasis on biogenesis and remodeling proteins in vascular plants pcaf098 EN Wataru Sakamoto Institute of Plant Science and Resources, Okayama University The thylakoid membrane (TM), a defining feature for almost all oxygen-evolving photosynthetic organisms, serves as the structural foundation for light-driven energy conversion. In vascular plants, the TM evolved into a complex architecture composed of single-layered stroma thylakoids and stacked grana thylakoids, enabling the spatial organization of two photosystems (PSII and PSI) to optimize light capture and energy transfer. In addition, two membrane regions, one connecting these two compartments (grana margin) and the other corresponding to the curvature domain in grana, function in dissipating excess energy, balancing electron transfer, and maintaining functional PSII. Recent advances in electron microscopy imaging and proteome analysis of membrane subcompartments have provided new insights into the structure and dynamic adaptations of the TM in response to diverse environmental conditions. To describe the mechanisms that govern TM architecture, dynamics, and integrity, I am introducing the concept of “thylakostasis” (thylakoid homeostasis). Here, I provide an overview of the molecular components and processes central to thylakostasis, including the biosynthesis of lipids, chlorophyll, and proteins. I focus particularly on the membrane remodeling proteins whose functions have been elucidated recently, such as VIPP1, a member of the evolutionarily conserved PspA/ESCRT-III superfamily; FZL, a dynamin-like GTPase; and CURT1, a curvature-inducing protein unique to photosynthetic organisms. Together, these factors orchestrate TM biogenesis, remodeling, and adaptive flexibility that is essential for photosynthetic efficiency. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0753-3322 188 2025 Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study 118137 EN Yoshika Sakamoto Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Mitsuhiro Goda Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Nanami Tomochika Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Wakana Murakawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Fuka Aizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenta Yagi Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Yuki Izawa-Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Yoshito Zamami Department of Pharmacy, Okayama University Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Sunitinib (SUN), a drug used to treat advanced renal cell carcinoma and other cancers, causes cardiotoxicity. This study aimed to identify a potential drug candidate to counteract SUN-induced cardiotoxicity. We analysed real-world data from adverse event report databases of existing clinically approved drugs to identify potential candidates. Through in silico analyses and in vitro experiments, the mechanisms of action were determined. The study identified calcitriol (CTL), an active form of vitamin D, as a promising candidate against SUN-induced cardiotoxicity. In H9c2 cells, SUN decreased cell viability significantly, whereas CTL mitigated this effect significantly. The SUN-treated group exhibited increased autophagy in H9c2 cells, which was reduced significantly in the CTL group. Bioinformatics analysis using Ingenuity Pathway Analysis revealed the mechanistic target of rapamycin (mTOR) as a common factor between autophagy and CTL. Notably, rapamycin, an mTOR inhibitor, nullified the effects of CTL on cell viability and autophagy. Furthermore, SUN treatment led to significant reductions in cardiomyocyte diameters and increases in their widths, changes that were inhibited by CTL. SUN also induced morphological changes in surviving H9c2 cells, causing them to adopt a rounded shape, whereas CTL improved their morphology to resemble the elongated shape of the control group. In conclusion, the findings of the present study suggest that CTL has the potential to prevent SUN-induced cardiomyocyte damage through autophagy, particularly via mTOR-mediated pathways. The findings indicate that CTL could serve as an effective prophylactic agent against SUN-induced cardiotoxicity, offering a promising avenue for further research and potential clinical applications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 3 2025 Occupational therapist‐guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report e70167 EN Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Ohya Department of Neuropsychiatry, Okayama University Hospital Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Yuko Okahisa Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: Moderate exercise increases white blood cells and neutrophils. However, there are no reports on the relationship between exercise intensity and these cells. We observed a patient taking clozapine whose white blood cell and neutrophil counts were borderline. Supervised exercise therapy with an occupational therapist stabilized these counts.<Br> Case Presentation: A 50-year-old woman with treatment-resistant schizophrenia was prescribed clozapine. By Day 63, the clozapine dosage had been increased to 450 mg/day. Additionally, she was advised to perform a 30-min walking exercise program 1 h before blood tests. Exercise therapy supervised by an occupational therapist was performed eight times, and self-training was performed five times. Exercise intensity was monitored using the Borg Scale for subjective evaluation and the Karvonen formula for objective evaluation. Supervised exercise therapy with an occupational therapist resulted in greater increases on the Borg Scale and Karvonen formula than did self-training. It also induced increases in white blood cells and neutrophils. Her psychiatric symptoms improved, and she was discharged on Day 71. A blood test taken after discharge revealed that her white blood cell and neutrophil counts were within the normal range and she continued to take clozapine for 2 years. She has since been able to enjoy a calm and relaxed life at home.<br> Conclusion: Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self-exercise is insufficient for continuing clozapine treatment. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1742-6588 2892 2024 Crystal Grain Rotation during Tensile Test of Polycrystalline Pure Titanium Thin Sheet Based on Surface Height and Crystal Orientation 012002 EN Naoya Tada Okayama University Hiroaki Ohashi Okayama University Takeshi Uemori Okayama University Junji Sakamoto Okayama University Thin sheets and wires of polycrystalline pure titanium are important materials for various devices used in electrical, mechanical, dental, and medical fields. Since pure titanium shows strong anisotropy in elastic and plastic deformation, and the individual grains comprising a polycrystalline body have different orientations and geometries, inhomogeneous deformation always occurs on the microscopic scale. This inhomogeneity is more significant in thin films than in bulk materials. It is therefore important to investigate the inhomogeneous deformation of pure titanium thin sheets to ensure the reliability of various titanium devices. In this study, thin-sheet specimens made of polycrystalline pure titanium were subjected to tensile testing. Inhomogeneous deformation was evaluated on the basis of two kinds of crystal grain rotations based on surface height and crystal orientation. The results under elastic and plastic tensile conditions were compared. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0002-0729 54 8 2025 Oestrogen replacement combined with resistance exercise in older women with knee osteoarthritis: a randomised, double-blind, placebo-controlled clinical trial afaf224 EN Tomohiro Mitoma Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Hikaru Ooba Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Kasumi Takahashi Obstetrics and Gynecology, Ochiai Hospital Tsunemasa Kondo Obstetrics and Gynecology, Ochiai Hospital Tomohiro Ikeda Rehabilitation Medicine, Okayama University Hospital Yoko Sakamoto Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Toshiharu Mitsuhashi Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Jota Maki Medical Development Field, Center for Innovative Clinical Medicine, Okayama University Background: Interventions targeting physical function decline in older women with knee osteoarthritis (KOA) are vital for healthy ageing. The additive benefits of combining oestrogen replacement therapy (ERT) with resistance exercise remain unclear.<br> Objective: To evaluate the additive effect of low-dose ERT on physical performance when combined with a muscle resistance exercise programme (MREP) in older women with KOA.<br> Design: This is a placebo-controlled, double-blind, randomised clinical trial.<br> Subjects: The subjects were community-dwelling women aged ≥65 years with chronic knee pain and KOA diagnosis.<br> Methods: Participants completed a 3-month MREP and were randomised to receive daily low-dose transdermal ERT (oestradiol 0.54 mg/day) or placebo. Outcomes were assessed at baseline, postintervention and 12 months later. The primary outcome was change in 30-second chair stand test (CS-30) score. Secondary outcomes included muscle mass, knee extension strength, walking performance, metabolic indicators, knee pain scale and 12-item short-form health survey (SF-12). Between-group differences in CS-30 changes were analysed using a linear regression model based on the intention-to-treat principle.<br> Results: Among 168 individuals screened, 75 participants (mean age 73.8 years, SD 5.8) were enrolled and randomised into an ERT group (n = 37) or a placebo group (n = 38). Baseline CS-30 scores were 14.81 (SD 3.95) in the ERT group and 15.58 (SD 3.48) in the placebo group. At 3 months, mean changes were 2.59 (SD 2.58) and 1.79 (SD 2.28) repetitions, respectively. The primary analysis showed no statistically significant between-group difference [regression coefficient: 0.81 (95% CI: −0.31, 1.92); P = .16]. Post hoc subgroup and sensitivity analyses suggested that benefits may exist among early-stage KOA participants. SF-12 mental health scores also improved significantly in the ERT group. No serious adverse events occurred.<br> Conclusions: ERT did not confer significant additive benefits to resistance exercise overall but may improve outcomes in early-stage KOA and mental health domains. These exploratory findings warrant further investigation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Study of Periprosthetic Femoral Stem Fractures in Hip Arthroplasty for Femoral Neck Fracture 253 259 EN Yoshiaki Miyake Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Toru Takagi Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Taizo Konishiike Department of Orthopaedic Surgery, Japanese Red Cross Okayama Hospital Original Article 10.18926/AMO/69150 This study investigated the risk factors for bone fragility and perioperative periprosthetic femoral stem fractures in patients undergoing hip arthroplasty for femoral neck fractures. The records of 215 patients (42 male, 173 female; mean age, 84.4 years) were analyzed to assess correlations among periprosthetic fracture rates and sex, age, body mass index (BMI), Dorr classification, femoral stem fixation type (cemented/cementless), and bone mineral density (BMD) of the contralateral proximal femur. The overall prevalence of perioperative periprosthetic fractures was 4.7%. All patients with periprosthetic fractures were female, and all but one were ≥ 80 years of age. Fracture rates were higher in patients with lower BMI, although this difference was not significant. The fracture rates were 0%, 4.7%, and 7.9% for Dorr types A, B, and C, respectively, and 0% and 5.3% for patients who received cemented and cementless stems, respectively. The findings indicated that female patients, those of advanced age, those with lower BMI, and those with Dorr type C had lower BMDs. Although BMD was significantly lower in patients who received cemented stems compared to those who received cementless stems, no fractures were observed in the former group, suggesting that the use of cemented stems is safe for this high-risk population. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Organ Donation after Extracorporeal Cardiopulmonary Resuscitation: Clinical and Ethical Perspectives 221 229 EN Tetsuya Yumoto Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Kosaki Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Ageta Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/69147 Extracorporeal cardiopulmonary resuscitation (ECPR) has evolved into a life-saving therapy for select cardiac arrest patients, yet a growing body of evidence suggests it also holds promise as a bridge to organ donation in non-survivors. This review explores the clinical outcomes, ethical complexities, and evolving policies surrounding organ donation after ECPR. We summarize recent international and Japanese data demonstrating favorable graft function from ECPR donors, with the exception of lung transplantation. The ethical challenges ― particularly those involving brain death determination on extracorporeal membrane oxygenation and adherence to the dead donor rule ― are discussed in the context of Japan’s recent regulatory reforms. Additionally, we highlight the importance of structured end-of-life communication through multidisciplinary team meetings in facilitating ethically sound transitions from rescue efforts to donation pathways. Moving forward, improvements in donor management, standardized legal frameworks, and public and professional education are essential to optimizing the life-saving and life-giving potential of ECPR. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 3 2025 Association of the expression of 5‑FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S‑1 adjuvant chemotherapy: Follow‑up results of the Setouchi Lung Cancer Group Study 1201 79 EN Junichi Soh Department of Thoracic Surgery, Okayama University Hospital Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenicehi Gemba Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima 720‑0001, Japan; 8Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terasaki Department of Respiratory Surgery, Saga Medical Center Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center Masaaki Inoue Department of Thoracic Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Yuta Takahashi Department of Thoracic Surgery, Okayama University Hospital Hidejiro Torigoe Department of Thoracic Surgery, Okayama University Hospital Hiroki Sato Department of Thoracic Surgery, Okayama University Hospital Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Managing elderly patients presents several challenges because of age‑related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non‑small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5‑fluorouracil (5‑FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5‑FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S‑1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5‑FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross‑complementation group 1 (ERCC1), were assessed via quantitative reverse‑transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S‑1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that TS expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that EGFR upregulation and TS downregulation were correlated with favorable recurrence‑free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. EGFR mutations were associated with upregulation of DPD and EGFR, and downregulation of TS and ERCC1. In conclusion, although pathological stage is an independent prognostic factor for survival, EGFR upregulation and TS downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S‑1 adjuvant chemotherapy. The age‑related decrease in TS expression supports the potential benefit of 5‑FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2452-3216 68 2025 Method for predicting crack size using amplitude change in titanium alloy under bending vibration 1319 1323 EN Junji Sakamoto Okayama University, Faculty of Environmental, Life, Natural Science and Technology Naoya Tada Okayama University, Faculty of Environmental, Life, Natural Science and Technology Takeshi Uemori Okayama University, Faculty of Environmental, Life, Natural Science and Technology The natural frequency of a material decreases owing to the presence of cracks. Thus, when a crack initiates in a material under vibration, the amplitude of the vibration changes with the crack propagation. In this study, we investigated a method for predicting crack size using the amplitude change in a plate specimen of a titanium alloy under bending vibration. The bending displacement amplitudes were measured using high-speed camera images of the specimens. The crack sizes were measured using optical microscopy images of plastic replicas of the specimen surfaces that were obtained after interrupting tests at specified intervals. By using the relationship between the total area of the cracks and bending displacement amplitude for tests at two different vibration frequencies as well as the relationship between the vibration frequency and bending displacement amplitude for an undamaged specimen, the bending displacement amplitude at any vibration frequency can be monitored to predict the total area of the cracks. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-0102 218 2025 Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice 104922 EN Hoang Duy Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Miyazaki Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Anorexia nervosa (AN) is an eating disorder characterized by restricted energy intake, severely underweight status, and frequent hyperactivity. Previous research has shown structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus of AN patients. To investigate the pathological mechanism of AN, we analyzed the expression and distribution of parvalbumin (PV) interneurons and perineuronal nets (PNNs), which are implicated in the pathology of neuropsychiatric disorders, in the mPFC and hippocampus dorsal (HPCd) and ventral (HPCv) using an activity-based anorexia (ABA) mouse model. We found that PNN expression and density increased in the mPFC, with minor alterations in the HPCd and HPCv of ABA mice. The expression and distribution of PV neurons were unchanged in the brains of ABA mice, except for a regional decrease in PV-expressing neuron density in the HPCd. Co-localization analysis showed an increased number of PNNs enwrapping PV-negative neurons in the mPFC of ABA mice. Furthermore, the upregulation of PNN expression in the mPFC was positively correlated with elevated blood corticosterone levels, a well-known stress indicator, in ABA mice. Our findings suggest that the increased expression and distribution of PNNs surrounding PV-negative neurons in the mPFC may indicate the pathological mechanisms of AN. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0960-9822 35 12 2025 Oxytocin facilitates human touch-induced play behavior in rats 2916 2926.e3 EN Himeka Hayashi Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Sayaka Tateishi Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ayumu Inutsuka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Sho Maejima Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Hagiwara Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg Yasuo Sakuma Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Nippon Medical School Tatsushi Onaka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Valery Grinevich Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, German Center for Psychiatry (DZPG), Medical Faculty Mannheim, University of Heidelberg Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Pleasant touch sensations play a fundamental role in social bonding, yet the neural mechanisms underlying affinity-like behaviors remain poorly understood. Here, we demonstrate that juvenile-adolescent rats, which naturally engage in social play with peers characterized by rough-and-tumble interactions and 50 kHz ultrasonic vocalizations indicating pleasant sensations, develop a strong affinity for human hands through similar playful contact achieved by repeated tickling with human hands. Using this rat with tickling-induced high affinity for human hands, we discovered that repeated tickling mimicking rough-and-tumble play led to increased oxytocin receptor (OTR) expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl). Inhibition of oxytocin signaling in the VMHvl reduced affinity-like behaviors from rats to human hands. These findings suggest that OTR neurons in VMHvl play an important role in the increase in affinity for human hands induced by pleasant touch sensation with human touch-induced play behavior. Based on retrograde and anterograde tracing studies examining the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) as primary sources of oxytocin, we demonstrate that a subset of oxytocin fibers in the VMHvl originate from the SON, suggesting that affinity-like behavior from rats to human hands may be controlled by oxytocin signaling from magnocellular neurons. Together, this work advances our understanding of how oxytocin shapes social behavior and may inform the development of therapeutic strategies to promote positive social interactions. 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.

Wiley Acta Medica Okayama 2769-2558 4 2 2025 Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report e70091 EN Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Yuko Nakamura Department of Neuropsychiatry, Okayama University Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.<br> Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.<br> Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 2 2025 A case report of ineffective electroconvulsive therapy for chronic pain e70108 EN Takashi Fukao Department of Neuropsychiatry, Okayama University Hospital Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Yuto Yamada Department of Neuropsychiatry, Okayama University Hospital Kazushi Asada Department of Neuropsychiatry, Okayama University Hospital Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Hirotoshi Ri Department of Neuropsychiatry, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective.<br> Case Presentation: The patient was a 63-year-old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted.<br> Conclusion: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last-resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision-making based on accurate information is vital. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Lower Work Engagement Is Associated with Insomnia, Psychological Distress, and Neck Pain among Junior and Senior High School Teachers in Japan 93 100 EN Rina Tsuchie 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 Hideki Tsumura Department of Psychology, Graduate School of Technology, Industrial and Social Sciences, Tokushima University Minako Kinuta Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Hisamatsu Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68647 School teachers are subject to both physical and mental health problems. We examined cross-sectional relationships between work engagement and major health outcomes among junior and senior high school teachers in Japan via a nationwide survey in 2019-2020. A total of 3,160 respondents were included in the analyses (19.9% response rate). Work engagement was assessed with the Utrecht Work Engagement Scale-9 (UWES-9), and we thus divided the teachers into quartiles according to their UWES-9 scores. Based on validated questionnaires, we assessed insomnia, psychological distress, and neck pain as health outcomes. A binomial logistic regression adjusted for age, gender, school type, teacher’s roles, involvement in club activities, division of duties, employment status, and whether they lived with family demonstrated that the teachers with lower UWES-9 scores had higher burdens of insomnia, psychological distress, and neck pain (odds ratios [95% confidence intervals] in 4th vs. 1st quartile, 2.92 (2.34-3.65), 3.70 (2.81-4.88), and 2.12 (1.68-2.68), respectively; all trend p<0.001). There were no significant differences in these associations between full-time and part-time teachers. Our findings indicate that low work engagement may contribute to physical and mental health issues among junior and senior high school teachers, thus providing insights for preventing health problems in this profession. No potential conflict of interest relevant to this article was reported.

Department of Mathematics, Faculty of Science, Okayama University Acta Medica Okayama 0030-1566 67 1 2025 Locally serially coalescent classes of Lie algebras 67 74 EN Masanobu Honda Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Medical and Life Sciences Takanori Sakamoto Department of Mathematics, University of Teacher Education Fukuoka We assume that a basic field k has zero characteristic. We show that any Fitting class is serially coalescent for locally finite Lie algebras. We also show that any class X satisfying N ≤ X ≤ ˆGr (e.g. Ft, B, Z, Gr, lN, rN, `e(◁)ˆA, ˆe(◁)ˆA, `Gr) is locally serially coalescent for locally finite Lie algebras, and, for any locally finite Lie algebra L, the X-ser radical of L is locally nilpotent. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2041-1723 16 1 2025 Keratinocyte-driven dermal collagen formation in the axolotl skin 1757 EN Ayaka Ohashi Graduate School of Environment, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Graduate School of Environment, Life, Natural Science and Technology, Okayama University Junpei Kuroda Graduate School of Frontier Biosciences, Osaka University Yohei Kondo Center for One Medicine Innovative Translational Research (COMIT), Nagoya University Yasuhiro Kamei Laboratory for Biothermology, National Institute for Basic Biology Shigenori Nonaka The Graduate University for Advanced Studies (SOKENDAI) Saya Furukawa Graduate School of Environment, Life, Natural Science and Technology, Okayama University Sakiya Yamamoto Graduate School of Environment, Life, Natural Science and Technology, Okayama University Akira Satoh Graduate School of Environment, Life, Natural Science and Technology, Okayama University Type I collagen is a major component of the dermis and is formed by dermal fibroblasts. The development of dermal collagen structures has not been fully elucidated despite the major presence and importance of the dermis. This lack of understanding is due in part to the opacity of mammalian skin and it has been an obstacle to cosmetic and medical developments. We reveal the process of dermal collagen formation using the highly transparent skin of the axolotl and fluorescent collagen probes. We clarify that epidermal cells, not dermal fibroblasts, contribute to dermal collagen formation. Mesenchymal cells (fibroblasts) play a role in modifying the collagen fibers already built by keratinocytes. We confirm that collagen production by keratinocytes is a widely conserved mechanism in other model organisms. Our findings warrant a change in the current consensus about dermal collagen formation and could lead to innovations in cosmetology and skin medication. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 1 2025 A case of invasive pulmonary aspergillosis associated with clozapine-induced agranulocytosis e70077 EN Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Masaki Fujiwara Department of Neuropsychiatry, Okayama University Hospital Toshiki Terao Department of Hematology and Oncology, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Hospital Yuto Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ryota Sato Okayama Psychiatric Medical Center Momoko Mishima Okayama Psychiatric Medical Center Yuji Yada Okayama Psychiatric Medical Center Ken-Ichi Matsuoka Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Clozapine-induced agranulocytosis (CLIA) is a rare but serious complication. Fever associated with CLIA is typically treated with broad-spectrum antimicrobials, but empiric antifungal therapy is rarely used. While bacterial and viral infections have been reported in CLIA cases, no cases of fungal infections complicated by CLIA have been documented. We report the first case of CLIA complicated by invasive pulmonary aspergillosis (IPA) in a patient with schizophrenia. The diagnosis of IPA was made using serum beta-D-glucan, Aspergillus galactomannan antigen tests, and chest computed tomography (CT). <br> Case presentation: We present a case of a 51-year-old man with schizophrenia who developed CLIA complicated by IPA. The patient, diagnosed with treatment-resistant schizophrenia, was started on clozapine, but 9 months later he presented with fever, cough, leukopenia, and neutropenia. Clozapine was discontinued, and empirical treatments with cefepime and filgrastim were initiated. Serum beta-D-glucan and Aspergillus galactomannan antigen tests were positive, and chest CT showed well-circumscribed nodules, leading to a probable diagnosis of IPA. Antifungal therapy was switched from micafungin to voriconazole according to guidelines. His neutropenia and fever improved, and he was re-transferred to a psychiatric hospital. <br> Conclusion: CLIA can be complicated by fungal infections. When patients with CLIA present with fever, fungal infections, including IPA, should be considered in the differential diagnosis. Serological tests, including beta-D-glucan and Aspergillus galactomannan, are useful for the diagnosis of IPA as well as the appropriate use of antifungal agents in patients with CLIA. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 4 2025 Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study 1391 EN Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobuyoshi Matsuki Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoko Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Keigo Ueda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Matsuda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Takase Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Omura Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1756-4646 125 2025 Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways 106672 EN Saki Okamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Saya Kakimaru Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mayuko Koreishi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mika Sakamoto National Institute of Genetics, ROIS Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Hideya Ando Department of Applied Chemistry and Biotechnology, Okayama University of Science Yoshio Tsujino Graduate School of Science, Technology, and Innovation, Kobe University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0941-1291 2024 Optimization of workflow processes for sustainable paternal involvement: case study of an academic “daddy surgeon” in Japan EN Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshitaka Kondo Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuko Takehara Department of Surgery, Okayama Saiseikai General Hospital Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Minagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masaki Sakamoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitomi Kataoka Integrated Clinical Education Center, Kyoto University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Work–life balance is often discussed in Japan. Yet surgeons find it challenging to take paternity leave because of their demanding surgical duties and a strong sense of responsibility. One Japanese male surgeon had his first paternity experience as a research fellow in the US. When he returned to Japan, he resumed his surgical training and started a research project to become an academic surgeon. When he and his wife were expecting their second child, they discussed his paternity participation before the delivery and decided on a sustainable paternity participation plan. By coordinating his responsibilities with his co-workers, he limited his attendance at work to daytime hours only for 1 month to manage paternity duties. This adjustment did not affect the number of main and assistant operations conducted that month and effective optimization of workflow processes decreased the extra workload for other team members. His experience suggests that the optimization of workflow processes can enhance personal life, including paternity participation. (150/150). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Traumatic Neuroma Arising from Surgical Trauma during Conversion from Laparoscopic to Open Cholecystectomy 459 464 EN Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, 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 Case Report 10.18926/AMO/67872 Traumatic neuroma is an abnormal proliferation of injured nerves resulting from trauma or surgery. We present a case of traumatic neuroma arising in the cystic duct after cholecystectomy. A 66-year-old man was referred to our department due to a biliary tumor. He had undergone cholecystectomy 20 years prior. Cholangioscopy showed an elevated lesion covered with smooth mucosa. Histological examination revealed normal bile duct mucosa. Although benign disease was suspected, the possibilities of malignant disease could not be excluded. Extrahepatic bile duct resection was planned to include intraoperative rapid-freezing of a biopsy specimen followed by histopathological examination. These intraoperative histology results showed proliferation of nerve and fibrous tissue only, resulting in the diagnosis of traumatic neuroma, so no lymph nodes were removed. To avoid excessive surgical intervention, histopathological examination of an intraoperative rapid-frozen biopsy specimen may be important for diagnosing traumatic neuroma. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 10 2024 The protective effect of carbamazepine on acute lung injury induced by hemorrhagic shock and resuscitation in rats e0309622 EN Yaqiang Li Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University Medical School Yifu Lu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Sakamoto Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emiko Omori Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Takahashi Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-alpha and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0085-2538 106 5 2024 A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope 972 984 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J.L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Kota Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiromi Kuramoto Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual’s change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, −30.8% (95% confidence interval −42.6 to −16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Occult Nesidioblastosis Detected by 111In-Pentetreotide Single-Photon Emission Computed Tomography 423 428 EN Shinya Sakamoto Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenteorlogical Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Ai Hishida Department of Endocrinology and Metabolism, 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 Gastroenteorlogical Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/67667 Nesidioblastosis, also known as persistent hyperinsulinemic hypoglycemia, is usually observed in children and infants, although more recently adult-onset nesidioblastosis has also been described. We present a case of nesidioblastosis in a 78-year-old man that was detected by 111In-pentetreotide single photon emission computed tomography (SPECT/CT). The patient was transferred to our hospital’s emergency department in a hypoglycemic coma. Dynamic enhanced CT could detect no lesion in the pancreas, but an 111In-pentetreotide SPECT/CT scan performed after a similar episode four weeks later showed increased focal uptake at the head of the pancreas. The results of a selective arterial calcium injection test were negative. After careful consideration and discussion among colleagues, surgical intervention was selected, and a pancreaticoduodenectomy was performed. On histology, there were elevated numbers of Langerhans islets in the pancreatic head, and the islets themselves appeared enlarged. Hypertrophic β-cells comprised the majority, but α-cells, δ-cells and pancreatic polypeptide were also detected in the islets. Based on the histopathological results and repeated hyperinsulinemic hypoglycemic crises, the patient was finally diagnosed with adult-onset nesidioblastosis. He had no hypoglycemic symptoms during outpatient follow-up examination. Since 111In-pentetreotide SPECT/CT may be able to detect nesidioblastosis, clinicians should consider this relatively new-modality examination when encountering such cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Prognostic Efficacy of the Albumin Grade in Patients with Hepatocellular Carcinoma 377 386 EN Yuichi Hirano Department of Gastroenterology, Okayama City Hospital Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Kazuya Kariyama Department of Gastroenterology, Okayama City Hospital Atsushi Hiraoka Gastroenterology Center, Ehime Prefectural Central Hospital Shohei Shiota Department of Gastroenterology, Okayama City Hospital Akiko Wakuta Department of Gastroenterology, Okayama City Hospital Satoshi Yasuda Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital Hidenori Toyoda Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital Kunihiko Tsuji Center of Gastroenterology, Teine Keijinkai Hospital Takeshi Hatanaka Department of Gastroenterology, Saiseikai Maebashi Hospital Satoru Kakizaki Department of Clinical Research, NHO Takasaki General Medical Center Atsushi Naganuma Department of Gastroenterology, NHO Takasaki General Medical Center Toshifumi Tada Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Ei Itobayashi Department of Gastroenterology, Asahi General Hospital Toru Ishikawa Department of Gastroenterology, Saiseikai Niigata Hospital Noritomo Shimada Division of Gastroenterology and Hepatology, Otakanomori Hospital Koichi Takaguchi Department of Hepatology, Kagawa Prefectural Central Hospital Akemi Tsutsui Department of Hepatology, Kagawa Prefectural Central Hospital Takuya Nagano Department of Hepatology, Kagawa Prefectural Central Hospital Michitaka Imai Department of Gastroenterology, Niigata Cancer Center Hospital Shinichiro Nakamura Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Takashi Kumada Department of Nursing, Gifu Kyoritsu University Real-Life Practice Experts for HCC (RELPEC) Study Group in Japan Original Article 10.18926/AMO/67662 We previously found that “albumin grade”, formerly called the “ALBS grade,” demonstrated significant capability for prognostic stratification in hepatocellular carcinoma (HCC) patients treated with lenvatinib. The purpose of the present study was to compare the performance of the albumin grade with that of the modified albumin-bilirubin (mALBI) grade in predicting overall survival of HCC patients with different BCLC stages and treatment types. We enrolled 7,645 Japanese patients newly diagnosed with HCC using the Akaike information criteria (AIC), likelihood ratio, and C-index in different Barcelona Clinic Liver Cancer (BCLC) stages and treatments. The albumin grade showed similar and slightly better performance than the mALBI grade for BCLC stage 0 and A and especially for patients who underwent curative surgery and ablation. In patients treated with transcatheter arterial chemoembolization, molecular targeted agents, and the best supportive care, the mALBI grade had better performance than the albumin grade. However, the differences of the indices were very small in all scenarios. Overall, the albumin grade was comparable in efficacy to the mALBI grade, showing particular benefit for patients with early-stage HCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital 371 376 EN Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Miyoshi Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University I Putu Bayu Mayura Department of Clinical Microbiology, Faculty of Medicine, Udayana University Shuma Tsuji Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shinnosuke Fukushima 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 Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Original Article 10.18926/AMO/67657 Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control. No potential conflict of interest relevant to this article was reported.

Anticancer Research USA Inc. Acta Medica Okayama 1109-6535 21 5 2024 Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells 464 473 EN TAIRA HIROSE Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences YUKI KUNISADA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KOICHI KADOYA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences HIROKI MANDAI Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science YUMI SAKAMOTO Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KYOICHI OBATA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KISHO ONO Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences HIROAKI TAKAKURA Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences KAZUHIRO OMORI Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University SHOGO TAKASHIBA Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University SEIJI SUGA Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University SOICHIRO IBARAGI Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background/Aim: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. Materials and methods: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. Results: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. Conclusion: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 136 2 2024 令和５年度岡山医学会賞　総合研究奨励賞（結城賞） 48 50 EN Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 3 3 2024 Forgetfulness in adult attention-deficit/hyperactivity disorder masks transient epileptic amnesia: a case report e70003 EN Takashi Fukao Department of Neuropsychiatry, OkayamaUniversity Hospital Masaki Fujiwara Department of Neuropsychiatry, OkayamaUniversity Hospital Yuto Yamada Department of Neuropsychiatry, OkayamaUniversity Hospital Shinji Sakamoto Department of Neuropsychiatry, OkayamaUniversity Hospital Yosuke Matsumoto Okayama University Hospital Gender Center Manabu Takaki Department of Neuropsychiatry, OkayamaUniversity Faculty of Medicine, Dentistry andPharmaceutical Sciences Background: Inattention due to attention-deficit/hyperactivity disorder (ADHD) can lead to forgetfulness. Transient epileptic amnesia (TEA) can cause forgetfulness, similar to ADHD. We report a patient with ADHD who developed TEA.<br> Case Presentation: The patient was a 40-year-old woman with ADHD. She has been prone to forgetfulness since childhood. Two years before visiting our outpatient clinic, she had begun to occasionally forget events that had occurred several days earlier. However, she was largely unaware of the emergence of new amnestic symptoms. She had also begun to experience various other amnestic symptoms 2 months before she visited our clinic, which prompted her to visit our outpatient clinic. The combination of a detailed interview, electroencephalography (EEG) examination, and consideration of TEA enabled us to diagnose her with TEA and provide treatment accordingly. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA.<br> Conclusion: Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness. We report a patient with ADHD who developed TEA. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA. Psychiatrists need to consider TEA when patients with ADHD present with changes or exacerbation of forgetfulness. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 4 2024 Can Pelvic Lymph Node Dissection in Prostate Cancer Patients with a 5% Briganti Nomogram Cut-off Value Provide an Oncological Benefit? A Large Multi-Institutional Cohort Study in Japan 307 312 EN Naoya Sugihara Department of Urology, Ehime University Katsuyoshi Hashine Department of Urology, National Hospital Organization Shikoku Cancer Center Natsumi Yamashita Division of Epidemiology, National Hospital Organization Shikoku Cancer Center Miki Sakamoto Department of Urology, Ehime University Masato Terashita Department of Urology, Ehime University Keisuke Funaki Department of Urology, Ehime University Kaori Saiki Department of Urology, Ehime University Takatora Sawada Department of Urology, Ehime University Toshio Kakuda Department of Urology, Ehime University Kenichi Nishimura Department of Urology, Ehime University Tetsuya Fukumoto Department of Urology, Ehime University Noriyosi Miura Department of Urology, Ehime University Yuki Miyauchi Department of Urology, Ehime University Tadahiko Kikugawa Department of Urology, Ehime University Takashi Saika Department of Urology, Ehime University Original Article 10.18926/AMO/67546 The Briganti nomogram (cut-off value 5%) is commonly used to determine the indications for pelvic lymph node dissection (PLND) in patients with prostate cancer. We retrospectively analyzed the potential oncological benefit of PLND based on the 5% cut-off value on the Briganti nomogram. We obtained the data from the Medical Investigation Cancer Network (MICAN) Study, which included 3,463 patients who underwent a radical prostatectomy (RP) at nine institutions in Japan between 2010 and 2020. We included patients with Briganti scores ≥ 5% and a follow-up period ≥6 months and excluded patients categorized in the very high-risk group (based on NCCN categories); a final total of the cases of 1,068 patients were analyzed. The biochemical recurrence (BCR)-free survival was significantly worse in the patients who underwent PLND compared to those who did not (p=0.019). A multivariate analysis showed that high prostate-specific antigen (PSA) levels (p<0.001) and an advanced T-stage (p=0.018) were significant prognostic factors for BCR, whereas PLND had no effect on BCR (p=0.059). Thus, PLND in patients with prostate cancer whose Briganti score was 5% did not provide any oncological benefit. Further research is necessary to determine the indication criteria for conducting PLND. No potential conflict of interest relevant to this article was reported.

Mary Ann Liebert Acta Medica Okayama 2689-2820 5 1 2024 Factors Associated with Differences in Physicians’ Attitudes toward Percutaneous Endoscopic Gastrostomy Feeding in Older Adults Receiving End-of-Life Care in Japan: A Cross-Sectional Study 206 214 EN Yoko Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Background: Although percutaneous endoscopic gastrostomy (PEG) placement is still widely practiced in Japan, studies from Western countries report that it is less beneficial for patients in end-of-life care with cognitive decline. Decisions regarding PEG placement are largely influenced by physician judgment.<br> Objectives: The aim of this study was to investigate the background and perceptions of Japanese physicians regarding PEG for older adults in end-of-life care and to identify the factors associated with differences in physician judgment regarding PEG.<br> Design: The study employed a cross-sectional design.<br> Setting/Subjects: A questionnaire on PEG for older adults in end-of-life care was sent to Japanese physicians. Logistic regression analysis was used to calculate the odds ratios (ORs) and confidence intervals (CIs) of the association between PEG recommendations and each factor.<br> Results: PEG placement was advised for bedridden patients and older adults with cognitive decline by 26% of the physicians who responded to the survey. Differences in physician perceptions of PEG feeding were associated with the recommendation for PEG, benefits of preventing aspiration pneumonia (OR: 4.9; 95% CI: 3.1-8.2), impact on post-discharge accommodation decisions (OR: 6.1; 95% CI: 1.9-30.9), and hesitancy to recommend a PEG placement (OR: 1.9; 95% CI: 1.3-4.5). Working in a facility with PEG placement (OR: 2.0; 95% CI: 1.2-3.5) was an associated background factor.<br> Conclusions: Differences in Japanese physicians' attitudes toward using PEG feeding for older adults in end-of-life care were significantly associated with differences in their perceptions of the impact of PEG feeding and working in a facility with PEG placement. No potential conflict of interest relevant to this article was reported.

Japan Society of Mechanical Engineers Acta Medica Okayama 2187-9745 11 6 2024 Effect of artificial defect on tensile properties of thin titanium alloy wire 24-00129 EN Junji SAKAMOTO Okayama University Naoya TADA Okayama University Takeshi UEMORI Okayama University Koyo OISHI Okayama University This study investigated the effects of artificial defects, introduced via focused ion beam (FIB) processing, on the tensile properties of thin titanium alloy wires (Ti-6Al-4V). Results indicated that the defective wires fractured when the net-section nominal stress reached the ultimate tensile strength of the smooth wires, probably because of localized stress concentrations relaxing due to plastic deformation around the defects. The effect of defects on tensile properties was classified into three regions based on the size of the defect area. In the case of small defects, wires fractured at the smooth area away from the defects where the cross-sectional strength was lower. In this case, the defects minimally affected the tensile properties. This is attributable to variations in the cross-sectional strength of the wire, which resulted in some sections with lower strength as compared with the defect area. In the case of medium-sized defects, the fracture strain decreased gradually as the defect area increased. Finally, in the case of large defects, the fracture strain was extremely small. The boundary between the medium-sized and large defects indicates the transition from plastic deformation to no plastic deformation in the smooth area. No potential conflict of interest relevant to this article was reported.

Zoological Society of Japan Acta Medica Okayama 0289-0003 41 3 2024 Volume X-Ray Micro-Computed Tomography Analysis of the Early Cephalized Central Nervous System in a Marine Flatworm, Stylochoplana pusilla 281 289 EN Takanori Ikenaga Graduate School of Science and Engineering, Kagoshima University Aoshi Kobayashi Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihisa Takeuchi Japan Synchrotron Radiation Research Institute/SPring-8 Kentaro Uesugi Japan Synchrotron Radiation Research Institute/SPring-8 Takanobu Maezawa Department of Integrated Science and Technology, National Institute of Technology, Tsuyama College Norito Shibata Department of Integrated Science and Technology, National Institute of Technology, Tsuyama College Tatsuya Sakamoto Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Platyhelminthes are a phylum of simple bilaterian invertebrates with prototypic body systems. Compared with non-bilaterians such as cnidarians, the bilaterians are likely to exhibit integrated free-moving behaviors, which require a concentrated nervous system “brain” rather than the distributed nervous system of radiatans. Marine flatworms have an early cephalized ‘central’ nervous system compared not only with non-bilaterians but also with parasitic flatworms or freshwater planarians. In this study, we used the marine flatworm Stylochoplana pusilla as an excellent model organism in Platyhelminthes because of the early cephalized central nervous system. Here, we investigated the three-dimensional structures of the flatworm central nervous system by the use of X-ray micro-computed tomography (micro-CT) in a synchrotron radiation facility. We found that the obtained tomographic images were sufficient to discriminate some characteristic structures of the nervous system, including nerve cords around the cephalic ganglion, mushroom body-like structures, and putative optic nerves forming an optic commissure-like structure. Through the micro-CT imaging, we could obtain undistorted serial section images, permitting us to visualize precise spatial relationships of neuronal subpopulations and nerve tracts. 3-D micro-CT is very effective in the volume analysis of the nervous system at the cellular level; the methodology is straightforward and could be applied to many other non-model organisms. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 高齢外来患者における欠損補綴歯科治療法，食品摂取多様性スコアおよび摂取可能食品スコアとの関連 EN Kazuki SAKAMOTO Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model EN Daiki TAKEZAKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

The Japan Society of Histochemistry and Cytochemistry Acta Medica Okayama 0044-5991 57 2 2024 Membrane-Targeted palGFP Predominantly Localizes to the Plasma Membrane but not to Neurosecretory Vesicle Membranes in Rat Oxytocin Neurons 85 88 EN Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ayumu Inutsuka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Recent advances in viral vector technology, specifically using adeno-associated virus (AAV) vectors, have significantly expanded possibilities in neuronal tracing. We have utilized the Cre/loxP system in combination with AAV techniques in rats to explore the subcellular localization of palmitoylation signal-tagged GFP (palGFP) in oxytocin-producing neurosecretory neurons. A distinctive branching pattern of single axons was observed at the level of the terminals in the posterior pituitary. Despite challenges in detecting palGFP signals by fluorescent microscopy, immunoelectron microscopy demonstrated predominant localization on the plasma membrane, with a minor presence on the neurosecretory vesicle membrane. These findings suggest that membrane-anchored palGFP may undergo exocytosis, translocating from the plasma membrane to the neurosecretory vesicle membrane. In this study, we observed characteristic axon terminal structures in the posterior pituitary of oxytocin neurons. This study indicates the importance of understanding the plasma membrane-specific sorting system in neuronal membrane migration and encourages future studies on the underlying mechanisms. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 65 4 2023 Plastid Inheritance Revisited: Emerging Role of Organelle DNA Degradation in Angiosperms 484 492 EN Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Plastids are essential organelles in angiosperms and show non-Mendelian inheritance due to their evolution as endosymbionts. In approximately 80% of angiosperms, plastids are thought to be inherited from the maternal parent, whereas other species transmit plastids biparentally. Maternal inheritance can be generally explained by the stochastic segregation of maternal plastids after fertilization because the zygote is overwhelmed by the maternal cytoplasm. In contrast, biparental inheritance shows the transmission of organelles from both parents. In some species, maternal inheritance is not absolute and paternal leakage occurs at a very low frequency (∼10−5). A key process controlling the inheritance mode lies in the behavior of plastids during male gametophyte (pollen) development, with accumulating evidence indicating that the plastids themselves or their DNAs are eliminated during pollen maturation or at fertilization. Cytological observations in numerous angiosperm species have revealed several critical steps that mutually influence the degree of plastid transmission quantitatively among different species. This review revisits plastid inheritance from a mechanistic viewpoint. Particularly, we focus on a recent finding demonstrating that both low temperature and plastid DNA degradation mediated by the organelle exonuclease DEFECTIVE IN POLLEN ORGANELLE DNA DEGRADATION1 (DPD1) influence the degree of paternal leakage significantly in tobacco. Given these findings, we also highlight the emerging role of DPD1 in organelle DNA degradation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 A Case of Gallbladder Cancer with Trousseau Syndrome Successfully Treated Using Radical Resection 201 204 EN Akari Masunaga Department of Gastroenterological Surgery, Kochi Health Sciences Center Motoyasu Tabuchi Department of Gastroenterological Surgery, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Rika Yoshimatsu Department of Radiology, Kochi Health Sciences Center Manabu Matsumoto Department of Radiology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/66931 Trousseau syndrome is characterized by cancer-associated systemic thrombosis. We describe the first case of a successfully treated gallbladder adenocarcinoma accompanied by Trousseau syndrome. A 66-year-old woman presented with right hemiplegia. Magnetic resonance imaging identified multiple cerebral infarctions. Her serum carbohydrate antigen 19-9 and D-dimer levels were markedly elevated, and a gallbladder tumor was detected via abdominal computed tomography. Venous ultrasonography of the lower limbs revealed a deep venous thrombus in the right peroneal vein. These findings suggested that the brain infarctions were likely caused by Trousseau syndrome associated with her gallbladder cancer. Radical resection of the gallbladder tumor was performed. The resected gallbladder was filled with mucus and was pathologically diagnosed as an adenocarcinoma. Her postoperative course was uneventful, and she received a one-year course of adjuvant therapy with oral S-1. No cancer recurrence or thrombosis was noted 26 months postoperatively. Despite concurrent Trousseau syndrome, a radical cure of the primary tumor and thrombosis could be achieved with the appropriate treatment. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 2 2024 Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane e0297347 EN Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Ishihara Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Tetsuro Morita Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Muraoka Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Koto Kyorin Eye Center, Department of Ophthalmology, Kyorin University School of Medicine Ryo Kawasaki Division of Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine Takayuki Baba Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine Fumiki Okamoto Department of Ophthalmology, Graduate School of Medicine, Nippon Medical School Makoto Inoue Kyorin Eye Center, Department of Ophthalmology, Kyorin University School of Medicine Taiji Sakamoto Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences Akitaka Tsujikawa Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background<br> Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries.<br> Methods and design<br> This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications.<br> Discussion<br> The results of this study will support the surgical decisions and procedures in ERM practices. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2223-7747 13 5 2024 The Impact of Phenological Gaps on Leaf Characteristics and Foliage Dynamics of an Understory Dwarf Bamboo, Sasa kurilensis 719 EN Chongyang Wu Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration Ryota Tanaka Faculty of Agriculture, Okayama University Kyohei Fujiyoshi Faculty of Agriculture, Okayama University Yasuaki Akaji Biodiversity Division, National Institute for Environmental Studies Muneto Hirobe Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University Naoko Miki Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University Juan Li Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration Keiji Sakamoto Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University Jian Gao Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration Phenological gaps exert a significant influence on the growth of dwarf bamboos. However, how dwarf bamboos respond to and exploit these phenological gaps remain enigmatic. The light environment, soil nutrients, leaf morphology, maximum photosynthetic rate, foliage dynamics, and branching characteristics of Sasa kurilensis were examined under the canopies of Fagus crenata and Magnolia obovata. The goal was to elucidate the adaptive responses of S. kurilensis to phenological gaps in the forest understory. The findings suggest that phenological gaps under an M. obovata canopy augment the available biomass of S. kurilensis, enhancing leaf area, leaf thickness, and carbon content per unit area. However, these gaps do not appreciably influence the maximum photosynthetic rate, total leaf number, leaf lifespan, branch number, and average branch length. These findings underscore the significant impact of annually recurring phenological gaps on various aspects of S. kurilensis growth, such as its aboveground biomass, leaf morphology, and leaf biochemical characteristics. It appears that leaf morphology is a pivotal trait in the response of S. kurilensis to phenological gaps. Given the potential ubiquity of the influence of phenological gaps on dwarf bamboos across most deciduous broadleaf forests, this canopy phenomenon should not be overlooked. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Utility of Combined Use of Transabdominal Ultrasonography and Fecal Immunochemical Test Examinations in Ulcerative Colitis 79 83 EN Masahiro Takahara 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 Masayasu Ohmori Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Takei Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Aoyama 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 Shoko Igawa 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 Junki Toyosawa 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 Keita Harada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Onishi 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 Short Communication 10.18926/AMO/66674 This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0007-0920 130 7 2024 Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus 1187 1195 EN Masashi Hashimoto 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 Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Kadowaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Hamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryoma Sugimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chiaki Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Ohtani Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kento Kumon Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi 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 Satoru Kikuchi 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 Hiroshi Tazawa 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 Takahito Yagi Department of Gastroenterological Surgery, 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 Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702).<br> Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps).<br> Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection.<br> Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer. No potential conflict of interest relevant to this article was reported.

eLife Sciences Publications Acta Medica Okayama 2050-084X 12 2023 Characterization of tryptophan oxidation affecting D1 degradation by FtsH in the photosystem II quality control of chloroplasts RP88822 EN Yusuke Kato Institute of Plant Science and Resources (IPSR), Okayama University Hiroshi Kuroda Research Institute for Interdisciplinary Science, Okayama University Shin-Ichiro Ozawa Institute of Plant Science and Resources (IPSR), Okayama University Keisuke Saito Research Center for Advanced Science and Technology, The University of Tokyo Vivek Dogra Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences Martin Scholz Institute of Plant Biology and Biotechnology, University of Münster Guoxian Zhang Institute of Plant Science and Resources (IPSR), Okayama University Catherine de Vitry Institut de Biologie Physico-Chimique, Unité Mixte de Recherche 7141, Centre National de la Recherche Scientifique and Sorbonne Université Pierre et Marie Curie Hiroshi Ishikita Research Center for Advanced Science and Technology, The University of Tokyo Chanhong Kim Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences Michael Hippler Institute of Plant Science and Resources (IPSR), Okayama University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Wataru Sakamoto Institute of Plant Science and Resources (IPSR), Okayama University Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1350-6307 153 2023 Prediction of slip activity of crystal grains around semi-circular and semi-elliptical notches in thin-sheet specimens of pure titanium using formulated macroscopic stress distribution and crystal orientation 107623 EN Naoya Tada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Uemori Faculty of Environmental, Life, Natural Science and Technology, Okayama University Junji Sakamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Thin metal sheets and wires are important materials for various devices used in electrical, mechanical, and medical fields. With the downsizing of these devices, demand for thinner sheets and wires has increased. Amongst the many metals available, pure titanium has been attracting much attention for use in medical and dental devices because of its good biocompatibility in addition to its light weight and high corrosion resistance. However, thin metal sheets and wires are usually polycrystalline materials and, with the downsizing of materials, there is a loss of homogeneity during deformations. Inhomogeneous deformation becomes significant in thin sheets and wires, owing to the different crystal orientations and geometries of crystal grains. Furthermore, the shapes of such devices are not uniform, unlike, say, a simple rod. Therefore, macroscopic stress and strain concentrations should be taken into consideration when designing these devices as they affect the localization of deformation and the resultant fracture. In this study, semi-circular and semi-elliptical notched specimens made of thin-sheet polycrystalline pure titanium are subjected to tensile testing. Inhomogeneous deformation caused by crystallographic slip is observed near the notch root. Analysis of the crystal orientation and observation of the slip line show that the slip initiation in crystal grains is affected by the macroscopic stress distribution and can be predicted from the slip activity calculated from both the critical resolved shear stress on the slip systems and the resolved shear stress acting on prospective slip planes obtained from the macroscopic multiaxial stress distribution. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Initial Outcomes of the Safe and Sound Protocol on Patients with Adult Autism Spectrum Disorder: Exploratory Pilot Study EN Hiroki KAWAI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-5155 67 3 2023 A nationwide survey of newly certified visually impaired individuals in Japan for the fiscal year 2019: impact of the revision of criteria for visual impairment certification 346 352 EN Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Morimoto Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kawasaki Department of Vision Informatics, Osaka University Graduate School of Medicine Miyuki Fujiwara Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keisuke Kanenaga Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidetoshi Yamashita Yamagata City Institute of Public Health Taiji Sakamoto Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose　To determine the status of visual impairment certification in Japan in the fiscal year 2019 and the impact of revising the criteria for visual impairment certification implemented in 2018.<br> Study Design　Observational cross-sectional study.<br> Methods　We requested welfare offices throughout Japan to submit data of age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years during the fiscal year 2019. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons.<br> Results　Altogether, data were collected for 16,504 newly certified visually impaired individuals. The most common age group was 80–89 years (29.6%), followed by 70–79 (28.2%) and 60–69 (15.3%) years. The most common causative disease was glaucoma (40.7%), followed by retinitis pigmentosa (13.0%), diabetic retinopathy (10.2%), and macular degeneration (9.1%). The most common impairment grade was grade 2 (40.8%), followed by 5 (21.2%) and 1 (17.0%). Compared to the fiscal year 2015, there was a considerable increase in the number of individuals certified with glaucoma in the fiscal year 2019. Moreover, there was a significant increase in the number of individuals with certified grades 1 and 2 visual impairment, with a decrease in the number of individuals with certified grade 6 visual impairment.<br> Conclusion　The changes revealed in this study were primarily due to the revised certification criteria implemented in July 2018, indicating that it is important to review the certification criteria and to repeat surveys similar to the present study. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-462X 14 2023 FZL, a dynamin-like protein localized to curved grana edges, is required for efficient photosynthetic electron transfer in Arabidopsis 1279699 EN Yu Ogawa Institute of Plant Science and Resources, Okayama University Megumi Iwano Graduate School of Biostudies, Kyoto University Toshiharu Shikanai Department of Botany, Graduate School of Science, Kyoto University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Photosynthetic electron transfer and its regulation processes take place on thylakoid membranes, and the thylakoid of vascular plants exhibits particularly intricate structure consisting of stacked grana and flat stroma lamellae. It is known that several membrane remodeling proteins contribute to maintain the thylakoid structure, and one putative example is FUZZY ONION LIKE (FZL). In this study, we re-evaluated the controversial function of FZL in thylakoid membrane remodeling and in photosynthesis. We investigated the sub-membrane localization of FZL and found that it is enriched on curved grana edges of thylakoid membranes, consistent with the previously proposed model that FZL mediates fusion of grana and stroma lamellae at the interfaces. The mature fzl thylakoid morphology characterized with the staggered and less connected grana seems to agree with this model as well. In the photosynthetic analysis, the fzl knockout mutants in Arabidopsis displayed reduced electron flow, likely resulting in higher oxidative levels of Photosystem I (PSI) and smaller proton motive force (pmf). However, nonphotochemical quenching (NPQ) of chlorophyll fluorescence was excessively enhanced considering the pmf levels in fzl, and we found that introducing kea3-1 mutation, lowering pH in thylakoid lumen, synergistically reinforced the photosynthetic disorder in the fzl mutant background. We also showed that state transitions normally occurred in fzl, and that they were not involved in the photosynthetic disorders in fzl. We discuss the possible mechanisms by which the altered thylakoid morphology in fzl leads to the photosynthetic modifications. 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.

Public Library of Science Acta Medica Okayama 1932-6203 18 5 2023 Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201 e0285273 EN Hiromasa Yamamoto Department of Thoracic Surgery, Okayama University Hospital Junichi Soh Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine Norihito Okumura Department of Thoracic Surgery, Kurashiki Central Hospital Hiroyuki Suzuki Department of Chest Surgery, Fukushima Medical University Hospital Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School Hospital Toshiya Fujiwara Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital Kenichi Gemba Department of Respiratory Medicine, Chugoku Central Hospital Isao Sano Department of Respiratory Surgery, Japanese Red Cross Nagasaki Genbaku Hospital Takuji Fujinaga Department of General Thoracic Surgery, National Hospital Organization Nagara Medical Center Masafumi Kataoka Department of Surgery and Respiratory Center, Okayama Saiseikai General Hospital Yasuhiro Terazaki Department of Respiratory S0urgery, Saga-Ken Medical Centre Koseikan Nobukazu Fujimoto Department of Medical Oncology and Respiratory Medicine, Okayama Rosai Hospital Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinji Kosaka Department of Thoracic Surgery, Shimane Prefectural Central Hospital Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center Hidetoshi Inokawa Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center Masaaki Inoue Department of Chest Surgery, Shimonoseki City Hospital Hiroshige Nakamura Division of General Thoracic Surgery, Tottori University Hospital Yoshinori Yamashita Department of Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine Keitaro Matsuo Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Junichi Sakamoto Tokai Central Hospital Hiroshi Date Department of Thoracic Surgery, Kyoto University Hospital Shinichi Toyooka Department of Thoracic Surgery, Okayama University Hospital Background<br> It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.<br> <br> Methods<br> Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.<br> <br> Results<br> We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).<br> <br> Conclusion<br> Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 135 2 2023 令和４年度岡山医学会賞　脳神経研究奨励賞（新見賞） 61 62 EN Yuji Yada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-8194 35 9 2023 Neuropeptidergic control circuits in the spinal cord for male sexual behaviour: Oxytocin–gastrin‐releasing peptide systems e13324 EN Takumi Oti Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University The neuropeptidergic mechanisms controlling socio-sexual behaviours consist of complex neuronal circuitry systems in widely distributed areas of the brain and spinal cord. At the organismal level, it is now becoming clear that “hormonal regulations” play an important role, in addition to the activation of neuronal circuits. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” Oxytocin, long known as a neurohypophyseal hormone, is now known to be involved in the regulation of socio-sexual behaviors in mammals, ranging from social bonding to empathy. However, the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system remains unclear. Oxytocin is known to be synthesised mainly in hypothalamic neurons and released from the posterior pituitary into the circulation. Oxytocin is also released from the dendrites of the neurons into the hypothalamus where they have important roles in social behaviours via non-synaptic volume transmission. Because the most familiar functions of oxytocin are to regulate female reproductive functions including parturition, milk ejection, and maternal behaviour, oxytocin is often thought of as a “feminine” hormone. However, there is evidence that a group of parvocellular oxytocin neurons project to the lower spinal cord and control male sexual function in rats. In this report, we review the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system and effects of these neuropeptides on male sexual behaviour. Furthermore, we discuss the finding of a recently identified, localised “volume transmission” role of oxytocin in the spinal cord. Findings from our studies suggest that the newly discovered “oxytocin-mediated spinal control of male sexual function” may be useful in the treatment of erectile and ejaculatory dysfunction. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1364-8535 27 1 2023 Prevalence, reasons, and timing of decisions to withhold/withdraw life-sustaining therapy for out-of-hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation 252 EN Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaaki Sakuraya Department of Emergency and Intensive Care Medicine, JA Hiroshima General Hospital Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroaki Takada Department of Critical Care Medicine and Trauma, National Hospital Organization Disaster Medical Center Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Faculty of Medicine, Dentistry, and Pharmaceutical Science Toru Hifumi Department of Emergency and Critical Care Medicine, St. Luke’s International Hospital Akihiko Inoue Department of Emergency and Critical Care Medicine, Hyogo Emergency Medical Center Tetsuya Sakamoto Department of Emergency Medicine, Teikyo University School of Medicine Yasuhiro Kuroda Department of Emergency, Disaster, and Critical Care Medicine, Faculty of Medicine, Kagawa University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Faculty of Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences SAVE-J II Study Group Background　Extracorporeal cardiopulmonary resuscitation (ECPR) is rapidly becoming a common treatment strategy for patients with refractory cardiac arrest. Despite its benefits, ECPR raises a variety of ethical concerns when the treatment is discontinued. There is little information about the decision to withhold/withdraw life-sustaining therapy (WLST) for out-of-hospital cardiac arrest (OHCA) patients after ECPR.<br> Methods　We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter study of ECPR in Japan. Adult patients who underwent ECPR for OHCA with medical causes were included. The prevalence, reasons, and timing of WLST decisions were recorded. Outcomes of patients with or without WLST decisions were compared. Further, factors associated with WLST decisions were examined.<br> Results　We included 1660 patients in the analysis; 510 (30.7%) had WLST decisions. The number of WLST decisions was the highest on the first day and WSLT decisions were made a median of two days after ICU admission. Reasons for WLST were perceived unfavorable neurological prognosis (300/510 [58.8%]), perceived unfavorable cardiac/pulmonary prognosis (105/510 [20.5%]), inability to maintain extracorporeal cardiopulmonary support (71/510 [13.9%]), complications (10/510 [1.9%]), exacerbation of comorbidity before cardiac arrest (7/510 [1.3%]), and others. Patients with WLST had lower 30-day survival (WLST vs. no-WLST: 36/506 [7.1%] vs. 386/1140 [33.8%], p < 0.001). Primary cerebral disorders as cause of cardiac arrest and higher severity of illness at intensive care unit admission were associated with WLST decisions.<br> ConclusionFor approximately one-third of ECPR/OHCA patients, WLST was decided during admission, mainly because of perceived unfavorable neurological prognoses. Decisions and neurological assessments for ECPR/OHCA patients need further analysis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 3 2023 Associations between Comorbidities and Acute Exacerbation of Interstitial Lung Disease after Primary Lung Cancer Surgery 301 309 EN Takahide Kato Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Seigo Miyoshi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Chizuru Hamada Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Yoshifumi Sano Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine Naoyuki Nogami Department of Community Medicine, Pulmonology and Cardiology, Ehime University Graduate School of Medicine Osamu Yamaguchi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Naohiko Hamaguchi Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Original Article 10.18926/AMO/65495 Acute exacerbation (AE) of interstitial lung disease (ILD) is a severe complication of lung resection in lung cancer patients with ILD (LC-ILD). This study aimed to assess the predictive value of comorbidities other than ILD for postoperative AE in patients with LC-ILD. We retrospectively evaluated 68 patients with LC-ILD who had undergone lung resection. We classified them into two groups: those who had developed postoperative AE within 30 days after resection and those who had not. We analyzed patient characteristics, high-resolution computed tomography findings, clinical data, pulmonary function, and intraoperative data. The incidence of postoperative AEs was 11.8%. In univariate analysis, performance status (PS), honeycombing, forced vital capacity (FVC), and high hemoglobin A1c (HbA1c) levels without comorbidities were significantly associated with postoperative AE. Patients were divided into two groups according to cutoff levels of those four variables as determined by receiver operating characteristic curves, revealing that the rates of patients without postoperative AE differed significantly between groups. The present results suggested that preoperative comorbidities other than ILD were not risk factors for postoperative AE in patients with LC-ILD. However, a high preoperative HbA1c level, poor PS, low FVC, and honeycombing may be associated with postoperative AE of LC-ILD. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 13 1 2023 Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model EN Yifu Lu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroko Shimizu Department of Anesthesiology and Resuscitology, Okayama University Medical School Ryu Nakamura Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Yaqiang Li Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Risa Sakamoto Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Emiko Omori Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Toru Takahashi Okayama Saidaiji Hospital Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Association between depression in chronic phase and future clinical outcome of patients with schizophrenia EN Yuto YAMADA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 The validity of atypical psychosis diagnostic criteria to detect anti-NMDA receptor encephalitis with psychiatric symptoms EN Kenji HINOTSU Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2688-1152 4 2 2023 Association between prehospital advanced life support by emergency medical services personnel and neurological outcomes among adult out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation: A secondary analysis of the SAVE-J II study e12948 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toru Hifumi Department of Emergency and Critical Care Medicine, St. Luke’s International Hospital Akihiko Inoue Department of Emergency, Disaster and Critical Care Medicine, Hyogo Emergency Medical Center Tetsuya Sakamoto Department of Emergency Medicine, Teikyo University School of Medicine Yasuhiro Kuroda Department of Emergency, Disaster, and Critical Care Medicine, Kagawa University Hospital Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University SAVE-J II study group Study Objective: Early deployment of extracorporeal cardiopulmonary resuscitation (ECPR) is critical in treating refractory out-of-hospital cardiac arrest (OHCA) patients who are potential candidates for ECPR. The effect of prehospital advanced life support (ALS), including epinephrine administration or advanced airway, compared with no ALS in this setting remains unclear. This study's objective was to determine the association between any prehospital ALS care and outcomes of patients who received ECPR with emergency medical services-treated OHCA.<br> Methods: This was a secondary analysis of data from the Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J) II study. Patients were separated into 2 groups-those who received prehospital ALS (ALS group) and those did not receive prehospital ALS (no ALS group). Multiple logistic regression analysis was used to investigate the association between prehospital ALS and favorable neurological outcomes (defined as Cerebral Performance Category scores 1-2) at hospital discharge.<br> Results: A total of 1289 patients were included, with 644 patients in the ALS group and 645 patients in the no ALS group. There were fewer favorable neurological outcomes at hospital discharge in the ALS group compared with the no ALS group (10.4 vs 19.8%, p <0.001). A multiple logistic regression analysis revealed that any prehospital ALS care (adjusted odds ratios 0.47; 95% confidence interval 0.34-0.66; p <0.001) was associated with unfavorable neurological outcomes at hospital discharge.<br> Conclusion: Prehospital ALS was associated with worse neurological outcomes at hospital discharge in patients treated with ECPR for OHCA. Further prospective studies are required to determine the clinical implications of these findings. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 2 2023 Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response e0281516 EN Yuki Kyunai Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Mika Sakamoto National Institute of Genetics, ROIS Mayuko Koreishi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshio Tsujino Graduate School of Science, Technology, and Innovation, Kobe University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University GlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidant response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0901-5027 52 4 2023 Relationships between squamous cell carcinoma antigen and cytokeratin 19 fragment values and renal function in oral cancer patients 417 422 EN K. Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences H. Yutori Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences K. Yoshida Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Y. Sakamoto Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences K. Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences S. Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment (CYFRA) are used to screen and monitor oral cancer patients. However, recent studies have reported that tumour markers become elevated as renal function decreases, regardless of tumour progression. A retrospective study was performed of 423 oral cancer patients who underwent blood testing for these tumour markers and other blood analytes during a 10-year period. The values of SCC-Ag and CYFRA increased significantly with decreasing renal function (P < 0.01), and the values were abnormal at a median 2.6 ng/ml for SCC-Ag and 4.7 ng/ml for CYFRA in the group with estimated glomerular filtration rate (eGFR) values of< 30 ml/min/1.73 m2. The factors that were related to the variation in tumour markers were albumin and creatinine. The cut-off values of eGFR were 59.7 ml/min/1.73 m2 for SCC-Ag and 63.6 ml/min/1.73 m2 for CYFRA, and the cut-off age when the tumour markers might rise due to the effect of renal function were 72 years for SCC-Ag and 73 years for CYFRA. In conclusion, decreased renal function should be taken into account when evaluating tumour markers in oral cancer. In addition, tumour markers are likely to be overestimated in patients over the age of 72–73 years. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Locally Advanced Rectal Cancer Invading the Gluteus Maximus Muscle Completely Responded to Total Neoadjuvant Therapy 209 213 EN Masaki Sakamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/65152 A 70-year-old male with anal pain and fever was diagnosed with rectal cancer perforation and abscess in the right gluteus maximus (GM) muscle. He underwent a transverse colon colostomy followed by preoperative capecitabine+oxaliplatin. Some local control was achieved but a residual abscess was observed in the right GM muscle. To secure circumferential resection margin by tumor reduction, he received chemoradiotherapy as total neoadjuvant therapy (TNT) and underwent laparoscopic abdominoperineal resection, D3 lymph node dissection, combined coccyx resection, and partial resection of the right GM muscle. The skin defect and pelvic dead space were filled with a right lateral vastus lateral great muscle flap. Histopathologically, the resected specimen showed no tumor cells in the primary tumor or lymph nodes, indicating a pathological complete response (pCR). This case suggests that TNT might improve the R0 resection and pCR rates and overall survival. 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.

BMC Acta Medica Okayama 1471-2318 23 1 2023 Protocol for a randomised, placebo-controlled, double-blinded clinical trial on the effect of oestrogen replacement on physical performance to muscle resistance exercise for older women with osteoarthritis of knee joint: the EPOK trial 104 EN Tomohiro Mitoma Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Jota Maki Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hikaru Ooba Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Eriko Eto Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Takahashi Department of Obstetrics and Gynecology, Ochiai Hospital Tsunemasa Kondo Department of Obstetrics and Gynecology, Ochiai Hospital Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Yoko Sakamoto Center for Innovative Clinical Medicine, Okayama University Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hisashi Masuyama Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Background:Knee osteoarthritis (KOA) is highly prevalent in older women, and previous studies suggest the involvement of hormonal factors play a role in the pathogenesis of osteoarthritis. KOA causes musculoskeletal impairment, resulting in decreased physical activity, muscle mass, and strength, which leads to sarcopenia and further increases the burden on healthcare systems. Oestrogen replacement therapy (ERT) improves joint pain and muscle performance in early menopausal women. Muscle resistance exercise (MRE) is a non-pharmacological method that preserves the physical functions of patients with KOA. However, data on short-term oestrogen administration combined with MRE in postmenopausal women, especially in those aged > 65 years, are limited. Therefore, this study presents a protocol of a trial aimed to examine the synergistic effect of ERT and MRE on lower-limb physical performance in older women with KOA. Methods:We will conduct a double-blinded, randomised placebo-controlled trial in 80 Japanese women aged > 65 years living independently with knee pain. The participants will be randomly categorised into two groups: (1) 12-week MRE programme with transdermal oestrogen gel containing 0.54 mg oestradiol per push and (2) 12-week MRE programme with placebo gel. The primary outcome measured using the 30-s chair stand test, and secondary outcomes (body composition, lower-limb muscle strength, physical performance, self-reported measure of knee pain, and quality of life) will be measured at baseline, 3 months, and 12 months, and these outcomes will be analysed based on the intention-to-treat. Discussion:The EPOK trial is the first study to focus on the efficacy of ERT on MRE among women aged > 65 years with KOA. This trial will provide an effective MRE to prevent KOA-induced lower-limb muscle weakness, confirming the benefit of short-term oestrogen administration. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 2470-1343 8 2023 Detection of Membrane Potential-Dependent Rhodopsin Fluorescence Using Low-Intensity Light Emitting Diode for Long-Term Imaging 4826 4834 EN Shiho Kawanishi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichi Kojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Shibukawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayuki Sakamoto Department of Optical Neural and Molecular Physiology, Graduate School of Biostudies Yuki Sudo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Faculty of Medicine, Dentistry and Pharmaceutical Sciences Microbial rhodopsin is a family of photoreceptive membrane proteins that commonly consist of a seven-transmembrane domain and a derivative of vitamin-A, retinal, as a chromophore. In 2011, archaeorhodopsin-3 (AR3) was shown to exhibit voltage-dependent fluorescence changes in mammalian cells. Since then, AR3 and its variants have been used as genetically encoded voltage indicators, in which mostly intense laser stimulation (1-1000 W/cm(2)) is used for the detection of dim fluorescence of rhodopsin, leading to high spatiotemporal resolution. However, intense laser stimulation potentially causes serious cell damage, particularly during long-term imaging over minutes. In this study, we present the successful detection of voltage-sensitive fluorescence of AR3 and its high fluorescence mutant Archon1 in a variety of mammalian cell lines using low-intensity light emitting diode stimulation (0.15 W/cm2) with long exposure time (500 ms). The detection system enables real-time imaging of drug-induced slow changes in voltage within the cells for minutes harmlessly and without fluorescence bleaching. Therefore, we demonstrate a method to quantitatively understand the dynamics of slow changes in membrane voltage on long time scales. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 17 12 2022 Behavioural osmoregulation during land invasion in fish: Prandial drinking and wetting of the dry skin e0277968 EN Yukitoshi Katayama Ushimado Marine Institute, Faculty of Science, Okayama University Takehiro Tsukada Department of Biomolecular Science, Toho University Susumu Hyodo Laboratory of Physiology, Atmosphere and Ocean Research Institute, University of Tokyo Hirotaka Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Osmoregulatory behaviours should have evolutionarily modified for terrestrialisation of vertebrates. In mammals, sensations of buccal food and drying have immediate effects on postprandial thirst to prevent future systemic dehydration, and is thereby considered to be 'anticipatory thirst'. However, it remains unclear whether such an anticipatory response has been acquired in the non-tetrapod lineage. Using the mudskipper goby (Periophthalmus modestus) as a semi-terrestrial ray-finned fish, we herein investigated postprandial drinking and other unique features like full-body 'rolling' over on the back although these behaviours had not been considered to have osmoregulatory functions. In our observations on tidal flats, mudskippers migrated into water areas within a minute after terrestrial eating, and exhibited rolling behaviour with accompanying pectoral-fin movements. In aquarium experiments, frequency of migration into a water area for drinking increased within a few minutes after eating onset, without systemic dehydration. During their low humidity exposure, frequency of the rolling behaviour and pectoral-fin movements increased by more than five times to moisten the skin before systemic dehydration. These findings suggest anticipatory responses which arise from oral/gastrointestinal and cutaneous sensation in the goby. These sensation and motivation seem to have evolved in distantly related species in order to solve osmoregulatory challenges during terrestrialisation. 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.

MDPI Acta Medica Okayama 1660-4601 20 2 2023 Differences in Stress Perception of Medical Students Depending on In-Person Communication and Online Communication during the COVID-19 Pandemic: A Japanese Cross-Sectional Survey 1579 EN Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Nishimura Department of Medicine, John A. Burns School of Medicine, University of Hawai’i Yoko Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Mikako Obika 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 Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Excessive psychological stress in medical students affects their mental health and causes problems such as burnout and depression. Furthermore, changes in the learning environment to online learning due to the COVID-19 pandemic have had a psychological effect on medical students. However, the relationships between medical students' perceived stress and different methods of communication, including in-person and online communication, remain unclear. The purpose of this study was to investigate the differences in stress perception of medical students depending on in-person communication and online communication during the COVID-19 pandemic. Methods: This study was a cross-sectional study conducted from September to October in 2020. All of the students of Okayama University School of Medicine were asked to participate in a questionnaire survey. The explanatory variables were the frequency and length of communications with others (by in-person or online communication), empathy, and lifestyle. The main outcome measure was perceived stress. Subgroup analysis was conducted for students who preferred to be by themselves and students who preferred to study together and interact with other people. Univariate analysis and multivariate multiple regression analysis were conducted. Gender and grade, which have been shown to be associated with stress in previous studies, were used as covariates for multiple regression analysis. Results: Valid responses to the questionnaire survey were received from 211 (29.4%) of the 717 students. There was no significant association between perceived stress and online communication, but the number of people with which students had in-person communication (1-2 people compared to 0 as a control, regression coefficient [B] = -4.4, 95% confidence interval [CI]; -7.8, -1.1, more than 10 people, B = -12, 95% CI: -18, -5.8) and the length of communication (more than 120 min, B = -4.5, 95% CI: -8.1, -0.92) were associated with a reduction in perceived stress. In subgroup analysis, the number of people with in-person communication and the length of communication had significant associations with stress reduction even in the group of students who had a preference for being by themselves. Conclusion: In-person communications rather than online communications were associated with a lower level of perceived stress. In subgroup analysis, this trend was statistically significant in the group of students who had a preference for being by themselves. No potential conflict of interest relevant to this article was reported.

Taylor & Francis Ltd Acta Medica Okayama 1742-9145 18 1 2023 Identification of quantitative trait loci associated with sorghum susceptibility to Asian stem borer damage 2153182 EN Cyprian Osinde Institute of Plant Science and Resources, Okayama University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Hiromi Kajiya-Kanegae Graduate School of Agricultural and Life Sciences, The University of Tokyo Islam S. Sobhy Institute of Plant Science and Resources, Okayama University Arthur K. Tugume Department of Plant Science, Microbiology and Biotechnology Makerere University Anthony M. Nsubuga Department of Plant Science, Microbiology and Biotechnology Makerere University Ivan Galis Institute of Plant Science and Resources, Okayama University Sorghum (Sorghum bicolor (L.) Moench) is an important crop originated in Africa that shows susceptibility to herbivores. In this study, we identified two sorghum genotypes with highly contrasting levels of stem damage caused by the caterpillars of Asian stem borer (Ostrinia furnacalis Guenee). Recombinant inbred lines (RILs) from genetic cross between resistant (BTx623) and susceptible (NOG) sorghum were used to perform a quantitative trait locus (QTL) analysis in the field. Two major QTLs responsible for higher NOG infestation by stem borer in three independent field seasons were detected on chromosomes 7 and 9, interestingly in positions that overlapped with two major QTLs for plant height. As plant height and stem borer damage were highly correlated, we propose that sorghum height-associated morphological or physiological traits could be important for stem borer establishment and/or damage in sorghum. No potential conflict of interest relevant to this article was reported.

岡山大学文明動態学研究所 Acta Medica Okayama 2436-8326 2 2023 岡山大学構内遺跡における水田稲作の開始年代 ―�T期中段階の堰の酸素同位体比年輪年代と炭素14年代― 18 31 EN Shinichiro FUJIO The National Museum of Japanese History, School of Cultural and Social Studies, The Graduate University for Advanced Studies Minoru SAKAMOTO The National Museum of Japanese History, School of Cultural and Social Studies, The Graduate University for Advanced Studies Masaki SANO Graduate School of Environmental Studies, Nagoya University 研究ノート (Research note) 10.18926/64199 This article clarifies the date when paddy field rice cultivation began at the archaeological site located within the Okayama University campus. The analysis used tree ring oxygen isotope dating and radiocarbon dating. When the oxygen isotope ratios of wood used in paddy weirs detected in the 23rd excavation season were examined, peaks could be seen in two places: in the 10th century BC and the 6th century BC. Since the weir was accompanied by mid-I stage Yayoi pottery, which was dated to the 6th century BC using radiocarbon dating, tree ring dating determined that the weir was made from wood cut down soon after 540 BC. Therefore, it was reaffirmed that one of the points of the mid-I stage can be dated to the middle of the 6th century BC. <br> Next is the age of the early-I stage, when paddy field rice cultivation began on the Okayama Plain. In the Tsuruba area of the Nishikawazu archaeological site in Shimane Prefecture, where paddy field rice cultivation is thought to have begun at the same time as on the Okayama Plain, tree ring oxygen isotope dating of wood accompanied by early-I stage pottery has been reported. The date of 649 BC date means that one of the earliest stages of the early-I period dates to the middle of the 7th century BC. Therefore, we reaffirmed the view that paddy rice cultivation in the Chugoku region, such as Okayama and Shimane, began in the 7th century BC. <br> It also became clear that the beginning of paddy field rice cultivation in the Chugoku region occurred at a time when the climate that had been the base of cold in the 10th century BC gradually warmed and the relatively humid climate began to turn to arid. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 12 1 2022 Mating experiences with the same partner enhanced mating activities of naive male medaka fish 19665 EN Masahiro Daimon Graduate School of Natural Science and Technology, Okayama University Takafumi Katsumura Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Graduate School of Natural Science and Technology, Okayama University Satoshi Ansai Graduate School of Life Sciences, Tohoku University Hideaki Takeuchi Graduate School of Natural Science and Technology, Okayama University Mating experience shapes male mating behavior across species, from insects, fish, and birds, to rodents. Here, we investigated the effect of multiple mating experiences on male mating behavior in "naive" (defined as sexually inexperienced) male medaka fish. The latency to mate with the same female partner significantly decreased after the second encounter, whereas when the partner was changed, the latency to mate was not decreased. These findings suggest that mating experiences enhanced the mating activity of naive males for the familiar female, but not for an unfamiliar female. In contrast, the mating experiences of "experienced" (defined as those having mated > 7 times) males with the same partner did not influence their latency to mate. Furthermore, we identified 10 highly and differentially expressed genes in the brains of the naive males after the mating experience and revealed 3 genes that are required for a functional cascade of the thyroid hormone system. Together, these findings suggest that the mating experience of naive male medaka fish influences their mating behaviors, with neural changes triggered by thyroid hormone activation in the brain. No potential conflict of interest relevant to this article was reported.

The Royal Society Acta Medica Okayama 0962-8452 289 1985 2022 Footedness for scratching itchy eyes in rodents 20221126 EN Yukitoshi Katayama Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi Ayane Miura Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi Keiko Takanami Mouse Genomics Resources Laboratory, National Institute of Genetics, Yata, Mishima Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi The neural bases of itchy eye transmission remain unclear compared with those involved in body itch. Here, we show in rodents that the gastrin-releasing peptide receptor (GRPR) of the trigeminal sensory system is involved in the transmission of itchy eyes. Interestingly, we further demonstrate a difference in scratching behaviour between the left and right hindfeet in rodents; histamine instillation into the conjunctival sac of both eyes revealed right-foot biased laterality in the scratching movements. Unilateral histamine instillation specifically induced neural activation in the ipsilateral sensory pathway, with no significant difference between the activations following left- and right-eye instillations. Thus, the behavioural laterality is presumably due to right-foot preference in rodents. Genetically modified rats with specific depletion of Grpr-expressing neurons in the trigeminal sensory nucleus caudalis of the medulla oblongata exhibited fewer and shorter histamine-induced scratching movements than controls and eliminated the footedness. These results taken together indicate that the Grp-expressing neurons are required for the transmission of itch sensation from the eyes, but that foot preference is generated centrally. These findings could open up a new field of research on the mechanisms of the laterality in vertebrates and also offer new potential therapeutic approaches to refractory pruritic eye disorders. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Salvage Surgery for Symptomatic Recurrence of Retro-Odontoid Pseudotumor after a C1 Laminectomy 749 754 EN Masanari Takami Department of Orthopaedic Surgery, Wakayama Medical University Yasutsugu Yukawa Department of Orthopaedic Surgery, Wakayama Medical University Yusuke Noda Department of Orthopaedic Surgery, Wakayama Rosai Hospital Munehito Yoshida Department of Orthopaedic Surgery, Wakayama Medical University Hiroshi Yamada Department of Orthopaedic Surgery, Wakayama Medical University Case Report 10.18926/AMO/64127 We provide the first report of successful salvage surgery for a post-C1 laminectomy symptomatic recurrence of a retro-odontoid pseudotumor (ROP) that caused myelopathy. The 72-year-old Japanese woman presented with an ROP causing symptomatic cervical myelopathy. With ultrasonography support, we performed the enucleation of the ROP via a transdural approach and fusion surgery for the recurrence of the mass. At the final observation 2-year post-surgery, MRI demonstrated the mass’s regression and spinal cord decompression, and the patient’s symptoms had improved. Our strategy is an effective option for a symptomatic recurrence of ROP. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Posterolateral Floating Technique for the Thoracic Ossification of the Posterior Longitudinal Ligament with Navigation: A Technical Note 743 748 EN Masato Tanaka Department of Orthopaedic Surgery, Okayama Rosai Hospital Hardik Suthar Department of Orthopaedic Surgery, Okayama Rosai Hospital Dhvanit Desai Department of Orthopaedic Surgery, Okayama Rosai Hospital Taro Yamauchi Department of Orthopaedic Surgery, Okayama Rosai Hospital Shinya Arataki 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 Yoshiaki Oda Department of Orthopaedic Surgery, Okayama Rosai Hospital Haruo Misawa Department of Orthopaedic Surgery, Okayama University Hospital Case Report 10.18926/AMO/64126 We describe a floating technique via a posterolateral approach with intraoperative O-arm navigation to facilitate decompression of the spinal cord in thoracic myelopathy due to severe ossification of the posterior longitudinal ligament (OPLL). A 62-year-old man with myelopathy due to thoracic OPLL had left-leg muscle weakness, urinary disturbance, and spastic gait. Bilateral leg pain and gait disturbance had persisted for 2 years. He was successfully treated by the posterolateral OPLL floating procedure and posterior pedicle fixation under O-arm navigation. At a 2-year follow-up, manual muscle testing results and sensory function of the left leg had recovered fully. His cervical Japanese Orthopedic Association score had improved from 5/12 to 11/12. The novel intraoperative O-arm navigation-guided posterolateral floating procedure for thoracic OPLL is effective for achieving precise decompression and strong fixation with a posterior approach only and can provide an excellent result for severe thoracic OPLL without the risk of adverse events from intraoperative radiation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Graphene Oxide-based Endodontic Sealer: An in Vitro Study 715 721 EN Mohammed Zahedul Islam Nizami Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Melahat Gorduysus Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Shinoda-Ito Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Shogo Takashiba Research Core for Interdisciplinary Sciences, Okayama University Zulema Arias Department of Pathophysiology – Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/64122 The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall. 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 Efficacy and Safety of Three-dimensional Conformal Radiotherapy for Macroscopic Vascular Invasion of Hepatocellular Carcinoma 679 688 EN Akinori Asagi Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center Chihiro Sakaguchi Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center Seijin Nadano Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center Tomohiro Nishina Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center Yasushi Hamamoto Department of Radiation Oncology, National Hospital Organization Shikoku Cancer Center Masaaki Kataoka Department of Radiology, Saiseikai Imabari Hospital Natsumi Yamashita Department of Clinical Research Center, National Hospital Organization Shikoku Cancer Center Masahito Tanimizu Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center Ichinosuke Hyodo Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center Original Article 10.18926/AMO/64118 Chemotherapy is insufficient to treat macroscopic vascular invasion (MVI) of hepatocellular carcinoma (HCC). We retrospectively investigated the treatment outcomes of patients who underwent three-dimensional conformal radiotherapy (3D-CRT) for HCC MVI and analyzed prognostic factors by multivariate analysis using a Cox proportional hazard model. Sixty-five patients were studied. MVI sites were the portal vein (n=48 patients), portal and hepatic veins (n=8), and hepatic vein (n=9). The median irradiation dose was 50 Gy. The median survival time (MST) was 7.5 months. Performance status 2 or 3, modified albumin-bilirubin grade 2b or 3, and massive/diffuse type were poor prognostic factors. Nineteen patients (29%) with a treatment effect of 3 or 4 (≥ 50% of tumor necrosis or regression) at the irradiation sites according to the Response Evaluation Criteria in Cancer of the Liver showed longer survival than those with an effect of 1 or 2 (MST 18.7 vs. 5.9 months, p<0.001). No treatment-related death occurred. The hepatic function reserve was preserved in more than 70% of patients. 3D-CRT controlled HCC MVI safely and was suggested to be a good treatment option. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Clinical moderators of response to nalmefene in a randomized-controlled trial for alcohol dependence: An exploratory analysis EN Nozomu HASHIMOTO 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 76 5 2022 Idiopathic Pneumonia Syndrome Refractory to Ruxolitinib after Post-Transplant Cyclophosphamide-based Haploidentical Hematopoietic Stem Cell Transplantation: Lung Pathological Findings from an Autopsy Case 609 615 EN Ken Matsumoto Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Keigo Fujishita Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Masayuki Matsuda Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuka Fujisawa Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Takuya Machida Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Case Report 10.18926/AMO/64044 A 69-year-old Japanese man with acute leukemia received post-transplant cyclophosphamide-based haploidentical stem cell transplantation (PTCY-haplo-SCT) but was readmitted with dyspnea and ground-glass-opacities of the lungs. Bronchoscopy showed inflammatory changes with no signs of infection. He received steroids but required intubation as his condition deteriorated. In addition to antithymocyte globulin and cyclophosphamide, we administered ruxolitinib but failed to save him. Autopsy findings revealed fibrotic nonspecific interstitial pneumonia (NSIP) without evidence of organizing pneumonia or infection. Thus, we diagnosed idiopathic pneumonia syndrome (IPS). As far as our knowledge, this is the first case of IPS with NSIP histology after PTCY-haplo-SCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Surgery Outcomes for Pulmonary Metastases from Renal Cell Carcinoma 585 591 EN Haruki Choshi Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Mototsugu Watanabe Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Shinichi Furukawa Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Hiroyuki Ujike Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Kazuhiko Kataoka Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center Original Article 10.18926/AMO/64040 Pulmonary metastatic resection is a standard therapy for renal cell carcinoma (RCC). Although patients with pulmonary metastases who do not undergo any treatment have poor prognoses, it has been reported that resection for pulmonary metastases yields good clinical outcomes. We investigated the prognoses of the 10 Japanese patients (eight males, two females) who underwent a surgical resection of pulmonary metastasectomy from RCC at our institution between April 1, 2012 and March 31, 2020 and analyzed the prognostic factors. We determined the prognoses and calculated the 5-year overall survival (OS) and disease-free survival (DFS) rates. To identify prognostic factors, we compared the median DFS duration for each factor. Elderly patients (median age, 75.5 years) were more predominant compared to previous studies, and all 10 patients underwent a complete resection. The 5-year DFS rate was 30.5% (95%CI: 0.045-0.63) and the 5-year OS rate was 80% (95%CI: 0.20-0.97). The following factors were associated with better prognosis: female, disease-free interval≥36 months, and metastases size<12 mm. These results indicate that complete resection for pulmonary metastases from RCC resulted in good clinical outcomes, particularly for patients with better prognostic factors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Effects of Model-Based Iterative Reconstruction in Low-Dose Paranasal Computed Tomography: A Comparison with Filtered Back Projection and Hybrid Iterative Reconstruction 511 517 EN Hayato Tomita Department of Radiology, St. Marianna University School of Medicine Kenji Kuramochi Department of Radiology, St. Marianna University School of Medicine Atsuko Fujikawa Department of Radiology, St. Marianna University School of Medicine Hirotaka Ikeda Department of Radiology, Fujita Health University School of Medicine Midori Komita Department of Radiology, St. Marianna University School of Medicine Yoshiko Kurihara Department of Radiology, Machida Municipal Hospital Yasuyuki Kobayashi Department of Advanced Biomedical Imaging Informatics, St. Marianna University School of Medicine Hidefumi Mimura Department of Radiology, St. Marianna University School of Medicine Original Article 10.18926/AMO/64031 Iterative reconstruction (IR) improves image quality compared with filtered back projection (FBP). This study investigated the usefulness of model-based IR (forward-projected model-based iterative reconstruction solution [FIRST]) in comparison with FBP and hybrid IR (adaptive iterative dose reduction three-dimensional processing [AIDR 3D]) in low-dose paranasal CT. Twenty-four patients with paranasal sinusitis who underwent standard-dose CT (120 kV) and low-dose CT (100 kV) scanning before and after medical treatment were enrolled. Standard-dose CT scans were reconstructed with FBP (FBP120), and low-dose CT scans with FBP (FBP100), AIDR 3D, and FIRST. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in three anatomical structures and effective doses were compared using Mann–Whitney U test. Two radiologists independently evaluated the visibility of 16 anatomical structures, overall image quality, and artifacts. Effective doses in lowdose CT were significantly reduced compared with those in standard-dose CT (0.24 vs 0.43 mSv, p<0.001). FIRST achieved significantly higher SNR (p<0.01, respectively) and CNR (p<0.001, respectively) of evaluated structures and significant improvement in overall image quality (p<0.001), artifacts (p<0.001), and visibility related to muscles (p<0.05) compared to FBP120, FBP100, and AIDR 3D. FIRST allowed radiation-dose reduction, while maintaining objective and subjective image quality in low-dose paranasal CT. No potential conflict of interest relevant to this article was reported.

CELL PRESS Acta Medica Okayama 2589-0042 25 7 2022 Lattice-patterned collagen fibers and their dynamics in axolotl skin regeneration 104524 EN Rena Kashimoto Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Saya Furukawa Department of Biological Sciences, Faculty of Science, Okayama University Sakiya Yamamoto Department of Biological Sciences, Faculty of Science, Okayama University Yasuhiro Kamei National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences Joe Sakamoto National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences Shigenori Nonaka National Institute for Basic Biology (NIBB), National Institutes for Natural Sciences Tomonobu M. Watanabe Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR) Tatsuya Sakamoto Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and Technology, Okayama University Akira Satoh Research Core for Interdisciplinary Sciences (RCIS), Okayama University The morphology of collagen-producing cells and the structure of produced collagen in the dermis have not been well-described. This lack of insights has been a serious obstacle in the evaluation of skin regeneration. We succeeded in visualizing collagen-producing cells and produced collagen using the axolotl skin, which is highly transparent. The visualized dermal collagen had a lattice-like structure. The collagen-producing fibroblasts consistently possessed the lattice-patterned filopodia along with the lattice-patterned collagen network. The dynamics of this lattice-like structure were also verified in the skin regeneration process of axolotls, and it was found that the correct lattice-like structure was not reorganized after simple skin wounding but was reorganized in the presence of nerves. These findings are not only fundamental insights in dermatology but also valuable insights into the mechanism of skin regeneration. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 The Impact of Medical Students Teaching Basic Life Support to Laypersons 265 271 EN Yoshinori Kosaki 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 Atsuyoshi Iida Department of Emergency Medicine, Japanese Red Cross Okayama Hospital Hiromi Ihoriya Department of General Medicine, Okayama University Hospital Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Taihei Yamada Department of Emergency, Critical Care, and Disaster Medicine, 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 Shunsuke Nakamura Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuhiro Mandai Department of Emergency Medicine, The JIKEI University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Original Article 10.18926/AMO/63720 Basic life support (BLS) courses for laypersons, including cardiopulmonary resuscitation (CPR) training, is known to improve outcomes of out-of-hospital cardiac events. We asked medical students to provide BLS training for laypersons as a part of their emergency medicine education and evaluated the effects of training on the BLS skills of laypersons. We also used a questionnaire to determine whether the medical students who provided the BLS training were themselves more confident and motivated to perform BLS compared to students who did not provide BLS training. The proportions of laypersons who reported confidence in checking for a response, performing chest compressions, and automated external defibrillator (AED) use were significantly increased after the BLS training. The proportions of medical students who reported increased confidence/motivation in terms of understanding BLS, checking for a response, chest compression, use of AED, and willingness to perform BLS were significantly greater among medical students who provided BLS instructions compared to those who did not. BLS instruction by medical students was associated with an improvement in laypersons’ CPR accuracy and confidence in responding to cardiac arrest. The results indicate that medical students could gain understanding, confidence, and motivation in regard to their BLS skills by teaching BLS to laypersons. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats 255 263 EN Kosuke Nakatsuka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshikazu Matsuoka Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masako Kurita Kinoshita Pain Clinic Ruilin Wang Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chika Tsuboi Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobutaka Sue Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuji Kaku 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/63719 Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Analysis of Immunity against Measles, Mumps, Rubella, and Varicella Zoster in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience 247 253 EN Shohei Yoshida 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 Chihiro Kamoi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wataru Kitamura Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko 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 Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63718 Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2022 Inflammation of the adipose tissue in the retroperitoneal cavity adjacent to pelvic endometriosis EN Kotaro Kubo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0781 63 5 2022 Sorghum Ionomics Reveals the Functional SbHMA3a Allele that Limits Excess Cadmium Accumulation in Grains 713 728 EN Fiona Wacera Wahinya Institute of Plant Science and Resources, Okayama University, Kiyoshi Yamazaki Graduate School of Agricultural and Life Sciences, The University of Tokyo Zihuan Jing Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Takehiro Kamiya Graduate School of Agricultural and Life Sciences, The University of Tokyo Hiromi Kajiya-Kanegae Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization Hideki Takanashi Graduate School of Agricultural and Life Sciences, The University of Tokyo Hiroyoshi Iwata Graduate School of Agricultural and Life Sciences, The University of Tokyo Nobuhiro Tsutsumi Graduate School of Agricultural and Life Sciences, The University of Tokyo Toru Fujiwara Graduate School of Agricultural and Life Sciences, The University of Tokyo Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Understanding uptake and redistribution of essential minerals or sequestering of toxic elements is important for optimized crop production. Although the mechanisms controlling mineral transport have been elucidated in rice and other species, little is understood in sorghum―an important C4 cereal crop. Here, we assessed the genetic factors that govern grain ionome profiles in sorghum using recombinant inbred lines (RILs) derived from a cross between BTx623 and NOG (Takakibi). Pairwise correlation and clustering analysis of 22 elements, measured in sorghum grains harvested under greenhouse conditions, indicated that the parental lines, as well as the RILs, show different ionomes. In particular, BTx623 accumulated significantly higher levels of cadmium (Cd) than NOG, because of differential root-to-shoot translocation factors between the two lines. Quantitative trait locus (QTL) analysis revealed a prominent QTL for grain Cd concentration on chromosome 2. Detailed analysis identified SbHMA3a, encoding a P1B-type ATPase heavy metal transporter, as responsible for low Cd accumulation in grains; the NOG allele encoded a functional HMA3 transporter (SbHMA3a-NOG) whose Cd-transporting activity was confirmed by heterologous expression in yeast. BTx623 possessed a truncated, loss-of-function SbHMA3a allele. The functionality of SbHMA3a in NOG was confirmed by Cd concentrations of F2 grains derived from the reciprocal cross, in which the NOG allele behaved in a dominant manner. We concluded that SbHMA3a-NOG is a Cd transporter that sequesters excess Cd in root tissues, as shown in other HMA3s. Our findings will facilitate the isolation of breeding cultivars with low Cd in grains or in exploiting high-Cd cultivars for phytoremediation. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science (AAAS) Acta Medica Okayama 2375-2548 8 9 2022 Vasopressin-oxytocin–type signaling is ancient and has a conserved water homeostasis role in euryhaline marine planarians eabk0331 EN Aoshi Kobayashi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Mayuko Hamada Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Masa-aki Yoshida Oki Marine Biological Station, Shimane University Yasuhisa Kobayashi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Naoaki Tsutsui Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Toshio Sekiguchi Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University Yuta Matsukawa Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Sho Maejima Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Joseph J. Gingell Vertex Pharmaceuticals (Europe) Ltd. Shoko Sekiguchi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Ayumu Hamamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Debbie L. Hay School of Biological Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland John F. Morris Department of Physiology, Anatomy, and Genetic, Le Gros Clark Building, University of Oxford Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado Vasopressin/oxytocin (VP/OT)–related peptides are essential for mammalian antidiuresis, sociosexual behavior, and reproduction. However, the evolutionary origin of this peptide system is still uncertain. Here, we identify orthologous genes to those for VP/OT in Platyhelminthes, intertidal planarians that have a simple bilaterian body structure but lack a coelom and body-fluid circulatory system. We report a comprehensive characterization of the neuropeptide derived from this VP/OT-type gene, identifying its functional receptor, and name it the “platytocin” system. Our experiments with these euryhaline planarians, living where environmental salinities fluctuate due to evaporation and rainfall, suggest that platytocin functions as an “antidiuretic hormone” and also organizes diverse actions including reproduction and chemosensory-associated behavior. We propose that bilaterians acquired physiological adaptations to amphibious lives by such regulation of the body fluids. This neuropeptide-secreting system clearly became indispensable for life even without the development of a vascular circulatory system or relevant synapses. 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.

Oxford University Press (OUP) Acta Medica Okayama 1574-6968 369 1 2022 Heterogeneous IgE reactivities to Staphylococcus pseudintermedius strains in dogs with atopic dermatitis, and the identification of DM13-domain-containing protein as a bacterial IgE-reactive molecule fnac019 EN Iyo Takemura-Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Tsurui School of Veterinary Medicine, Azabu University, Fuchinobe 1-17-71 Hidekatsu Shimakura School of Veterinary Medicine, Azabu University Tadahiro Nasukawa School of Veterinary Medicine, Azabu University Ichiro Imanishi School of Veterinary Medicine, Azabu University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama Universty Tomoki Fukuyama School of Veterinary Medicine, Azabu University Shuji Sakamoto Science Research Center, Kochi Medical School Keiko Morisawa Science Research Center, Kochi Medical School Masato Fujimura Fujimura Animal Hospital Hironobu Murakami School of Veterinary Medicine, Azabu University Shuji Kanamaru Department of Life Science and Technology, Tokyo Institute of Technology Kenji Kurokawa Faculty of Pharmaceutical Sciences, Nagasaki International University Keiko Kawamoto School of Veterinary Medicine, Azabu University Keita Iyori Vet Derm Tokyo, Dermatological and Laboratory Service for Animals Masahiro Sakaguchi School of Veterinary Medicine, Azabu University <i>Staphylococcus pseudintermedius</i> is one of the major pathogens causing canine skin infection. In canine atopic dermatitis (AD), heterogeneous strains of S. pseudintermedius reside on the affected skin site. Because an increase in specific IgE to this bacterium has been reported, S. pseudintermedius is likely to exacerbate the severity of canine AD. In this study, the IgE reactivities to various S. pseudintermedius strains and the IgE-reactive molecules of S. pseudintermedius were investigated. First, examining the IgE reactivities to eight strains of S. pseudintermedius using 141 sera of AD dogs, strain variation of S. pseudintermedius showed 10–63% of the IgE reactivities. This is different from the expected result based on the concept of Staphylococcus aureus clonality in AD patients. Moreover, according to the western blot analysis, there were more than four proteins reactive to IgE. Subsequently, the analysis of the common IgE-reactive protein at ∼15 kDa confirmed that the DM13-domain-containing protein was reactive in AD dogs, which is not coincident with any S. aureus IgE-reactive molecules. Considering these, S. pseudintermedius is likely to exacerbate AD severity in dogs, slightly different from the case of S. aureus in human AD. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 19 2021 Sexual Experience Induces the Expression of Gastrin-Releasing Peptide and Oxytocin Receptors in the Spinal Ejaculation Generator in Rats 10362 EN Takumi Oti Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Ryota Ueda Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Ryoko Kumagai Department of Animal Sciences, Teikyo University of Science Junta Nagafuchi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Takashi Ito Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Yasuhiko Kondo Department of Animal Sciences, Teikyo University of Science Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Male sexual function in mammals is controlled by the brain neural circuits and the spinal cord centers located in the lamina X of the lumbar spinal cord (L3-L4). Recently, we reported that hypothalamic oxytocin neurons project to the lumbar spinal cord to activate the neurons located in the dorsal lamina X of the lumbar spinal cord (dXL) via oxytocin receptors, thereby facilitating male sexual activity. Sexual experiences can influence male sexual activity in rats. However, how this experience affects the brain-spinal cord neural circuits underlying male sexual activity remains unknown. Focusing on dXL neurons that are innervated by hypothalamic oxytocinergic neurons controlling male sexual function, we examined whether sexual experience affects such neural circuits. We found that >50% of dXL neurons were activated in the first ejaculation group and similar to 30% in the control and intromission groups in sexually naive males. In contrast, in sexually experienced males, similar to 50% of dXL neurons were activated in both the intromission and ejaculation groups, compared to similar to 30% in the control group. Furthermore, sexual experience induced expressions of gastrin-releasing peptide and oxytocin receptors in the lumbar spinal cord. This is the first demonstration of the effects of sexual experience on molecular expressions in the neural circuits controlling male sexual activity in the spinal cord. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Lumbar Artery Injury Related to Percutaneous Pedicle Screw Insertion 85 88 EN Hirotsugu Omi Omi Orthopaedic Clinic Takashi Tomita Department of Orthopaedic Surgery, Aomori Prefectural Central Hospital Masayuki Ichinohe Department of Orthopaedic Surgery, Aomori Prefectural Central Hospital Yoshifumi Harada Department of Orthopaedic Surgery, Aomori Prefectural Central Hospital Hideki Sato Department of Orthopaedic Surgery, Aomori Prefectural Central Hospital Junji Ito Department of Orthopaedic Surgery, Aomori Prefectural Central Hospital Case Report 10.18926/AMO/63216 A 75-year-old woman underwent L4-L5 lateral interbody fusion for L4-5 foraminal stenosis with the use of percutaneous pedicle screws. On the day after the surgery, she was in shock. Emergency contrast-enhanced CT showed active extravasation from the 4th lumbar artery with a transverse process fracture. A radiologist performed a successful transarterial embolization, and the patient then began walking training on the 4th day post-surgery. Close attention should be paid to the insertion of a percutaneous pedicle screw, as it may cause a lumbar artery injury; in such a case, transarterial embolization is the preferred treatment. No potential conflict of interest relevant to this article was reported.

Zoological Society of Japan Acta Medica Okayama 0289-0003 39 1 2022 Observing Phylum-Level Metazoan Diversity by Environmental DNA Analysis at the Ushimado Area in the Seto Inland Sea 157 165 EN Takeshi Kawashima National Institute of Genetics Masa-aki Yoshida Marine Biological Science Section, Education and Research Center Biological Resources, Faculty of Life and Environmental Science, Shimane University Hideyuki Miyazawa National Institute of Genetics Hiroaki Nakano Shimoda Marine Research Center, University of Tsukuba Natumi Nakano Department of Biology, Nara Medical University Tatsuya Sakamoto Ushimado Marine Institute, Okayama University Mayuko Hamada Ushimado Marine Institute, Okayama University The dynamics of microscopic marine plankton in coastal areas is a fundamental theme in marine biodiversity research, but studies have been limited because the only available methodology was collection of plankton using plankton-nets and microscopic observation. In recent years, environmental DNA (eDNA) analysis has exhibited potential for conducting comprehensive surveys of marine plankton diversity in water at fixed points and depths in the ocean. However, few studies have examined how eDNA analysis reflects the actual distribution and dynamics of organisms in the field, and further investigation is needed to determine whether it can detect distinct differences in plankton density in the field. To address this, we analyzed eDNA in seawater samples collected at 1 km intervals at three depths over a linear distance of approximately 3.0 km in the Seto Inland Sea. The survey area included a location with a high density of Acoela (Praesagittifera naikaiensis). However, the eDNA signal for this was little to none, and its presence would not have been noticed if we did not have this information beforehand. Meanwhile, eDNA analysis enabled us to confirm the presence of a species of Placozoa that was previously undiscovered in the area. In summary, our results suggest that the number of sequence reads generated from eDNA samples in our project was not sufficient to predict the density of a particular species. However, eDNA can be useful for detecting organisms that have been overlooked using other methods. No potential conflict of interest relevant to this article was reported.

WILEY Acta Medica Okayama 2045-7634 2021 00 2021 PD-L1 expression is associated with the spontaneous regression of patients with methotrexate-associated lymphoproliferative disorders 1 EN Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Misato Doi Division of Clinical Laboratory, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Misa Sakamoto Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuria Egusa Division of Pathophysiology, Okayama University Graduate School of Health Sciences Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Azusa Fujita Division of Pathophysiology, Okayama University Graduate School of Health Sciences Noriko Iwaki Department of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University Naoya Nakamura Department of Pathology, Tokai University School of Medicine Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Background Most patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) show diffuse large B-cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX-LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL-type MTX-LPD. In this study, we examined whether programmed cell death-ligand 1 (PD-L1) expression levels were associated with the prognosis of MTX-LPD after MTX discontinuation.<br> Methods A total of 72 Japanese patients diagnosed with MTX-LPD were clinicopathologically analyzed, and immunohistochemical staining of PD-L1 was performed in 20 DLBCL-type and 24 CHL-type MTX-LPD cases to compare with the clinical course. <br> Results PD-L1 was expressed in 5.0% (1/20) of patients with DLBCL-type MTX-LPD, whereas it was expressed in 66.7% (16/24) of the patients with CHL-type MTX-LPD in more than 51% of tumor cells. Most CHL-type MTX-LPD patients with high PD-L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD-L1 high- and low-expression CHL-type MTX-LPD. <br> Conclusion PD-L1 expression was significantly higher in patients with CHL-type than DLBCL-type MTX-LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL-type MTX-LPD patients to achieve complete remission. No association was observed between PD-L1 expression levels and clinical findings at diagnosis, suggesting that PD-L1 expression in tumor cells influences the pathogenesis of CHL-type MTX-LPD after MTX discontinuation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Left Hemihepatectomy for Hepatocellular Carcinoma Following Esophagectomy with Retrosternal Gastric Tube Reconstruction for Esophageal Cancer 755 758 EN Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Kuise 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 Yasuo Nagai 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 Shunsuke Tanabe Department of Gastroenterological Surgery, 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 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 Case Report 10.18926/AMO/62818 Approximately 4% of patients with esophageal cancer develop a second primary malignancy in the upper gastrointestinal trunk. However, hepatectomy following esophagectomy for esophageal cancer has rarely been reported. We report the case of a 70-year-old man who underwent an esophagectomy for esophageal cancer with retrosternal gastric tube reconstruction. Nine years later, he developed hepatocellular carcinoma with tumor thrombus involving the left portal vein, and was successfully treated with left hemihepatectomy. Special attention should be paid to avoiding incidental injury of the gastric tube as well as the right gastroepiploic artery during the hepatectomy. 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.

Nature Portfolio Acta Medica Okayama 2045-2322 11 1 2021 NB-LRR-encoding genes conferring susceptibility to organophosphate pesticides in sorghum 19828 EN Zihuan Jing Institute of Plant Science and Resources, Okayama University Fiona W. Wacera Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Hideki Takanashi Graduate School of Agricultural and Life Sciences, The University of Tokyo Fumi Fukada Institute of Plant Science and Resources, Okayama University Yoji Kawano Institute of Plant Science and Resources, Okayama University Hiromi Kajiya-Kanegae Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization Hiroyoshi Iwata Graduate School of Agricultural and Life Sciences, The University of Tokyo Nobuhiro Tsutsumi Graduate School of Agricultural and Life Sciences, The University of Tokyo Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Organophosphate is the commonly used pesticide to control pest outbreak, such as those by aphids in many crops. Despite its wide use, however, necrotic lesion and/or cell death following the application of organophosphate pesticides has been reported to occur in several species. To understand this phenomenon, called organophosphate pesticide sensitivity (OPS) in sorghum, we conducted QTL analysis in a recombinant inbred line derived from the Japanese cultivar NOG, which exhibits OPS. Mapping OPS in this population identified a prominent QTL on chromosome 5, which corresponded to Organophosphate-Sensitive Reaction (OSR) reported previously in other mapping populations. The OSR locus included a cluster of three genes potentially encoding nucleotide-binding leucine-rich repeat (NB-LRR, NLR) proteins, among which NLR-C was considered to be responsible for OPS in a dominant fashion. NLR-C was functional in NOG, whereas the other resistant parent, BTx623, had a null mutation caused by the deletion of promoter sequences. Our finding of OSR as a dominant trait is important not only in understanding the diversified role of NB-LRR proteins in cereals but also in securing sorghum breeding free from OPS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Accuracy of Acetabular Cup Implantation, as a Function of Body Mass Index and Soft-tissue Thickness, with a Mechanical Intraoperative Support Device: A Retrospective Observational Study 575 583 EN Hayato Suzuki Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Norio Imai Division of Comprehensive Musculoskeletal Medcine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Naoto Endo Division of Orthopedic Surgery, Niigata Prefectural Tsubame Rosai Hospital Original Article 10.18926/AMO/62770 HipCOMPASS, a mechanical intraoperative support device used in total hip arthroplasty (THA), improves the cup-alignment accuracy. However, the alignment accuracy achieved by HipCOMPASS has not been specifically examined in obese patients. In this study, we retrospectively evaluated the relation between alignment accuracy and several obesity-related parameters in 448 consecutive patients who underwent primary THA using HipCOMPASS. We used computed tomography (CT) to measure the preoperative soft-tissue thickness of the anterior-superior iliac spine (ASIS) and pubic symphysis and the differences between preoperative and postoperative cup angle based on the cup-alignment error. We found significant correlations between the absolute value of radiographic anteversion difference and body mass index (r = 0.205), ASIS thickness (r = 0.419), and pubic symphysis thickness (r = 0.434). The absolute value of radiographic inclination difference was significantly correlated with ASIS (r = 0.257) and pubic symphysis thickness (r = 0.202). The receiver operating characteristic curve showed a pubic symphysis thickness of 37.2 mm for a ≥ 5° implantation error in both radiographic inclination and anteversion simultaneously. The cup-alignment error for HipCOMPASS was large in patients whose pubic symphysis thickness was ≥ 37.2 mm on preoperative CT. Our results indicate that methods other than HipCOMPASS, including computed tomography-based navigation systems, might be preferable in obese patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 5 2021 Clinical Manifestations of Patients with Influenza Differ by Age : A Prospective, Multi-centered Study in the Setouchi Marine Area 567 574 EN Ryosuke Takase 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 Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroko Ogawa 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 Hitomi Kataoka 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 Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62769 Influenza potentially has a high mortality rate when it affects the elderly. We aimed to examine the differences in clinical manifestations in patients with influenza according to their age. This multicenter prospective study was performed in six medical institutions in Okayama and Kagawa prefectures (Japan). Between December 1, 2019 and March 31, 2020, we collected data on adult patients diagnosed with influenza type A, who were strat-ified into younger (20-49 years), middle-aged (50-64 years), and older groups (≥ 65 years). We compared the presence or absence of fever, respiratory symptoms, and extrapulmonary symptoms according to age group. In total, 203 patients (113, younger; 51, middle-aged; and 39, older) were eligible for the analysis. The maxi-mum body temperature and temperature at first physician visit in the older group were significantly lower than those in the younger group. The incidence of respiratory symptoms was not different among the three groups. Chills, muscle pain, and arthralgia as systemic symptoms were noted significantly more frequently in the younger (80.9%) and middle-aged (75.5%) groups than in the older group (51.3%) (p = 0.002). Fever and sys-temic symptoms were less likely to appear in older patients, possibly resulting in the delaying of hospital visits among older adults. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 17 2021 Immunoelectron Microscopic Characterization of Vasopressin-Producing Neurons in the Hypothalamo-Pituitary Axis of Non-Human Primates by Use of Formaldehyde-Fixed Tissues Stored at-25 degrees C for Several Years 9180 EN Akito Otubo Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Sho Maejima Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Takumi Oti Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Keita Satoh Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Yasumasa Ueda Department of Physiology, Kyoto Prefectural University of Medicine John F. Morris Department of Physiology, Anatomy & Genetics, University of Oxford, South Parks Road Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Translational research often requires the testing of experimental therapies in primates, but research in non-human primates is now stringently controlled by law around the world. Tissues fixed in formaldehyde without glutaraldehyde have been thought to be inappropriate for use in electron microscopic analysis, particularly those of the brain. Here we report the immunoelectron microscopic characterization of arginine vasopressin (AVP)-producing neurons in macaque hypothalamo-pituitary axis tissues fixed by perfusion with 4% formaldehyde and stored at -25 degrees C for several years (4-6 years). The size difference of dense-cored vesicles between magnocellular and parvocellular AVP neurons was detectable in their cell bodies and perivascular nerve endings located, respectively, in the posterior pituitary and median eminence. Furthermore, glutamate and the vesicular glutamate transporter 2 could be colocalized with AVP in perivascular nerve endings of both the posterior pituitary and the external layer of the median eminence, suggesting that both magnocellular and parvocellular AVP neurons are glutamatergic in primates. Both ultrastructure and immunoreactivity can therefore be sufficiently preserved in macaque brain tissues stored long-term, initially for light microscopy. Taken together, these results suggest that this methodology could be applied to the human post-mortem brain and be very useful in translational research. 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.

Oxford University Press (OUP) Acta Medica Okayama 1471-9053 62 3 2021 Mutations in a Golden2-Like Gene Cause Reduced Seed Weight in Barley albino lemma 1 Mutants 447 457 EN Shin Taketa Institute of Plant Science and Resources, Okayama University Momoko Hattori Institute of Plant Science and Resources, Okayama University Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Eiko Himi Institute of Plant Science and Resources, Okayama University Wataru Sakamoto IInstitute of Plant Science and Resources, Okayama University The albino lemma 1 (alm1) mutants of barley (Hordeum vulgare L.) exhibit obvious chlorophyll-deficient hulls. Hulls are seed-enclosing tissues on the spike, consisting of the lemma and palea. The alm1 phenotype is also expressed in the pericarp, culm nodes and basal leaf sheaths, but leaf blades and awns are normal green. A single recessive nuclear gene controls tissue-specific alm1 phenotypic expression. Positional cloning revealed that the ALM1 gene encodes a Golden 2-like (GLK) transcription factor, HvGLK2, belonging to the GARP subfamily of Myb transcription factors. This finding was validated by genetic evidence indicating that all 10 alm1 mutants studied had a lesion in functionally important regions of HvGLK2, including the three alpha-helix domains, an AREAEAA motif and the GCT box. Transmission electron microscopy revealed that, in lemmas of the alm1.g mutant, the chloroplasts lacked thylakoid membranes, instead of stacked thylakoid grana in wild-type chloroplasts. Compared with wild type, alm1.g plants showed similar levels of leaf photosynthesis but reduced spike photosynthesis by 34%. The alm1.g mutant and the alm1.a mutant showed a reduction in 100-grain weight by 15.8% and 23.1%, respectively. As in other plants, barley has HvGLK2 and a paralog, HvGLK1. In flag leaves and awns, HvGLK2 and HvGLK1 are expressed at moderate levels, but in hulls, HvGLK1 expression was barely detectable compared with HvGLK2. Barley alm1/Hvglk2 mutants exhibit more severe phenotypes than glk2 mutants of other plant species reported to date. The severe alm1 phenotypic expression in multiple tissues indicates that HvGLK2 plays some roles that are nonredundant with HvGLK1. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 11 1 2021 The gastrin-releasing peptide/bombesin system revisited by a reverse-evolutionary study considering Xenopus 13315 EN Asuka Hirooka Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Mayuko Hamada Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Daiki Fujiyama Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Keiko Takanami Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Yasuhisa Kobayashi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Takumi Oti Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Yukitoshi Katayama Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Bombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phylogenetic viewpoint using a newly established genetic database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the 'gut-brain peptide' systems. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Embedding of Epiretinal Proliferation for a Secondary Lamellar Macular Hole 12 Years after Rhegmatogenous Retinal Detachment Repair 391 395 EN Miyuki Fujiwara Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Doi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Takahashi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki 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 Case Report 10.18926/AMO/62236 A 58-year-old Japanese man underwent vitrectomy for rhegmatogenous retinal detachment (RRD) in 2002. Twelve years later, optical coherence tomography revealed the development of a lamellar macular hole; the visual acuity was 20/200. Two years later, because metamorphopsia and the foveal retina thinning were aggravated, epiretinal proliferation embedding was performed to restore the foveal structure by transplanting glial cells to the foveal cavity. The patient was followed-up for 4 years, and his macular morphology and visual acuity (20/66) improved. No complications occurred. This appears to be the first report of epiretinal proliferation embedding for a lamellar macular hole post-RRD repair. 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 Efficacy and Safety of Early Intravenous Landiolol on Myocardial Salvage in Patients with ST-segment Elevation Myocardial Infarction before Primary Percutaneous Coronary Intervention: A Randomized Study 289 297 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa 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 Atsushi Mori Department of Cardiology, Tsuyama Central Hospital Masaki Yoshikawa Department of Cardiology, Fukuyama City Hospital Takefumi Oka Department of Cardiology, Tsuyama Central Hospital Keishi Ichikawa 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 Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62220 Early treatment with an oral β-blocker is recommended in patients with a ST-segment–elevation myocardial infarction (STEMI). In this multicenter study, we evaluated the effects of a continuous administration of landiolol, an ultrashort-acting β-blocker, before primary percutaneous coronary intervention (PCI) on myocardial salvage and its safety in STEMI patients. A total of 47 Japanese patients with anterior or lateral STEMI undergoing a primary PCI within 12 h of symptom onset were randomized to receive intravenous landiolol (started at 3 μg/min/kg dose and continued to a total of 50 mg; n=23) or not (control; n=24). Patients with Killip class III or more were excluded. The primary outcome was the myocardial salvage index on cardiac magnetic resonance imaging (MRI) performed 5-7 days after the PCI. Cardiac MRI was performed in 35 patients (74%). The myocardial salvage index in the landiolol group was significantly greater than that in the control group (44.4±14.6% vs. 31.7±18.9%, respectively; p=0.04). There were no significant differences in adverse events at 24 h between the landiolol and control groups. A continuous administration of landiolol before a primary PCI may increase the degree of myocardial salvage without additional hemodynamic adverse effects within the first 24 h after STEMI. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Effects of Gram-negative Rod Blood Stream Infection on Acute GVHD in Allogeneic Hematopoietic Stem Cell Transplantation: A Single-institute Analysis 279 287 EN Masa-aki Nishinohara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noboru Asada 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 Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Fujii 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 Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62219 A bloodstream infection (BSI) is the most common serious infectious complication of hematopoietic stem cell transplantation (HSCT). BSI promotes an inflammatory state, which exacerbates acute graft-versus-host disease (GVHD). We investigated whether a Gram-negative rod bloodstream infection (GNR-BSI), which develops early after allo-HSCT, affected the onset or exacerbated acute GVHD in 465 patients who underwent allo-HSCT from 1995 through 2015 at a single institution. Eighty-eight patients (19%) developed BSI during the study period. Among the cultures, 50 (57%) were Gram-positive cocci (GPC) and 31 (35%) were GNR. Of the 465 patients, 187 (40%) developed acute GVHD of grade II or higher within the first 100 days post-allogeneic HSCT: 124 (27%) had acute GVHD grade II, 47 (10%) had grade III, and 16 (3%) had grade IV. Multivariate analysis revealed that GNR-BSI was a significant risk factor for grade II-IV acute GVHD (grade II-IV: hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.03-2.97; grade III-IV: HR 2.37, 95% CI 1.03-5.43). These results suggest that GNR-BSI may predict the onset and exacerbation of acute GVHD. No potential conflict of interest relevant to this article was reported.

Oxford Univ Press Acta Medica Okayama 1461-1457 24 5 2020 Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus 367 382 EN Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuji Yada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Hashimoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes' functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2021 High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4 EN Yumi Sakamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 5 2021 Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma 766 EN Atsuko Nasu Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Hospital Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Misa Sakamoto Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuria Egusa Division of Pathophysiology, Okayama University Graduate School of Health Sciences Azusa Fujita Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Differentiation between adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is often challenging based on pathological findings alone. Although serum anti-HTLV-1 antibody positivity is required for ATLL diagnosis, this information is often not available at the time of pathological diagnosis. Therefore, we examined whether the expression of SOX4 and p16 would be helpful for differentiating the two disease entities. We immunohistochemically examined SOX4 and p16 expression (which have been implicated in ATLL carcinogenesis) in 11 ATLL patients and 20 PTCL-NOS patients and classified them into four stages according to the percentage of positive cells. Among the ATLL cases, 8/11 (73%) were SOX4-positive, while only 2/20 (10%) PTCL-NOS cases expressed SOX4. The mean total score was 4.2 (standard deviation (SD): 0.61) in the ATLL group and 0.50 (SD: 0.46) in the PTCL-NOS group (p < 0.001). Positive expression of p16 was noted in 4/11 (36%) patients with ATLL and 3/20 (15%) patients with PTCL-NOS, with mean total scores of 1.9 (SD: 0.64) and 0.70 (SD: 0.48) in the ATLL and PTCL-NOS groups, respectively (p = 0.141). These results suggest that SOX4 may be strongly expressed in ATLL compared to PTCL-NOS cases. Therefore, it may be helpful to perform immunohistochemical staining of SOX4 when pathologists face challenges discriminating between ATLL and PTCL-NOS. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1860-1871 17 2021 Effects of large-scale forest fire followed by illegal logging on the regeneration of boreal forests in Mongolia 267 279 EN Keiji Sakamoto Graduate School of Environmental and Life Science, Okayama University Misaki Tomonari Graduate School of Environmental and Life Science, Okayama University Uyanga Ariya Graduate School of Environmental and Life Science, Okayama University Erika Nakagiri Graduate School of Environmental and Life Science, Okayama University Tetsuya Matsumoto Graduate School of Environmental and Life Science, Okayama University Yasuaki Akaji Center for Environmental Biology and Ecosystem Studies, National Institute for Environmental Studies Takashi Otoda Graduate School of Environmental and Life Science, Okayama University Muneto Hirobe Graduate School of Environmental and Life Science, Okayama University Baatarbileg Nachin School of Engineering and Applied Sciences, National University of Mongolia We aimed to test the hypothesis that large-scale forest fire followed by illegal logging inhibits the regeneration of boreal forests in Mongolia. For this purpose, we compared regeneration of the forest between five stands in a large-scale post-fire site, i.e., (1) undisturbed stand in the unburnt and remaining forest, (2) stand disturbed by illegal logging in the unburnt and remaining forest, (3) stand disturbed by forest fire, (4) stand disturbed by forest fire followed by illegal logging and located in proximity to the remaining forest, which acts as a seed source, and (5) stand disturbed by forest fire followed by illegal logging and located far from the remaining forest, which acts as a seed source. The stand disturbed by logging showed similar species composition of regenerated individuals as the undisturbed stand. In the stand disturbed by logging, Picea obovata and Pinus sibirica were abundant because of advance regeneration on the intact forest floor. In the stand disturbed by forest fire and that disturbed by forest fire followed by illegal logging, Larix sibirica and Betula platyphylla were abundant, and the regenerated individuals of these two species were new individuals after the disturbances. L. sibirica was abundant in the stand disturbed by forest fire because the mother trees survived the forest fire because of their thick bark. B. platyphylla was abundant in the stand disturbed by forest fire followed by illegal logging because the mother trees of L. sibirica were logged and the seeds of B. platyphylla are able to disperse further than that of L. sibirica. However, in the stand disturbed by forest fire followed by illegal logging that was located far from the remaining forest, the regeneration was much reduced because only few seeds, including that of B. platyphylla, were dispersed into this stand and sprouts of B. platyphylla were damaged by the logging operation. In addition, the regeneration of L. sibirica and B. platyphylla was likely to have been reduced for several years after the forest fire because of the loss of safe sites for their invasion by the changes of the forest floor conditions. Therefore, it is likely that large-scale forest fires that are followed by illegal logging inhibit the regeneration in many parts of the post-fire site and those parts will change into open forests of B. platyphylla or grassland. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 1 2021 令和元年度岡山医学会賞 脳神経研究奨励賞（新見賞） 4 6 EN Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

ASME International Acta Medica Okayama 0094-9930 143 2 2020 Prediction of the Fracture Location by Tensile Tests of Gray Cast Iron Based on the Dimensional Changes of Graphite Flakes 021502 EN Naoya Tada Graduate School of Natural Science and Technology, Okayama University Takeshi Uemori Graduate School of Natural Science and Technology, Okayama University Junji Sakamoto Graduate School of Natural Science and Technology, Okayama University Gray cast iron has been used as a component in various mechanical parts, such as the blocks and heads of automobile and marine engines, cylinder liners for internal combustion engines, and machine tool bases. It is desirable because of its good castability and machinability, damping characteristics, and high performance-to-cost ratio. On the other hand, weak graphite flakes present in gray cast iron serve as stress concentrators and adversely affect the material strength. Therefore, it is crucial to examine the relationship between the distribution of graphite flakes and the strength or fracture of gray cast iron. In this study, tensile tests on gray cast iron were carried out using a plate specimen and observed by scanning electron microscopy, and the microscopic deformation was observed on the specimen surface. Particularly, the change in the size of graphite flakes during the tensile tests was examined, and the observed trend was discussed. The experimental results reveal that the dimensional changes in the graphite flakes vary in the observed area and that the final fracture occurs in an area where a large dimensional change is observed, suggesting that the fracture location or critical parts of gray cast iron can be predicted from the dimensional changes of the graphite flakes at an early stage of deformation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 7 2021 In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats 3400 EN Daisuke Uta Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama Takumi Oti Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain-spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Laparoscopic Hepatectomy for the Patient with Hemophilia A with High Titer Factor VIII Inhibitor 199 204 EN Tatsuo Matsuda 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 Kazuhiro Yoshida Department of Gastroenterological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadakazu Matsuda Department of Surgery, Matsuda Hospital Masatoshi Uno Department of Internal Medicine, Kaneda Hospital Masaya Abe Department of Hematology and Oncology,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noboru Asada Department of Hematology and Oncology,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 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 Case Report 10.18926/AMO/61901 We present the first case of laparoscopic left lateral segmentectomy for hepatocellular carcinoma (HCC) in a patient with hemophilia A, acquired hepatitis C, and high-titer factor VIII inhibitor, which was confirmed by preoperative diagnosis. He underwent laparoscopic left lateral segmentectomy with the administration of recombinant activated factor VII. Surgery could be performed with reduced intraoperative hemorrhage. He experienced postoperative intra-abdominal wall hemorrhage, which was successfully managed with red cell concentrates transfusion and administration of recombinant activated factor VII. Laparoscopic hepatectomy can be applied for hemophilia patients with high titer inhibitors. No potential conflict of interest relevant to this article was reported.

岡山大学大学院ヘルスシステム統合科学研究科 Acta Medica Okayama 2436-3227 1 2021 遠隔での見守りのための機器・サービスの調査と訪問看護での利用を想定した分類 47 63 EN Toshio Sakamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akina Hirata Yell Co., Ltd. Mizuki Morita Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University 10.18926/interdisciplinary/61889 This study aims to improve the quality of home nursing care for the elderly. The report presents web-based information about devices and services for remote monitoring and health management using information and communication technology and about how they can improve home care nursing station efficiency in Japan. The search terms "elderly people," "watch over," and "service," plus "sensor" were used to narrow the search. After repeating the search using a chained search for materials and links extracted from those search results, services for home care stations particularly addressing the remote monitoring of elderly people were selected and extracted. Early detection of abnormalities for support by home health nurse responsibilities for observing the general condition of the patient was chosen as the main evaluation index of usefulness. The contractor and service cost were secondary evaluation axes. Results show 9 information communication devices and services for real-time monitoring of the elderly persons’ vital signs in real time for 24 hr, 2 of which are highly useful for early detection of abnormalities and subsequent response. Results suggest that other services might be more useful, depending on how they are used, and that general-purpose services with minimum functions and low cost of introduction and maintenance can provide more opportunities for utilization. Providing these services on a BtoBtoC model and responding to patients’ medical needs can supplement home care nursing station work, increase human resource and time efficiencies, and give patients "the feeling that a nurse is always at their bedside,” even when far away. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Evaluation of the Imaging Process for a Novel Subtraction Method Using Apparent Diffusion Coefficient Values 139 145 EN Kentaro Hamada Radiological Technology, Graduate School of Health Sciences, Okayama University Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Yuuki Yoshimura Radiological Technology, Graduate School of Health Sciences, Okayama University Abdullah Khasawneh Department of Oral and Maxillofacial Radiology, Okayama University Hospital Majd Barham Department of Oral and Maxillofacial Radiology, Okayama University Hospital Nouha Tekiki Department of Oral and Maxillofacial Radiology, Okayama University Hospital Irfan Sugianto Department of Oral and Maxillofacial Radiology, Okayama University Hospital Babatunde O. Bamgbose Department of Oral and Maxillofacial Radiology, Okayama University Hospital Kohei Konishi Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Hinata Ishizaka 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 Hospital Original Article 10.18926/AMO/61880 Diffusion-weighted imaging may be used to obtain the apparent diffusion coefficient (ADC), which aids the diagnosis of cerebral infarction and tumors. An ADC reflects elements of free diffusion. Diffusion kurtosis imaging (DKI) has attracted attention as a restricted diffusion imaging technique. The ADC subtraction method (ASM) was developed to visualize restricted diffusion with high resolution by using two ADC maps taken with different diffusion times. We conducted the present study to provide a bridge between the reported basic ASM research and clinical research. We developed new imaging software for clinical use and evaluated its performance herein. This software performs the imaging process automatically and continuously at the pixel level, using ImageJ software. The new software uses a macro or a plugin which is compatible with various operating systems via a Java Virtual Machine. We tested the new imaging software’s performance by using a Jurkat cell bio-phantom, and the statistical evaluation of the performance clarified that the ASM values of 99.98% of the pixels in the bio-phantom and physiological saline were calculated accurately (p<0.001). The new software may serve as a useful tool for future clinical applications and restricted diffusion imaging research. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 26663643 2 1 2021 Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations 100107 EN Kiichiro Ninomiya Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shunsuke Teraoka Internal Medicine III, Wakayama Medical University Yoshitaka Zenke Department of Thoracic Oncology, National Cancer Center Hospital East Hirotsugu Kenmotsu Division of Thoracic Oncology, Shizuoka Cancer Center Yukiko Nakamura Department of Respiratory Medicine, Yokohama Municipal Citizen’s Hospital Yusuke Okuma Department of Thoracic Oncology, National Cancer Center Hospital Akihiro Tamiya Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center Kaname Nosaki Department of Thoracic Oncology, National Cancer Center Hospital East Masahiro Morise Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Keiju Aokage Department of Thoracic Surgery, National Cancer Center Hospital East Yuko Oya Department of Thoracic Oncology, Aichi Cancer Center Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center Tomohiro Sakamoto Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University Kentaro Tanaka Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Junko Tanizaki Department of Medical Oncology, Kishiwada City Hospital Satoru Miura Department of Internal Medicine, Niigata Cancer Center Hospital Hideaki Mizutani Department of Thoracic Oncology, Saitama Cancer Center Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Ou Yamaguchi Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center Noriyuki Ebi Department of Respiratory Oncology, Iizuka Hospital Yasushi Goto Department of Thoracic Oncology, National Cancer Center Hospital Takaaki Sasaki Respiratory Center, Asahikawa Medical University Haruko Daga Department of Medical Oncology, Osaka City General Hospital Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine Kyoto University Takeharu Yamanaka Department of Biostatistics, Yokohama City University School of Medicine Shinsuke Amano Japan Federation of Cancer Patient Groups Kazuo Hasegawa Japan Lung Cancer Alliance Chiyo K. Imamura Advanced Cancer Translational Research Institute, Showa University Kenichi Suzuki Division of Applied Pharmaceutical Education and Research, Hoshi University Kazuko Nakajima Department of Nursing and The Division of Stem Cell Transplantation, Shizuoka Cancer Center Hitomi Nishimoto Department of Nursing, Okayama University Hospital Satoshi Oizumi Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center Toyoaki Hida Department of Thoracic Oncology, Aichi Cancer Center Hospital Katsuyuki Hotta Center for Clinical Oncology, Okayama University Hospital Yuichi Takiguchi Department of Medical Oncology, Chiba University Hospital Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2407 21 1 2021 Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation 102 EN Atene Ito 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 Shuichi Sakamoto 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 Hiroki Kajioka Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshimoto 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 Shinji Kuroda 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 Hiroshi Tazawa 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</br> Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated.</br> Methods</br> The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored.</br> Results</br> Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein.</br> Conclusion</br> EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Needle Tract Ablation in Liver Tissue Using a Cryoprobe Combined with an Electrosurgical Device: Influence of ex vivo and in vivo Animal Models 9 14 EN Hideo Gobara Division of Medical Informatics, Okayama University Hospital Akira Yamamoto Department of Diagnostic and Interventional Radiology, Osaka City University Graduate School of Medicine Toshiyuki Komakic Department of Radiology, Okayama University Hospital Toshiaki Kitayama Department of Radiology, Otemae Hospital Jun Sakurai Center for Innovative Clinical Medicine, Okayama University Hospital Toshihiro Iguchi Department of Radiology, Okayama University Hospital Yusuke Matsui Department of Radiology, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Hospital Koji Tomita Department of Radiology, Okayama University Hospital Takao Hiraki 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 Original Article 10.18926/AMO/61428 To assess the feasibility of needle tract ablation in liver tissue in ex vivo and in vivo animal models using a cryo-probe and electrosurgical device. The experimental device is made by inserting a cryoprobe through an intro-ducer sheath for insulation, with 2-cm of probe tip projecting out. A beagle liver was punctured by the device, and electric current was applied at 30-W with the electrosurgical knife touching the non-insulated device base. The discolored area of cut surface along the device was evaluated in 5 application-time groups (5 , 10 , 15 , 20, or 25 seconds). An ex vivo experiment was performed to determine an ablation algorithm with an appropriate application time by comparison with radiofrequency ablation (RFA) results. Thereafter, an in vivo experiment was performed to verify the algorithm’s feasibility. In the ex vivo model, the cut surface demonstrated different amounts of discolored area according to the application time. The total discolored area in the 20-seconds group was similar to that by RFA. In the in vivo model, the liver did not bleed, the total discolored area was similar to that ex vivo, and coagulation necrosis was confirmed by photomicrograph. Needle tract ablation can be per-formed using the experimental device and electrosurgical device. 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.

Wiley Acta Medica Okayama 0953-8194 32 8 2020 Vasopressin gene products are colocalised with corticotrophin‐releasing factor within neurosecretory vesicles in the external zone of the median eminence of the Japanese macaque monkey (Macaca fuscata) e12875 EN Akito Otubo Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Natsuko Kawakami Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Sho Maejima Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Yasumasa Ueda Department of Physiology, Kyoto Prefectural University of Medicine John F. Morris Department of Physiology, Anatomy & Genetics, University of Oxford Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Arginine vasopressin (AVP), when released into portal capillaries with corticotrophin‐releasing factor (CRF) from terminals of parvocellular neurones of the hypothalamic paraventricular nucleus (PVH), facilitates the secretion of adrenocorticotrophic hormone (ACTH) in stressed rodents. The AVP gene encodes a propeptide precursor containing AVP, AVP‐associated neurophysin II (NPII), and a glycopeptide copeptin, although it is currently unclear whether copeptin is always cleaved from the neurophysin and whether the NPII and/or copeptin have any functional role in the pituitary. Furthermore, for primates, it is unknown whether CRF, AVP, NPII and copeptin are all colocalised in neurosecretory vesicles in the terminal region of the paraventricular CRF neurone axons. Therefore, we investigated, by fluorescence and immunogold immunocytochemistry, the cellular and subcellular relationships of these peptides in the CRF‐ and AVP‐producing cells in unstressed Japanese macaque monkeys (Macaca fuscata). Reverse transcription‐polymerase chain reaction analysis showed the expression of both CRF and AVP mRNAs in the monkey PVH. As expected, in the magnocellular neurones of the PVH and supraoptic nucleus, essentially no CRF immunoreactivity could be detected in NPII‐immunoreactive (AVP‐producing) neurones. Immunofluorescence showed that, in the parvocellular part of the PVH, NPII was detectable in a subpopulation (approximately 39%) of the numerous CRF‐immunoreactive neuronal perikarya, whereas, in the outer median eminence, NPII was more prominent (approximately 52%) in the CRF varicosities. Triple immunoelectron microscopy in the median eminence demonstrated the presence of both NPII and copeptin immunoreactivity in dense‐cored vesicles of CRF‐containing axons. The results are consistent with an idea that the AVP propeptide is processed and NPII and copeptin are colocalised in hypothalamic‐pituitary CRF axons in the median eminence of a primate. The CRF, AVP and copeptin are all co‐packaged in neurosecretory vesicles in monkeys and are thus likely to be co‐released into the portal capillary blood to amplify ACTH release from the primate anterior pituitary. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0166-8595 147 1 2021 Phos-tag-based approach to study protein phosphorylation in the thylakoid membrane 107 124 EN Keiji Nishioka Institute of Plant Science and Resources (IPSR), Okayama University Yusuke Kato Institute of Plant Science and Resources (IPSR), Okayama University Shin-ichiro Ozawa Institute of Plant Science and Resources (IPSR), Okayama University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Wataru Sakamoto Institute of Plant Science and Resources (IPSR), Okayama University Protein phosphorylation is a fundamental post-translational modification in all organisms. In photoautotrophic organisms, protein phosphorylation is essential for the fine-tuning of photosynthesis. The reversible phosphorylation of the photosystem II (PSII) core and the light-harvesting complex of PSII (LHCII) contribute to the regulation of photosynthetic activities. Besides the phosphorylation of these major proteins, recent phosphoproteomic analyses have revealed that several proteins are phosphorylated in the thylakoid membrane. In this study, we utilized the Phos-tag technology for a comprehensive assessment of protein phosphorylation in the thylakoid membrane of Arabidopsis. Phos-tag SDS-PAGE enables the mobility shift of phosphorylated proteins compared with their non-phosphorylated isoform, thus differentiating phosphorylated proteins from their non-phosphorylated isoforms. We extrapolated this technique to two-dimensional (2D) SDS-PAGE for detecting protein phosphorylation in the thylakoid membrane. Thylakoid proteins were separated in the first dimension by conventional SDS-PAGE and in the second dimension by Phos-tag SDS-PAGE. In addition to the isolation of major phosphorylated photosynthesis-related proteins, 2D Phos-tag SDS-PAGE enabled the detection of several minor phosphorylated proteins in the thylakoid membrane. The analysis of the thylakoid kinase mutants demonstrated that light-dependent protein phosphorylation was mainly restricted to the phosphorylation of the PSII core and LHCII proteins. Furthermore, we assessed the phosphorylation states of the structural domains of the thylakoid membrane, grana core, grana margin, and stroma lamella. Overall, these results demonstrated that Phos-tag SDS-PAGE is a useful biochemical tool for studying in vivo protein phosphorylation in the thylakoid membrane protein. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0304-3835 497 2021 Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis 1 3 EN Hiroki Kajioka 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 Atene Ito Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuichi Sakamoto 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 Shinji Kuroda 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 Yuzo Umeda 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 Hiroshi Tazawa 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 Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 C-Arm-Free Minimally Invasive Cervical Pedicle Screw Fixation (MICEPS): A Technical Note 551 556 EN Masato Tanaka 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 Venkatesh Kadiri Department of Orthopaedic Surgery, Okayama Rosai Hospital Taro Yamauchi Department of Orthopaedic Surgery, Okayama Rosai Hospital Case Report 10.18926/AMO/61216 A minimally invasive posterolateral approach designed to avoid the lateral misplacement of midcervical pedicle screws was reported, but there is no technical report that describes this technique without C-arm fluoroscopy. We report the results of a 2.5 years follow-up of a 62-year-old female patient with C4 metastatic breast cancer. The patient suffered from severe neck pain and impending quadriplegia for 2 months after radiation therapy. We performed C-arm-free minimally invasive cervical pedicle screw fixation (MICEPS). The patient was suc-cessfully treated with surgery, and her neck pain was well controlled. She had neither neurological deficits nor neck pain at the final (2.5-year) follow-up. C-arm-free MICEPS is a useful technique; in addition, the sur-geons and staff have no risk of radiation exposure, there is a reduced need for postoperative imaging, and a decreased revision rate can be expected with C-arm-free MICEPS. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2589-0042 23 10 2020 Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons 101648 EN Takashi Miyata Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Daisuke Hagiwara Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Yuichi Hodai Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Tsutomu Miwata Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Yohei Kawaguchi Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Junki Kurimoto Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Hajime Ozaki Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Kazuki Mitsumoto Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Hiroshi Takagi Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Hidetaka Suga Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Tomoko Kobayashi Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Mariko Sugiyama Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Takeshi Onoue Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Yoshihiro Ito Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Shintaro Iwama Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Ryoichi Banno Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Mami Matsumoto Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences Natsuko Kawakami Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences Nobuhiko Ohno Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University, School of Medicine Hirotaka Sakamoto Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University Hiroshi Arima Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0960-9822 31 1 2020 Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord 103 114.e5 EN Takumi Oti Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Keita Satoh Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Daisuke Uta Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama Junta Nagafuchi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Sayaka Tateishi Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Ryota Ueda Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Keiko Takanami Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Larry J. Young Center for Translational Social Neuroscience, Silvio O. Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University Antony Galione Department of Pharmacology, University of Oxford John F. Morris Department of Physiology, Anatomy & Genetics, University of Oxford Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Oxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion―a localized volume transmission―to reach oxytocin receptors on GRP neurons and facilitate male sexual function. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 21 18 2020 Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids 6748 EN Yukitoshi Katayama Ushimado Marine Institute, Faculty of Science, Okayama University Kazuhiro Saito Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Some fish have acquired the ability to breathe air, but these fish can no longer flush their gills effectively when out of water. Hence, they have developed characteristic means for defense against external stressors, including thirst (osmolarity/ions) and toxicity. Amphibious fish, extant air-breathing fish emerged from water, may serve as models to examine physiological responses to these stressors. Some of these fish, including mudskipper gobies such asPeriophthalmodon schlosseri,Boleophthalmus boddartiand ourPeriophthalmus modestus, display distinct adaptational behaviors to these factors compared with fully aquatic fish. In this review, we introduce the mudskipper goby as a unique model to study the behaviors and the neuro/endocrine mechanisms of behavioral responses to the stressors. Our studies have shown that a local sensation of thirst in the buccal cavity-this being induced by dipsogenic hormones-motivates these fish to move to water through a forebrain response. The corticosteroid system, which is responsive to various stressors, also stimulates migration, possibly via the receptors in the brain. We suggest that such fish are an important model to deepen insights into the stress-related neuro/endocrine-behavioral effects. No potential conflict of interest relevant to this article was reported.

Springer, Dordrecht Acta Medica Okayama 2013 DroidTrack: Tracking Information Diffusion and Preventing Information Leakage on Android 243 251 EN Syunya Sakamoto Graduate School of Natural Science and Technology, Okayama University An app in Android can collaborate with other apps and control personal information by using the Intent or user’s allowing of permission. However, users cannot detect when they communicate. Therefore, users might not be aware information leakage if app is malware. This paper proposes DroidTrack, a method for tracking the diffusion of personal information and preventing its leakage on an Android device. DroidTrack alerts the user of the possibility of information leakage when an app uses APIs to communicate with outside. These alerts are triggered only if the app has already called APIs to collect personal information. Users are given the option to refuse the execution of the API if it is not appropriate. Further, by illustrating how their personal data is diffused, users can have the necessary information to help them decide whether the API use is appropriate. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Study Protocol for Assessing the Efficacy of Compression Therapy Using Stockings and Sleeves to Prevent Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients 455 459 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 Kengo Kanetaka 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 Clinical Study Protocol 10.18926/AMO/60808 Taxanes are key drugs for patients with breast cancer. A major adverse effect associated with the administration of the taxane docetaxel is chemotherapy-induced peripheral neuropathy (CIPN). We are conducting a singlecenter, single-arm, open-label historical control trial to evaluate the ability of compression therapy using stockings or sleeves to prevent CIPN due to docetaxel treatment. The primary endpoint is the incidence of all-grade CIPN according to patients’ records until 3 weeks after the fourth docetaxel administration. This study’s results will clarify whether compression therapy using stockings or sleeves can prevent CIPN in breast cancer patients. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0021-9967 529 7 2020 Variation of pro‐vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin‐related glycopeptide copeptin 1372 1390 EN Natsuko Kawakami Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Akito Otubo Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Sho Maejima Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Ashraf H. Talukder Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University Keita Satoh Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Takumi Oti Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Keiko Takanami Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Yasumasa Ueda Department of Physiology, Kyoto Prefectural University of Medicine Keiichi Itoi Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University John F. Morris Department of Physiology, Anatomy and Genetics, University of Oxford Tatsuya Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University Arginine vasopressin (AVP) is synthesized in parvocellular‐ and magnocellular neuroendocrine neurons in the paraventricular nucleus (PVN) of the hypothalamus. Whereas magnocellular AVP neurons project primarily to the posterior pituitary, parvocellular AVP neurons project to the median eminence (ME) and to extrahypothalamic areas. The AVP gene encodes pre‐pro‐AVP that comprises the signal peptide, AVP, neurophysin (NPII), and a copeptin glycopeptide. In the present study, we used an N‐terminal copeptin antiserum to examine copeptin expression in magnocellular and parvocellular neurons in the hypothalamus in the mouse, rat, and macaque monkey. Although magnocellular NPII‐expressing neurons exhibited strong N‐terminal copeptin immunoreactivity in all three species, a great majority (~90%) of parvocellular neurons that expressed NPII was devoid of copeptin immunoreactivity in the mouse, and in approximately half (~53%) of them in the rat, whereas in monkey hypothalamus, virtually all NPII‐immunoreactive parvocellular neurons contained strong copeptin immunoreactivity. Immunoelectron microscopy in the mouse clearly showed copeptin‐immunoreactivity co‐localized with NPII‐immunoreactivity in neurosecretory vesicles in the internal layer of the ME and posterior pituitary, but not in the external layer of the ME. Intracerebroventricular administration of a prohormone convertase inhibitor, hexa‐d‐arginine amide resulted in a marked reduction of copeptin‐immunoreactivity in the NPII‐immunoreactive magnocellular PVN neurons in the mouse, suggesting that low protease activity and incomplete processing of pro‐AVP could explain the disproportionally low levels of N‐terminal copeptin expression in rodent AVP (NPII)‐expressing parvocellular neurons. Physiologic and phylogenetic aspects of copeptin expression among neuroendocrine neurons require further exploration. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-2392 11 2020 Transcriptomic Analysis of the Kuruma PrawnMarsupenaeus japonicusReveals Possible Peripheral Regulation of the Ovary 541 EN Naoaki Tsutsui Faculty of Science, Ushimado Marine Institute, Okayama University Yasuhisa Kobayashi Faculty of Science, Ushimado Marine Institute, Okayama University Kouichi Izumikawa Research Institute for Fisheries Science, Okayama Prefectural Technology Center for Agriculture, Forestry, and Fisheries Tatsuya Sakamoto Faculty of Science, Ushimado Marine Institute, Okayama University Crustacean reproduction has been hypothesized to be under complex endocrinological regulation by peptide hormones. To further improve our understanding of the mechanisms underlying this complex regulation, knowledge is needed regarding the hormones not only of the central nervous system (CNS) such as the X-organ/sinus gland (XOSG), brain, and thoracic ganglia, but also the peripheral gonadal tissues. For example, in vertebrates, some gonadal peptide hormones including activin, inhibin, follistatin, and relaxin are known to be involved in the reproductive physiology. Therefore, it is highly likely that some peptide factors from the ovary are serving as the signals among peripheral tissues and central nervous tissues in crustaceans. In this work, we sought to find gonadal peptide hormones and peptide hormone receptors by analyzing the transcriptome of the ovary of the kuruma prawnMarsupenaeus japonicus. The generated ovarian transcriptome data led to the identification of five possible peptide hormones, including bursicon-alpha and -beta, the crustacean hyperglycemic hormone (CHH)-like peptide, insulin-like peptide (ILP), and neuroparsin-like peptide (NPLP). Dominant gene expressions for the bursicons were observed in the thoracic ganglia and the ovary, in the CNS for the CHH-like peptide, in the heart for NPLP, and in the ovary for ILP. Since the gene expressions of CHH-like peptide and NPLP were affected by a CHH (Penaeus japonicussinus gland peptide-I) from XOSG, we produced recombinant peptides for CHH-like peptide and NPLP usingEscherichia coliexpression system to examine their possible peripheral regulation. As a result, we found that the recombinant NPLP increased vitellogenin gene expression in incubated ovarian tissue fragments. Moreover, contigs encoding putative receptors for insulin-like androgenic gland factor, insulin, neuroparsin, and neuropeptide Y/F, as well as several contigs encoding orphan G-protein coupled receptors and receptor-type guanylyl cyclases were also identified in the ovarian transcriptome. These results suggest that reproductive physiology in crustaceans is regulated by various gonadal peptide hormones, akin to vertebrates. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0006-291X 531 3 2020 High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4 422 430 EN Yumi Sakamoto Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tatsuo Okui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiyuki Yoneda Department of Cellular and Molecular Biochemistry, Osaka University Graduate School of Dentistry Shoji Ryumon Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tomoya Nakamura Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Kunisada Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Soichiro Ibaragi Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masanori Masui Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kisho Ono Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kyoichi Obata Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Tsuyoshi Shimo Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido Akira Sasaki Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Preoperative Use of Alpha-1 Receptor Blockers in Male Patients Undergoing Extracorporeal Shock Wave Lithotripsy for a Ureteral Calculus 293 299 EN Takashi Yoshioka Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University Kenji Omae Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University Tatsushi Kawada Department of Urology, Onomichi Municipal Hospital Yosuke Inoue Department of Urology, Onomichi Municipal Hospital Morito Sugimoto Department of Urology, Onomichi Municipal Hospital Tadashi Oeda Department of Urology, Onomichi Municipal Hospital Shinya Uehara Department of Urology, Kawasaki Medical School General Medical Center Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunichi Fukuhara Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University Original Article 10.18926/AMO/60367 In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Decreased Serum Antioxidant Marker is Predictive of Early Recurrence in the Same Segment after Radical Ablation for Hepatocellular Carcinoma 275 283 EN Taiko Muro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Nakamura 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 Hideki Onishi 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 Tetsuya Yasunaka 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 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 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/60364 Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a promising method for controlling tumors, although it does not entirely eliminate recurrence. Oxidative stress is associated with the progression of hepatocarcinogenesis, while also acting as an anticancer response. The objective of the present study was to investigate the factors influencing post-RFA outcomes. We recruited 235 newly diagnosed HCC patients who received RFA for single tumors. The patients with recurrence were sub-grouped into early and segmental recurrence groups. The characteristics of the sub-grouped patients were evaluated, including by measuring oxidative stress marker reactive oxygen metabolites and antioxidant marker OXY-adsorbent tests. The factors associated with poor survival were a high Child-Pugh score and early recurrence within 2 years in the same segment. The patients who experienced recurrence within 2 years in the same segment showed a larger tumor diameter than did others. According to a multivariate analysis, the OXY values were also significantly low in these patients. In conclusion, maintaining the antioxidant reservoir function with a high OXY value might be necessary to prevent early recurrence within the RFA-treated segment. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3417 10 14 2020 Finite Element Study of the Effect of Internal Cracks on Surface Profile Change due to Low Loading of Turbine Blade 4883 EN Junji Sakamoto Graduate School of Natural Science and Technology, Okayama University Naoya Tada Graduate School of Natural Science and Technology, Okayama University Takeshi Uemori Graduate School of Natural Science and Technology, Okayama University Hayato Kuniyasu Shimadzu Corporation Turbine blades for thermal power plants are exposed to severe environments, making it necessary to ensure safety against damage, such as crack formation. A previous method detected internal cracks by applying a small load to a target member. Changes in the surface properties of the material were detected before and after the load using a digital holographic microscope and a digital height correlation method. In this study, this technique was applied in combination with finite element analysis using a 2D and 3D model simulating the turbine blades. Analysis clarified that the change in the surface properties under a small load varied according to the presence or absence of a crack, and elucidated the strain distribution that caused the difference in the change. In addition, analyses of the 2D model considering the material anisotropy and thermal barrier coating were conducted. The difference in the change in the surface properties and strain distribution according to the presence or absence of cracks was elucidated. The difference in the change in the top surface height distribution of the materials with and without a crack was directly proportional to the crack length. As the value was large with respect to the vertical resolution of 0.2 nm of the digital holographic microscope, the change could be detected by the microscope. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0927-7757 520 2017 Indocyanine green-laden poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules incorporating reverse micelles: Effects of PEG-b-PLA composition on the nanocapsule diameter and encapsulation efficiency 764 770 EN Takaichi Watanabe Department of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University Yui Sakamoto Department of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University Tetsuya Inooka Division of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Yukitaka Kimura Division of Material and Energy Science, Graduate School of Environmental and Life Science, Okayama University Tsutomu Ono Department of Applied Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University Reverse micelles are thermodynamically stable systems, with a capacity to encapsulate hydrophilic molecules in their nanosized core, which is smaller than the core generally obtained with water-in-oil-emulsion droplets. Herein, we present a simple technique for the preparation of poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules encapsulating a hydrophilic photosensitizer (indocyanine green, ICG), which exploits reverse micelle formation and subsequent emulsion-solvent diffusion. We establish the effect of the PEG-b-PLA composition and the co-surfactant volume on the diameter and water content of the reverse micelles. We demonstrate that the composition of PEG-b-PLA affects also the diameter and encapsulation efficiency of the resulting nanocapsules. We show that the ICG-laden nanocapsules fabricated under the most optimal conditions have a diameter of approximately 100 nm and an ICG encapsulation efficiency of 58%. We believe that the method proposed here is a promising step towards the preparation of hydrophilic drug-laden polymer nanocapsules with a small diameter and therefore suitable for use in drug delivery applications based on enhanced permeability and retention (EPR) effect-driven passive targeting. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 2041-6539 11 23 2020 Carbon-rich materials with three-dimensional ordering at the angstrom level 5866 5873 EN Shixin Fa Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Masanori Yamamoto Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Hirotomo Nishihara Institute of Multidisciplinary Research for Advanced Materials, Tohoku University Ryota Sakamoto Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University Kazuhide Kamiya Graduate School of Engineering Science, Osaka University Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Tomoki Ogoshi Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Carbon-rich materials, which contain over 90% carbon, have been mainly synthesized by the carbonization of organic compounds. However, in many cases, their original molecular and ordered structures are decomposed by the carbonization process, which results in a failure to retain their original three-dimensional (3D) ordering at the angstrom level. Recently, we successfully produced carbon-rich materials that are able to retain their 3D ordering at the angstrom level even after the calcination of organic porous pillar[6]arene supramolecular assemblies and cyclic porphyrin dimer assemblies. Other new pathways to prepare carbon-rich materials with 3D ordering at the angstrom level are the controlled polymerization of designed monomers and redox reaction of graph. Electrocatalytic application using these materials is described. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 0893-3952 33 12 2020 Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer 2437 2448 EN Tomoka Ikeda Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Okayama University Graduate School of Health Sciences Misa Sakamoto Okayama University Graduate School of Health Sciences Tomoyasu Tachibana Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital Asami Nishikori Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Effect of Vonoprazan on Delayed Bleeding after Endoscopic Submucosal Dissection for Gastric Neoplasia among Antithrombotic Drug Users: A Single-Center, Single-Arm Prospective Observational Case Control Study 245 250 EN Shumpei Yamamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Takayama Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Yuichi Shimodate Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Rio Takezawa Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Naoyuki Nishimura Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Akira Doi Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Hirokazu Mouri Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Kazuhiro Matsueda Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Motowo Mizuno Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/59958 Antithrombotic therapy is a major risk factor for delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasia. A potassium-competitive acid blocker, vonoprazan, is expected to prevent delayed bleeding better than conventional proton pomp inhibitors (PPIs), but the evidence is controversial. We sought to clarify the efficacy of vonoprazan for prevention of delayed bleeding after gastric ESD in patients under antithrombotic therapy. We prospectively registered 50 patients who underwent gastric ESD while receiving antithrombotic therapy and vonoprazan in our institution between October 2017 and September 2018. The incidence of delayed bleeding was compared with that in a historical control group of 116 patients treated with conventional PPI. We also evaluated risk factors associated with delayed bleeding. Delayed bleeding was observed in 8 of 50 patients (16.0%), which was not dissimilar from the incidence in the historical control group (12.1%) (p=0.49). In the univariate analysis, age (> 70 years) (p=0.034), multiple antithrombotic drug use (p<0.01), procedure time (> 200 min) (p=0.038) and tumor size (> 40 mm) (p<0.01) were associated with delayed bleeding after gastric ESD, but vonoprazan was not (p=0.49). Vonoprazan may not be more effective than conventional PPIs in preventing delayed bleeding after gastric ESD in patients receiving antithrombotic therapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 A Possible Protective Effect of the 'Cam Deformity' on Femoral Neck Fracture: The Relationship between Hip Morphology and the Types of Hip Fracture 221 227 EN Takuma Yagura Department of Orthopaedic Surgery, Kansai Medical University Kenichi Oe Department of Orthopaedic Surgery, Kansai Medical University Masaaki Paku Department of Orthopaedic Surgery, Osaka Saiseikai Izuo Hospital Takeshi Tajima Department of Orthopaedic Surgery, Meisei Hospital Masaya Nakamura Department of Orthopaedic Surgery, McSYL Tatsumi Hospital Hirokazu Iida Department of Orthopaedic Surgery, Kansai Medical University Takanori Saito Department of Orthopaedic Surgery, Kansai Medical University Original Article 10.18926/AMO/59954 We retrospectively evaluated the cases of 169 hip fracture patients, their previous fractures, and the contralateral hip joint’s morphology. A history of contralateral hip fracture was present in 23 patients (Contra group). The other patients had a unilateral hip fracture: a trochanteric fracture (Troch group, n=73) or a femoral neck fracture (Neck group, n=73). In the Troch and Neck groups, we used anteroposterior and cross-table axialview radiographs of the contralateral hip to evaluate the proximal femur’s anatomy. In the Contra group, the concordance rate between the first and second types of hip fracture was 65.2%, and the second hip fracture’s morphology indicated that the trochanteric fracture had a cam deformity in terms of the femoral head-neck ratio. The average alpha angle and femoral head-neck offset in the Troch group were significantly larger than those in the Neck group. In the Neck group, pistol-grip deformities of Arbeitsgemeinschaft für Osteosynthesefragen types B1 (subcapital), B2 (transcervical), and B3 (displaced) were observed in 42.1%, 75%, and 6% of cases, respectively. There was a smaller alpha angle and a larger femoral head-neck offset in the contralateral hip of femoral neck fractures; thus, the “cam deformity” may protect against femoral neck fractures. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2020 Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer EN Shuichi Sakamoto 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 74 2 2020 Mucinous Carcinoma of the Breast: Clinicopathological Features and Long-term Prognosis in Comparison with Invasive Ductal Cancer; A Single Hospital’s 30+-Year Experience 137 143 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Yasuhisa Yamamoto Department of Surgery, Oomoto Hospital Kunihiko Sakai Department of Surgery, Oomoto Hospital Tatuo Sho Department of Surgery, Oomoto Hospital Kiyohiro Ishihara Department of Surgery, Oomoto Hospital Shigeki Murakami Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Original Article 10.18926/AMO/58272 Mucinous carcinoma (MC) of the breast is a rare and special type of malignancy, with a substantial amount of extracellular mucin. We compared the clinicopathological features and the long-term survival of MC patients with those of invasive ductal carcinoma-no special type (IDC-NST) patients, and we examined prognostic factors of MC. A total of 116 patients with mucinous carcinoma and 3,258 patients with IDC-NST who underwent surgery at our hospital (1977-2008) were enrolled. The 10-year overall survival rate and breast cancer-specific survival rate (BSS) of the MC patients (88.3%, 93.7%) were both significantly higher than those of IDC-NST patients (81.6%, 85.0%) (p=0.015, p=0.005, respectively). A Cox regression analysis demonstrated that MC tended to be an independent prognostic factor (hazard ratio 0.44, p=0.098). The BSS of the MC patients with positive lymph node (LN) metastasis was significantly poorer than that of the patients without it, by univariate analysis (p=0.002). The tumor size in the MC patients with positive LN metastasis (mean 3.2 cm) was significantly larger than that in the patients without it (mean 1.9 cm) (p=0.0004). Although a Cox regression analysis revealed no independent factor, MC patients with positive LN metastasis should be treated for advanced invasive ductal breast cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Increased Plasma Levels of Platelet Factor 4 and β-thromboglobulin in Women with Recurrent Pregnancy Loss 115 122 EN Sayoko Kotani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiko Kamada Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Shimizu Okayama Rosai Hospital Ai Sakamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Yuji Hiramatsu Okayama City Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/58269 Thrombosis in decidual vessels is one of the mechanisms of pregnancy loss. However, few studies have assessed the relation between platelet activation, which is known to cause of thrombosis, and recurrent pregnancy loss (RPL). We investigated platelet activation in women with RPL compared to controls by measuring plasma levels of platelet factor 4 (PF4) and β-thromboglobulin (βTG), and assessed correlations between PF4/βTG and coagulative risk factors associated with RPL. The study group included 135 women who had experienced two or more consecutive pregnancy losses. The control group included 28 age-matched healthy women who had never experienced pregnancy loss. PF4 and βTG plasma levels were significantly higher in the women with RPL than controls (PF4: 14.0 [8.0-20.0] vs. 9.0 [6.0-12.0] ng/ml, p=0.043; βTG: 42.0 [24.3-59.8] vs. 31.5 [26.6-36.4] ng/ml, p=0.002). There was a significant association between βTG and anti-phosphatidylethanolamine antibody immunoglobulin M (aPE IgM) (p=0.048). Among the women with RPL, 18 of those who were positive for PF4 (45%) and 18 of those who were positive for βTG (37%) were negative for all known coagulative risk factors associated with RPL. Measurements of PF4 and βTG may be important because they help identify women who are at risk of RPL. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Risk of Gynecologic Cancer as Second versus First Primary Cancer in Japan 109 114 EN Chikako Ogawa Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nakamura Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Matsuoka Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Matsubara Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Haraga 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/58268 This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan–Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 25890042 23 2 2020 PLOD2 is essential to functional activation of integrin β1 for invasion/metastasis in head and neck squamous cell carcinomas. 100850 EN Yushi Ueki Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Ken Saito Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Hidekazu Iioka Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Izumi Sakamoto ACROSCALE Inc. Yasuhiro Kanda Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Arata Horii Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences Eisaku Kondo Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 3 2019 Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL) 146 149 EN Namiko Matsumoto 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 Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maiko Sakamoto Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eisei Kondou Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rei Shibata Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 An Adult Case of Nasal Chondromesenchymal Hamartoma: Imaging Characteristics Including Diffusion-Weighted Images 529 532 EN Takahiro Kitayama Department of Radiology, Kagawa Prefectural Central Hospital Shiro Akaki Department of Radiology, Kagawa Prefectural Central Hospital Kento Hisazumi Department of Radiology, Kagawa Prefectural Central Hospital Kotaro Yoshio Department of Radiology, Kagawa Prefectural Central Hospital Daisaku Inoue Department of Radiology, Kagawa Prefectural Central Hospital Nobuhisa Tajiri Department of Radiology, Kagawa Prefectural Central Hospital Tsuyoki Shiode Department of Radiology, Kagawa Prefectural Central Hospital Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital Kengo Kanai Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital Yuji Hirata Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital Case Report 10.18926/AMO/57718 Nasal chondromesenchymal hamartoma (NCMH), a rare, benign, nasal cavity tumor, typically occurs in children. Differential diagnosis is difficult because NCMH often presents with non-specific findings, including cystic components and invasion of the surrounding area on T2-weighted magnetic resonance images. Here, we present a rare adult case of NCMH, with no clear hyperintensity on diffusion-weighted images (DWI), and bone remodeling on the tumor margins on computed tomography. To the best of our knowledge, this is the first report of DWI on NCMH, and these findings, which suggest benign disease, may be useful in diagnosing NCMH. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 6 2019 Correlations between Depressive Condition and Gastroesophageal Reflux Symptoms in Patients Visiting a Department of General Medicine 479 486 EN Yu Suganami Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Oka 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 Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Hamahara 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 Kazuya Kariyama 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/57711 To clarify the potential relevance of patients’ chief complaints at a general medicine department to their self-rating depression scale (SDS) and frequency scale for symptoms of gastroesophageal reflux disease (GERD) (FSSG) scores, we analyzed data of 478 patients who visited our general medicine department. The chief complaints (553 symptoms of 447 patients) were categorized into major symptom-based groups: respiratory (31%), circulatory (3%), gastrointestinal (GI) tract (26%), neurology (8%), orthopedic and skin (10%), and systemic (22%) symptoms. The SDS score tended to be higher in females and younger patients. The FSSG score did not differ by gender but was higher in younger patients. The patients receiving social welfare had higher SDS and FSSG scores. A close inter-relationship between the FSSG (including both degrees of reflux and dysmotility) and SDS was observed in all patients. Although the averages of the SDS and FSSG scores were not significantly different among the symptom-based categories, we observed significantly positive correlations between the FSSG and SDS in each category, suggesting that depressive status may be closely related to GERD-related symptoms regardless of the patients’ chief complaints. An initial checkup of patients’ psychological condition and/or GERD-like symptoms could help screen for latent disorders in outpatients with uncertain complaints. No potential conflict of interest relevant to this article was reported.

TAYLOR & FRANCIS Acta Medica Okayama 2162402X 8 12 2019 Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer e1671760 EN Shuichi Sakamoto 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 Kazuya Kuwada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atene Ito Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kajioka Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Tetsuya Kagawa 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 Satoru Kikuchi 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 Hiroshi Tazawa 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 A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 Risk Factors for Low Bone Mineral Density Determined in Patients in a General Practice Setting 403 411 EN Akemi Ando Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Mitsugi Honda Division of Radiology, Department of Medical Technology, Okayama University Hospital Yoshihisa Hanayama 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 Mikako Obika 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 Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/57370 Osteoporosis increases the risk of bone fractures. It is diagnosed based on an individual’s bone mineral density (BMD) or a fracture without trauma. BMD is usually measured by the dual energy X-ray absorptiometry (DXA) method. Here we investigated factors for the earliest possible prediction of decreased BMD by examining the relationships between patients’ BMD values and changes in the patients’ physical and laboratory values. We retrospectively reviewed the medical records of 149 patients who visited our department in 2014-2015 for a variety of reasons and underwent an area BMD examination by DXA. We analyzed the relationships between decreasing BMD and the patients’ gender, age, body mass index (BMI), medical background, hemoglobin, electrolytes, and thyroid function. Thirty-nine of the patients were diagnosed with osteoporosis based on their T-scores. An adjusted analysis showed that female gender, aging, and increased serum calcium level were significantly related to decreasing femoral BMD, whereas high BMI was associated with an increase in femoral BMD. Collectively the results indicate that for the early detection of low BMD, it is important for general-practice physicians to consider conducting a BMD checkup when treating female and elderly patients with a low BMI and/or elevated serum calcium level. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Psychiatry 189 195 EN Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ko Tsutsui Department of Neuropsychiatry, Akita University Graduate School of Medicine Takashi Kanbayashi Department of Neuropsychiatry, Akita University Graduate School of Medicine Keiko Tanaka Department of Animal Model Development, Brain Research Institute, Niigata University Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56860 Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently-discovered autoimmune disorder in which antibodies target NMDAR in the brain. The number of reported cases of anti-NMDAR encephalitis has increased rapidly. Anti-NMDAR encephalitis can be mistakenly diagnosed as psychiatric disorders because many patients present with prominent psychiatric symptoms and visit psychiatric institutions first. Thus, psychiatrists should cultivate a better understanding of anti-NMDAR encephalitis. In this review, we present the mechanisms, epidemiology, symptoms and clinical course, diagnostic tests, treatment and outcomes of patients with anti-NMDAR encephalitis. Furthermore, we discuss the diversity of clinical spectra of anti-NMDAR encephalitis, and demonstrate a differential diagnosis of psychiatric disease from the perspective of psychiatry. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Salvage Haploidentical Transplantation Using Low-dose ATG for Early Disease Relapse after First Allogeneic Transplantation: A Retrospective Single-center Review 161 171 EN Sachiyo Okamoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Maiko Sakamoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yoshiaki Usui Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yuki Fujiwara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Takumi Kondo Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Katsuma Tani Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Kyosuke Saeki Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yusuke Meguri Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Keiko Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceuticals Sciences Original Article 10.18926/AMO/56652 Second allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for patients who relapse after first allo-SCT. Human leukocyte antigen (HLA)-haploidentical related donors provide the broad opportunity to conduct second SCT at the appropriate time, but the efficacy of second SCT from haploidentical donors after relapse has not been established. We retrospectively analyzed the records of 33 patients who underwent second SCT. Twenty patients underwent haplo-SCT with low-dose antithymocyte globulin (ATG), and the other 13 patients underwent conventional- SCTs, including HLA-matched related peripheral blood, unrelated bone marrow or cord blood. Three years after the second SCT, the overall survival (OS) and progression-free survival (PFS) of all patients were 32.5% and 23.9%. Multivariate analyses indicated that non-complete response at second SCT, less than 1-year interval to relapse after first- SCT, and total score ≥ 3 on the hematopoietic cell transplantation-specific comorbidity index were significantly associated with a lower PFS rate. The haplo- and conventional- SCT groups showed equivalent results regarding OS, PFS, cumulative incidences of relapse, non-relapse mortality and graft-versus-host disease. The neutropenic period after transplantation was significantly shorter in haplo- SCT than conventional- SCT (10.5 days vs. 16 days, p=0.001). Our analysis revealed that haplo-SCT could be an alternative therapeutic option for relapsed patients after first SCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Clinical Characteristics of Severe Refractory Asthma Associated with the Effectiveness of Bronchial Thermoplasty 155 160 EN Daisuke Minami Department of Respiratory Medicine, Okayama Medical Center Hiroe Kayatani Department of Respiratory Medicine, Okayama Medical Center Ken Sato Department of Respiratory Medicine, Okayama Medical Center Keiichi Fujiwara Department of Respiratory Medicine, Okayama Medical Center Takuo Shibayama Department of Respiratory Medicine, Okayama Medical Center Toshiro Yonei Department of Respiratory Medicine, Okayama Medical Center Toshio Sato Department of Respiratory Medicine, Okayama Medical Center Original Article 10.18926/AMO/56651 We investigated the clinical characteristics of refractory asthma associated with the effectiveness of bronchial thermoplasty (BT). We retrospectively evaluated data from 10 patients who underwent BT between June 2016 and December 2017 at Okayama Medical Center. The following were measured before and 6 months post-BT: forced expiratory volume in 1.0 s (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) level, blood eosinophil counts (Eosi), Asthma Quality of Life Questionnaire (AQLQ) score, and preventive medication use. At baseline, the mean post-bronchodilator FEV1 was 80.9% of the predicted value (range 45.6-115.7%). All patients were being treated with moderate- or high-dose inhaled corticosteroids and long-acting β2 agonists. The AQLQ improved from 4.26±1.67 at baseline to 5.59±0.94 at 6 months post-BT (p<0.05). The %FEV1, FeNO, IgE, and Eosi did not change significantly between baseline and 6 months post-BT. No severe complications were reported. BT was effective for non-allergic and non-eosinophilic in 3 patients, and allergic or eosinophilic in 4 patients. Their AQLQ improved by > 0.5 points post-BT. For both allergic and eosinophilic asthmatics following mepolizumab, BT was not useful. BT was effective for non-allergic and non-eosinophilic or allergic asthmatics, but insufficient for both allergic and eosinophilic following mepolizumab. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Unintentional Injury Deaths among Children: A Descriptive Study Using Medico-legal Documents in Okayama Prefecture, Japan (2001−2015) 117 125 EN Yukie Yamasaki Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanako Tamiya Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Hideki Yamamoto Graduate School of Public Health, Teikyo University Satoru Miyaishi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56647 According to the World Health Organization’s World Report, approx. 950,000 children and young people < 18 years old die from an injury each year, and unintentional injury deaths account for a large portion of these cases. Here we used medico-legal documents to epidemiologically analyze the cases of unintentional injury deaths among children < 5 years old in Okayama Prefecture, Japan from 2001 to 2015. Age, sex, manner/cause of death, and various circumstances of the incident were investigated. There were 73 unintentional injury deaths during the study period. Drowning (n=29), suffocation (n=24), and transport accidents (n=13) were the major categories of unintentional injury deaths. Twenty-two cases (30.1%) were autopsied. Differences in the characteristics of the unintentional injury deaths by age were observed. Information which cannot be obtained from Vital Statistics was available from medico-legal documents, and detailed characteristics of unintentional injury deaths among children < 5 years old were elucidated. Investigating medico-legal information is one of the meaningful measures for the prevention of unintentional injury deaths among children in Japan. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 130 3 2018 平成29年度岡山医学会賞 脳神経研究奨励賞（新見賞） 109 111 EN Hiroshi Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 9 2019 「心のコミュニケーション」に関する道徳性の考察 : 教員養成課程におけるプレゼンテーションソフト活用会話形態が大学生に及ぼす道徳性の効果 85 98 EN Kiyomi Sakamoto Kiyokazu Sakuda Yoshikazu Nakayama 10.18926/CTED/56543 今日の教員への課題を取り上げ、意思疎通のあるコミュニケーションを導入した教員養成課程の必要性を検討した。なお、大学3年生(男性：10名、女性：15名)を対象として4種類の会話形態を行い、最も意思の疎通を感じ取ることのできるコミュニケーションが推認された。さらに、教職を目指す大学生を対象にして、プレゼンテーションソフトを活用した異コミュニケーションを行い、将来自分たちのえがいている教師像を目標として実施することにより、教員を志としての道徳観を抱くことが明確化された。そして、本研究における結果からこの会話形態により、道徳教育をはじめとする授業等を含めた学校教育活動全体に関わり、意思疎通による道徳性を高める効果が予測された。また、これからの倫理観と道徳観を培うための教員養成課程の在り方について明らかとした。 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Predictive Factors for Successful Vaccination Against Hepatitis B Surface Antigen in Patients Who Have Undergone Orthotopic Liver Transplantation 41 50 EN Ailee Ikeda 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 Tetsuya Yasunaka 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 Hideki Onishi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fusao Ikeda 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 Kazuhiro Yoshida Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Kuise Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Nobuoka Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Transplant and Surgical 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/56457 Post-orthotopic liver transplantation (OLT) hepatitis B recurrence is well-controlled with a nucleos(t)ide analogue and hepatitis B immunoglobulin (HBIG) combination, but the high cost and the potential risk of unknown infection associated with HBIG remain unresolved issues. Low-cost recombinant hepatitis B virus (HBV) vaccine administration is a potential solution to these problems. We retrospectively analyzed the rate and predictive factors of HBV vaccine success in 49 post-OLT patients: liver cirrhosis-type B (LC-B), n=28 patients; acute liver failure-type B (ALF-B), n=8; and non-HBV-related end-stage liver disease (non-B ESLD) who received a liver from anti-hepatitis B core antibody-positive donors, n=13. A positive anti-hepatitis B surface antibody response was achieved in 29% (8/28) of the LC-B group, 88% (7/8) of the ALF-B group, and 44% (4/9) of the adult non-B ESLD group. All four non-B ESLD infants showed vaccine success. The predictive factors for a good response in LC-B were young age, marital donor, and high donor age. ALF-B and non-B ESLD infants are thus good vaccination candidates. LC-B patients with marital donors are also good candidates, perhaps because the donated liver maintains an efficient immune memory to HBV, as the donors had already been infected in adulthood and showed adequate anti-HBV immune responses. No potential conflict of interest relevant to this article was reported.

Springer Nature Publishing AG Acta Medica Okayama 20550278 4 2018 Organelle DNA degradation contributes to the efficient use of phosphate in seed plants 1044 1055 EN Tsuneaki Takami Institute of Plant Science and Resources, Okayama University Norikazu Ohnishi Institute of Plant Science and Resources, Okayama University Yuko Kurita Faculty of Agriculture, Ryukoku University Shoko Iwamura Department of Biology, Graduate School of Science, Kobe University Miwa Ohnishi Department of Biology, Graduate School of Science, Kobe University Makoto Kusaba Graduate School of Science, Hiroshima University Tetsuro Mimura Department of Biology, Graduate School of Science, Kobe University Wataru Sakamoto Institute of Plant Science and Resources, Okayama University Mitochondria and chloroplasts (plastids) both harbour extranuclear DNA that originates from the ancestral endosymbiotic bacteria. These organelle DNAs (orgDNAs) encode limited genetic information but are highly abundant, with multiple copies in vegetative tissues, such as mature leaves. Abundant orgDNA constitutes a substantial pool of organic phosphate along with RNA in chloroplasts, which could potentially contribute to phosphate recycling when it is degraded and relocated. However, whether orgDNA is degraded nucleolytically in leaves remains unclear. In this study, we revealed the prevailing mechanism in which organelle exonuclease DPD1 degrades abundant orgDNA during leaf senescence. The DPD1 degradation system is conserved in seed plants and, more remarkably, we found that it was correlated with the efficient use of phosphate when plants were exposed to nutrient-deficient conditions. The loss of DPD1 compromised both the relocation of phosphorus to upper tissues and the response to phosphate starvation, resulting in reduced plant fitness. Our findings highlighted that DNA is also an internal phosphate-rich reservoir retained in organelles since their endosymbiotic origin. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 11 9 2016 A Novel High-Throughput 3D Screening System for EMT Inhibitors: A Pilot Screening Discovered the EMT Inhibitory Activity of CDK2 Inhibitor SU9516 e0162394 EN Kazuya Arai SCIVAX Life Sciences, Inc. Takanori Eguchi Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences M. Mamunur Rahman SCIVAX USA, Inc. Ruriko Sakamoto SCIVAX Life Sciences, Inc. Norio Masuda SCIVAX Life Sciences, Inc. Tetsuya Nakatsura Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Stuart K. Calderwood Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Ken-ichi Kozaki Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Itoh SCIVAX Life Sciences, Inc. Epithelial-mesenchymal transition (EMT) is a crucial pathological event in cancer, particularly in tumor cell budding and metastasis. Therefore, control of EMT can represent a novel therapeutic strategy in cancer. Here, we introduce an innovative three-dimensional (3D) high-throughput screening (HTS) system that leads to an identification of EMT inhibitors. For the establishment of the novel 3D-HTS system, we chose NanoCulture Plates (NCP) that provided a gel-free micro-patterned scaffold for cells and were independent of other spheroid formation systems using soft-agar. In the NCP-based 3D cell culture system, A549 lung cancer cells migrated, gathered, and then formed multiple spheroids within 7 days. Live cell imaging experiments showed that an established EMT-inducer TGF-β promoted peripheral cells around the core of spheroids to acquire mesenchymal spindle shapes, loss of intercellular adhesion, and migration from the spheroids. Along with such morphological change, EMT-related gene expression signatures were altered, particularly alteration of mRNA levels of ECAD/CDH1, NCAD/CDH2, VIM and ZEB1/TCF8. These EMT-related phenotypic changes were blocked by SB431542, a TGF-βreceptor I (TGFβR1) inhibitor. Inside of the spheroids were highly hypoxic; in contrast, spheroid-derived peripheral migrating cells were normoxic, revealed by visualization and quantification using Hypoxia Probe. Thus, TGF-β-triggered EMT caused spheroid hypoplasia and loss of hypoxia. Spheroid EMT inhibitory (SEMTIN) activity of SB431542 was calculated from fluorescence intensities of the Hypoxia Probe, and then was utilized in a drug screening of EMT-inhibitory small molecule compounds. In a pilot screening, 9 of 1,330 compounds were above the thresholds of the SEMTIN activity and cell viability. Finally, two compounds SB-525334 and SU9516 showed SEMTIN activities in a dose dependent manner. SB-525334 was a known TGFβR1 inhibitor. SU9516 was a cyclin-dependent kinase 2 (CDK2) inhibitor, which we showed also had an EMT-inhibitory activity. The half maximal inhibitory concentration (IC50) of SB-525334 and SU9516 were 0.31 μM and 1.21 μM, respectively, while IC50 of SB431542 was 2.38 μM. Taken together, it was shown that this 3D NCP-based HTS system was useful for screening of EMT-regulatory drugs. No potential conflict of interest relevant to this article was reported.

岡山実験動物研究会 Acta Medica Okayama 34 2018 無腸動物Praesagittifera naikaiensis における細胞骨格要素 21 27 EN Risa Ikeda Graduate School of Education, Okayama University Chiho Fujiwara Graduate School of Education, Okayama University Mayuko Hamada Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Noboru Saito Graduate School of Environmental and Life Science, Okayama University Motonori Ando Graduate School of Education, Okayama University Acoel flatworms can move in a variety of ways such as muscular and ciliary movements via cytoskeletal elements and their neural regulations. However, those locomotive mechanisms have not yet been fully elucidated. In this study, we examined the distribution of cytoskeletal elements including filamentous actin (F-actin) and tubulin, and the neuroanatomical organization in an acoelomorph worm, Praesagittifera naikaiensis (P. naikaiensis). Video microscopy revealed the elongation/contraction and the bending/rotation processes, and the ciliary gliding movement of P. naikaiensis. Histochemical and morphological analysis demonstrated that F-actin networks of inner longitudinal and outer circular muscle fibers were positioned along the entire surface of the body, and that the average distance between the circular muscle fibers in the contracted organism was decreased in the anterior region compared with that in the elongated organism. Electron microscopy showed dense bodies on the muscle cells of P. naikaiensis, which indicates that those muscle cells have the appearance of vertebrate smooth muscle cells. Immunohistochemical analysis revealed that -tubulin-positive signals on the ciliary microtubules had close contact with the F-actin network, and that neurite bundles labelled with anti dSap47 antibody as a neuronal marker run along the anterior-posterior body axis. These results indicate that the well-organized cytoskeletal elements and their neural control systems are preserved in P. naikaiensis, and that their mechanisms involved in those regulation systems are similar to those vertebrate systems. Further studies are needed to clarify the physiological mechanisms underlying the muscular and ciliary movements in P. naikaiensis. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2018 Slow Fetal Heart Rate before Miscarriage in the Early First Trimester Predicts Fetal Aneuploidy in Women with Recurrent Pregnancy Loss EN Ai Sakamoto 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 72 2 2018 Current Multidisciplinary Approach to Fertility Preservation for Breast Cancer Patients 137 142 EN Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Ai Sakamoto Department of Obstetrics and Gynecology, Okayama University Hospital Yuko Tsuyumu Department of Nursing, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Minami Hatono Department of Breast and Endocrine Surgery, Okayama University Hospital Mariko Kochi Department of Breast and Endocrine Surgery, Okayama University Hospital Kengo Kawada Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Hirokuni Ikeda Department of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrine Surgery, Okayama University Hospital Junji Matsuoka Department of Palliative and Supportive Medicine, Okayama University Hospital Mikiya Nakatsuka Department of Obstetrics and Gynecology, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/55854 Adverse effects on fertility are a significant problem for premenopausal breast cancer patients. Since April 2009, we have been referring young patients for fertility counseling provided by a multidisciplinary team. Here we evaluated the efficacy and safety of our current fertility preservation approach. We retrospectively analyzed the cases of 277 patients < 45 years old at diagnosis, which was made between 2009 and 2016. Seventy-two (26%) patients received fertility counseling. Seventeen (6%) of the 277 patients decided to preserve their fertility before starting adjuvant systemic therapy. Six (35%) patients underwent oocyte cryopreservation, and 11 (65%) married patients opted for embryo cryopreservation. There were no pregnancies among the patients undergoing oocyte cryopreservation, whereas 3 (27%) of the patients who opted for embryo cryopreservation became pregnant. Two (12%) patients stopped endocrine therapy after 2 years in an effort to become pregnant, but their breast cancers recurred. Though the problem of fertility loss for breast cancer patients is important and we should assess the infertility risk for all patients, we should also consider the prognosis. In June 2016, we launched a prospective multicenter cohort study to evaluate the efficacy and safety of fertility preservation in greater detail. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 1 2018 Slow Fetal Heart Rate before Miscarriage in the Early First Trimester Predicts Fetal Aneuploidy in Women with Recurrent Pregnancy Loss 61 66 EN Ai Sakamoto Department of Obstetrics and Gynecology, Okayama University Graduate Schools of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiko Kamada Department of Obstetrics and Gynecology, Okayama University Graduate Schools of Medicine, Dentistry and Pharmaceutical Sciences Kotaro Kubo Department of Obstetrics and Gynecology, Okayama University Graduate Schools of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of Obstetrics and Gynecology, Okayama University Graduate Schools of Medicine, Dentistry and Pharmaceutical Sciences Sayoko Kotani Department of Obstetrics and Gynecology, Okayama University Graduate Schools of Medicine, Dentistry and Pharmaceutical Sciences Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Yuji Hiramatsu Department of Obstetrics and Gynecology, Okayama University Graduate Schools of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/55664 Establishing whether miscarriages result from fetal aneuploidy or other factors is important for treating recurrent pregnancy loss. We examined the relationship between fetal heart rate (FHR) before miscarriage in the early first trimester and fetal karyotype, analyzing 223 pregnant women with recurrent pregnancy loss. Among the pregnancies, 110 resulted in live births regarded as normal karyotype (the Norm-group). The other 113 pregnancies ended in miscarriage, and we categorized them into groups based on fetal karyotype, determined by chorionic villus sampling: the Misc-NK (normal karyotype) group, n=35 euploid cases; the Misc-CA1 (chromosomal abnormality) group, n=18 cases of aneuploidy with trisomies 13/18/21, Turner’s syndrome, or Klinefelter’s syndrome; and the Misc-CA2 subgroup, n=60 cases of other aneuploidies excluding those in the Misc-CA1 group. We compared the groups’ regression line slopes and intercepts for FHR by an analysis of covariance. The FHRs of the Norm, Misc-NK and Misc-CA1 groups increased from 36 to 49 days after fertilization, but did not significantly differ across these groups. The Misc-CA2 group’s FHR did not increase and significantly differed from the other three groups (p<0.01). These results suggest that the absence of an increase in FHR in early pregnancy may indicate the presence of chromosomal abnormalities causing miscarriage. No potential conflict of interest relevant to this article was reported.

Japanese Society of Plant Physiologists Acta Medica Okayama 0032-0781 55 7 2014 Quality control of photosystem II: direct imaging of the changes in the thylakoid structure and distribution of FtsH proteases in spinach chloroplasts under light stress 1255 1265 EN Miho Yoshioka-Nishimura Graduate School of Natural Science and Technology, Okayama University Daisuke Nanba Graduate School of Natural Science and Technology, Okayama University Takashi Takaki Techinical support center, JEOL Chikako Ohba Graduate School of Natural Science and Technology, Okayama University Nodoka Tsumura Graduate School of Natural Science and Technology, Okayama University Noriko Morita Graduate School of Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute, Okayama University Kazuyoshi Murata National Institute for Physiological Sciences Yasusi Yamamoto Graduate School of Natural Science and Technology, Okayama University 　Under light stress, the reaction center-binding protein D1 of PSII is photo-oxidatively damaged and removed from PSII complexes by proteases located in the chloroplast. A protease considered to be responsible for degradation of the damaged D1 protein is the metalloprotease FtsH. We showed previously that the active hexameric FtsH protease is abundant at the grana margin and the grana end membranes, and this homo-complex removes the photodamaged D1 protein in the grana. Here, we showed a change in the distribution of FtsH in spinach thylakoids during excessive illumination by transmission electron microscopy (TEM) and immunogold labeling of FtsH. The change in distribution of the protease was accompanied by structural changes to the thylakoids, which we detected using spinach leaves by TEM after chemical fixation of the samples. Quantitative analyses showed several characteristic changes in the structure of the thylakoids, including shrinkage of the grana, outward bending of the marginal portions of the thylakoids and an increase in the height of the grana stacks under excessive illumination. The increase in the height of the grana stacks may include swelling of the thylakoids and an increase in the partition gaps between the thylakoids. These data strongly suggest that excessive illumination induces partial unstacking of the thylakoids, which enables FtsH to access easily the photodamaged D1 protein. Finally three-dimensional tomography of the grana was recorded to observe the effect of light stress on the overall structure of the thylakoids. No potential conflict of interest relevant to this article was reported.

Japanese Society of Plant Physiologists Acta Medica Okayama 0032-0781 57 8 2016 The SAC51 Family Plays a Central Role in Thermospermine Responses in Arabidopsis 1583 1592 EN Qingqing Cai Graduate School of Natural Science and Technology, Okayama University Hiroko Fukushima Graduate School of Natural Science and Technology, Okayama University Mai Yamamoto Graduate School of Natural Science and Technology, Okayama University Nami Ishii Graduate School of Natural Science and Technology, Okayama University Tomoaki Sakamoto Graduate School of Biological Sciences, Nara Institute of Science and Technology Tetsuya Kurata Graduate School of Biological Sciences, Nara Institute of Science and Technology Hiroyasu Motose Graduate School of Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Natural Science and Technology, Okayama University The acaulis5 (acl5) mutant of Arabidopsis thaliana is defective in the biosynthesis of thermospermine and shows a dwarf phenotype associated with excess xylem differentiation. SAC51 was identified from a dominant suppressor of acl5, sac51-d, and encodes a basic helix-loop-helix protein. The sac51-d mutant has a premature termination codon in an upstream open reading frame (uORF) that is conserved among all four members of the SAC51 family, SAC51 and SACL1-SACL3 This suggests that thermospermine cancels the inhibitory effect of the uORF in main ORF translation. Another suppressor, sac57-d, has a mutation in the conserved uORF of SACL3 To define further the function of the SAC51 family in the thermospermine response, we analyzed T-DNA insertion mutants of each gene. Although sacl1-1 may not be a null allele, the quadruple mutant showed a semi-dwarf phenotype but with an increased level of thermospermine and decreased sensitivity to exogenous thermospermine that normally represses xylem differentiation. The sac51-1 sacl3-1 double mutant was also insensitive to thermospermine. These results suggest that SAC51 and SACL3 play a key role in thermospermine-dependent negative control of thermospermine biosynthesis and xylem differentiation. Using 5' leader-GUS (β-glucuronidase) fusion constructs, however, we detected a significant enhancement of the GUS activity by thermospermine only in SAC51 and SACL1 constructs. Furthermore, while acl5-1 sac51-1 showed the acl5 dwarf phenotype, acl5-1 sacl3-1 exhibited an extremely tiny-plant phenotype. These results suggest a complex regulatory network for the thermospermine response in which SAC51 and SACL3 function in parallel pathways. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 2 2017 家族性大腸腺腫症術後20年後に小腸癌を発症した1例 111 114 EN Yuusaku Sugihara Department of Gastroenterology and Hepatology, Okayama University Hospital Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Hospital Keita Harada Department of Gastroenterological Surgery, Okayama University Hospital Shiho Takashima Department of Gastroenterology and Hepatology, Okayama University Hospital Daisuke Takei Department of Gastroenterological Surgery, Okayama University Hospital Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Masahiro Takahara Department of Gastroenterology and Hepatology, Okayama University Hospital Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Hospital Yoshiko Mori Division of Endoscopy, Okayama University Hospital Hiroyuki Kishimoto Division of Endoscopy, Okayama University Hospital Takeshi Nagasaka Division of Endoscopy, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Hospital A 58-year-old Japanese man visited a local clinic for the evaluation of a stomachache. He was diagnosed with intestinal obstruction. His medical history included a proctocolectomy at the age of 38 years, due to familial adenomatous polyposis (FAP). He was referred to our institution, where he underwent a computed tomography examination and endoscopy of the small intestine. The pathological diagnosis was adenocarcinoma. No invasive or metastatic lesions were observed. Therefore, partial resection of the ileum with lymphadenectomy and reconstruction of the ileostomy were performed. Pathological examination revealed that the tumor was type 2, pT3 (SS) , pN1, pPM0, pDM0, pRM0, INFb, ly1, v1, pEX0, PN0. Twenty-nine days after the surgery, the patient was diagnosed with lung metastasis and he underwent lung radiofrequency ablation. We suggest that long-term follow-up is necessary for patients after surgery for FAP, because of the risk of malignant disease developing in other organs. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0165-1781 216 2 2014 Four polymorphisms of the pericentriolar material 1 (PCM1) gene are not associated with schizophrenia in a Japanese population 288 289 EN Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Kodama Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ujike Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Uchitomi Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.