Japanese Circulation Society Acta Medica Okayama 1346-9843 89 6 2025 Clinical Impact of Genetic Testing for Long QT Syndrome　― Evidence From a Nationwide LQTS Registry in Japan ― 835 844 EN Takeshi Aiba Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Seiko Ohno Medical Genome Center, National Cerebral and Cardiovascular Center (NCVC) Misa Takegami Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center (NCVC) Yoshiaki Kato Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center (NCVC) Heima Sakaguchi Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center (NCVC) Keiko Shimamoto Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Keiko Sonoda Medical Genome Center, National Cerebral and Cardiovascular Center (NCVC) Kazufumi Ida Division of Counseling for Medical Genetics, National Cerebral and Cardiovascular Center (NCVC) Naokata Sumitomo Department of Pediatric Cardiology, Saitama Medical University International Medical Center Taisuke Nabeshima Department of Pediatric Cardiology, Saitama Medical University International Medical Center Takashi Murakami Department of Child Health, Institution of Medicine, University of Tsukuba Yumiko Ninomiya Department of Pediatrics, National Hospital Organization Kagoshima Medical Center Koichi Kato Department of Cardiovascular Medicine, Shiga University of Medical Science Megumi Fukuyama Department of Cardiovascular Medicine, Shiga University of Medical Science Takeru Makiyama Department of Cardiology, Kyoto University Kenshi Hayashi Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences Kunio Ohta Department of Medical Education, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University Graduate School of Medical Sciences Hiroshi Morita Okayama University Graduate School of Medicine Tadashi Nakajima Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine Yoshiaki Kaneko Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine Nobue Yagihara Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Sou Otsuki Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences Tomoki Kosho Department of Medical Genetics, Shinshu University School of Medicine Yoko Yoshida Osaka City General Hospital Motoki Takamuro Hokkaido Children’s Hospital Michihiko Ueno Department of Pediatrics, Teine-Keijinkai Hospital Tatsunori Takahashi Department of Pediatrics, Yamagata University Faculty of Medicine Yasuya Inden Department of Cardiology, Nagoya University Graduate School of Medicine Yasunobu Hayabuchi Department of Pediatrics, Tokushima University Shota Muraji Fukuoka Children’s Hospital Shigeo Watanabe Yokohama City University Kunihiro Nishimura Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center (NCVC) Yoshihiro Asano Department of Genomic Medicine, National Cerebral and Cardiovascular Center (NCVC) Hitoshi Horigome Department of Child Health, Institution of Medicine, University of Tsukuba Masao Yoshinaga Department of Pediatrics, National Hospital Organization Kagoshima Medical Center Minoru Horie Department of Cardiovascular Medicine, Shiga University of Medical Science Wataru Shimizu Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Kengo Kusano Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center (NCVC) Background: Genetic testing for long QT syndrome (LQTS) is useful for diagnosis, risk stratification, and therapeutic strategies. This study investigated the clinical impact of genetic testing for LQTS patients.<br> Methods and Results: Total 3,851 patients (proband: 2,316 [60%]; female: 2,283 [59%]; median age: 14 years [interquartile range 9–36 years]) diagnosed with LQTS (LQTS score ≥3.5, QTc ≥500 ms, pathogenic variants in LQTS-associated genes, or unexplored syncope with QTc 480–499 ms) were enrolled in this study. Of these patients, 1,146 (29.8%) experienced syncope and 322 (8.5%) experienced ventricular fibrillation (VF) or cardiopulmonary arrest (CPA) at ≤70 years of age. Genetic testing using a next-generation sequencing panel and/or Sanger sequencing was performed for 3,770 (98%) patients, genotype was then identified in the following LQTS-associated genes: KCNQ1 (45%), KCNH2 (34%), SCN5A (8%), KCNE1 (0.1%), KCNE2 (0.03%), KCNJ2 (2.7%), CACNA1C (1.2%), and CALM1,2 (0.3%). Forty-seven (1.2%) patients had double or compound heterozygous variants in LQTS-associated genes, whereas the genotype remained unknown in 220 (5.8%) patients. When comparing phenotype with genotype, QTc was significantly longer in CALM1,2 patients than in others except for CACNA1C, whereas QTc was almost normal in KCNJ2 patients. The incidence of the first cardiac event (syncope, VF/CPA) differed among the genotypes, and prognosis was significantly worse for CALM1,2 patients.<br> Conclusions: Comprehensive genetic testing, including non-major LQTS genes, is important for diagnosis and risk stratification of LQTS. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 6 2026 Association between venous access-site closure device use and postoperative nausea and vomiting after atrial fibrillation ablation under propofol sedation: a single-centre retrospective observational study in Okayama, Japan e117719 EN Haruna Sakanoue Department of Nursing, Okayama Heart Clinic Hirosuke Yamaji Heart Rhythm Centre, Okayama Heart Clinic Sayaka Okamoto Department of Nursing, Okayama Heart Clinic Kumi Okano Department of Nursing, Okayama Heart Clinic Yuka Fujita Department of Nursing, Okayama Heart Clinic Shunichi Higashiya Heart Rhythm Centre, Okayama Heart Clinic Takashia Murakami Heart Rhythm Centre, Okayama Heart Clinic Satoshi Hirohata Graduate School of Health Sciences, Department of Medical Technology, Okayama University Shozo Kusachi Heart Rhythm Centre, Okayama Heart Clinic Objectives To examine whether the use of a venous access-site closure device is associated with the occurrence of postoperative nausea and vomiting (PONV) after atrial fibrillation (AF) ablation under propofol sedation.<br> Design Observational study.<br> Setting A single-centre retrospective observational study in Okayama, Japan.<br> Participants We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303).<br> Interventions Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis.<br> Primary outcome measure The primary outcome was the occurrence of PONV following AF ablation.<br> Results All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference −14.7 hours, 95% CI −15.2 to −14.0).<br> PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of −3.2% (95% CI −6.0% to −0.5%).<br> In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV.<br> Conclusions In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 19 2025 Chronic fluoxetine modulates perineuronal nets and inhibitory neuronal function in relation to behavioral outcomes 781 791 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Chronic fluoxetine administration has been reported to enhance neural plasticity in the adult brain, but the underlying structural correlates remain incompletely understood. In particular, the impact of fluoxetine on aggrecan-positive perineuronal nets (PNNs)—critical regulators of plasticity—is largely unknown. We investigated whether chronic fluoxetine treatment (20 mg/kg/day, i.p., 21 days) alters behavior and PNN expression in adult male C57BL/6 N mice. Behavioral assessments included grip strength, hot plate, light/dark transition, elevated plus-maze, open field, Y-maze, social interaction, tail suspension, Porsolt forced swim, and passive avoidance tests. To evaluate structural plasticity, we performed immunohistochemical analyses of parvalbumin (PV)-positive neurons and PNNs using aggrecan-specific antibodies (Cat-315, AB1031) in the primary somatosensory cortex and hippocampus. Fluoxetine-treated mice exhibited increased exploration and reduced anxiety-like behavior in light/dark transition and elevated plus-maze tests, with no significant changes in grip strength or nociception. They also showed increased locomotor activity (distance and entries) in the Y-maze, but did not significantly alter spontaneous alternation performance, and increased social interaction, the latter possibly reflecting abnormal social behavior. No significant differences were observed in depression-like behavior as assessed by tail suspension and forced swim tests. Passive avoidance performance was impaired, suggesting a decline in cognitive function. Immunohistochemical analysis revealed a significant reduction in aggrecan-positive PNN density, particularly in layer 4 of the primary somatosensory cortex and in the CA1 and CA3 regions of the hippocampus. Our results indicate that chronic fluoxetine administration induces behavioral and structural changes indicative of reactivated neuroplasticity. Importantly, these changes are associated with a region- and layer-specific reduction of aggrecan-positive PNNs, underscoring their critical role in modulating adult cortical plasticity. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 14 9 2026 Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivity e0086926 EN Hironobu Murakami School of Veterinary Medicine, Azabu University Reiichiro Sato Graduate School of Medicine and Veterinary Medicine, University of Miyazaki Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Sogawa School of Life and EnvironmentaScience, Azabu University Hiroho Ishida School of Veterinary Medicine, Azabu University Makoto Nagai School of Veterinary Medicine, Azabu University Bovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50–68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1473-0502 65 5 2026 Association of initial interface formation time with CD34+ collection efficiency in continuous mononuclear cell collection: A retrospective study 104504 EN Hiroyuki Murakami Department of Hematology, Okayama University Hospital Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Factors influencing CD34+ cell collection efficiency (CE) during peripheral blood stem cell harvesting have been investigated; however, the impact of procedural management remains unclear. In continuous mononuclear cell (CMNC) collection, a stable cell–plasma interface (IF) is formed through channel priming, initial IF establishment, and mononuclear cell (MNC) collection. Although IF instability is known to impair CE, the adequacy of initial IF formation has not been examined as an independent factor. Therefore, we focused on the time required for initial IF formation and its association with CE.<br> Methods: We retrospectively analyzed 291 Spectra Optia CMNC procedures (52 autologous and 239 allogeneic) performed between 2016 and 2025. Initial interface formation time (IFT) was defined as the interval from the start of the procedure to transition to MNC collection. CE2 was defined as the ratio of collected CD34+ cells to the product of pre-apheresis peripheral blood CD34+ cell concentration and processed blood volume. Results: CE2 was lower in autologous than in allogeneic collections (41.3% vs. 59.2%) and was associated with longer IFT (median, 18 vs. 15 min). CE2 correlated with white blood cell count (r = −0.24), hematocrit (r = 0.36), and IFT (r = −0.23; all p < 0.001). In multivariable analysis, these factors remained independently associated with CE2, and IFT was inversely correlated with hematocrit (r = −0.44, p < 0.001).<br> Conclusion: IFT is independently associated with CE2 and provides insight into the early dynamics of IF formation during leukapheresis, highlighting an underexplored procedural aspect of CE. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 20 2026 Behavioral effects of a chronic envy-like stress paradigm in mice using an adjacent cage model 148 159 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yoshihiro Tanaka Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Background: Social comparison and envy are significant psychosocial stressors in humans and are known to be involved in the onset and persistence of psychiatric disorders. However, animal models capable of experimentally reproducing the effects of indirect social comparison without physical contact are limited. In this study, we used a newly developed "adjacent-cage paradigm" to investigate whether chronic vicarious exposure to conspecifics in different environments induces envy-like stress in mice.<br> Methods: Male C57BL/6 N mice served as observers, while demonstrator mice were assigned to one of four conditions: (1) an environment enriched with objects, (2) an igloo, (3) a tube, or (4) social isolation. Observers were continuously exposed to these adjacent cages for 21 days. Subsequently, a comprehensive battery of behavioral tests was conducted to assess general health, anxiety-like behavior, spatial memory, social behavior, and depression-like behavior.<br> Results: In the objects condition, a decrease in time spent in the light compartment of the light/dark box indicated an increase in anxiety-like behavior. In the isolation condition, the mean duration per social interaction was shortened, suggesting a qualitative change in social behavior. The igloo condition resulted in reduced immobility time in the forced swim test, suggesting a possible alteration in stress coping behavior. Furthermore, increased nociceptive sensitivity was observed in the hot plate test under both the objects and isolation conditions.<br> Conclusion: Although the envy-like stress paradigm did not affect many behavioral indices, it did cause condition-dependent and limited behavioral changes. This suggests that the paradigm may serve as a novel model for capturing psychological and context-dependent social stress, which differs from conventional physical stress models. Elucidating the neural basis of this paradigm is expected to contribute to the understanding of how social comparison affects mental health in modern society. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Adolescent envy-like social comparison stress induces HPA axis hypoactivity and anxiety in female mice: implications for somatic symptom disorder 15771 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yoshihiro Tanaka Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Adolescence is a critical developmental window marked by heightened neuroplasticity and maturation of the stress response system, conferring vulnerability to psychosocial stress. Chronic stress during this period increases the risk of anxiety and depressive disorders and may contribute to somatic symptom disorder (SSD), which is characterized by medically unexplained physical complaints and shows a striking female predominance. The impact of envy-like stress arising from social comparison, a pervasive psychosocial factor in modern society, remains poorly understood. Male and female C57BL/6N mice were exposed to chronic envy-like stress from postnatal day (P)21 to P52 by housing them adjacent to enriched cages, while control mice were housed without such exposure. From P52 onward, mice underwent behavioral testing of anxiety-like behavior, exploratory activity, social interaction, spatial working memory, motor coordination, nociception, and depression-like behavior. Serum corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured to assess hypothalamic–pituitary–adrenal (HPA) axis function. Envy-like stress induced sex-specific phenotypes. Male mice exhibited hyperactivity, reduced social interaction, and impaired spatial working memory. In contrast, female mice displayed robust increases in anxiety-like behavior, impaired motor coordination, and significant reductions in basal corticosterone and ACTH levels. Chronic envy-like stress during adolescence elicits distinct, sex-dependent behavioral and endocrine alterations. The phenotype observed in female mice—characterized by heightened anxiety and lower basal HPA axis hormone levels—shares some biological features with clinical observations in SSD. This model may serve as a starting point for elucidating the mechanisms linking psychosocial stress and somatic symptoms in a sex-dependent manner. 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 Post-weaning maternal presence exerts a protective effect against social isolation-induced behavioural alterations in mice 44248 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Parental “watchful presence” is considered an important factor influencing behavioural and emotional development in offspring across mammalian species, including humans. However, the effects of such parental presence remain insufficiently understood, even in human studies. In laboratory mice, offspring are typically weaned at approximately three weeks of age, leaving the impact of post-weaning maternal presence on behavioural development largely unexplored. This study aimed to investigate whether maternal presence in an adjacent cage after weaning can attenuate behavioural effects of social isolation stress in mice. Furthermore, we sought to assess whether this experimental paradigm could serve as a novel animal model for studying the effects of parental watchful presence, with potential relevance to human parent–child relationship research. Mouse pups were weaned at postnatal day 21 and housed either adjacent to their mother (maternal presence group) or without maternal presence (control group). The pups were subsequently housed either in groups with littermates or individually until eight weeks of age. After maturation, behavioural tests were conducted to assess locomotor activity, anxiety-like behaviour, social behaviour, and depression-like behaviour. In group-housed mice, maternal presence did not influence behavioural outcomes. However, in individually housed mice, maternal presence partially attenuated social isolation-induced behavioural alterations, suggesting a subtle protective effect, including hyperlocomotion, reduced anxiety-like behaviour, and abnormal social interactions. Our findings demonstrate that maternal presence during the post-weaning period can offer a protective effect against certain behavioural abnormalities induced by social isolation stress in mice.　This simple adjacent-cage paradigm provides a novel and practical model for elucidating the impact of parental watchful presence on behavioural and emotional development, offering insights relevant to the understanding of parent–child relationships in humans. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1471-2431 26 1 2026 Hypernatremia during the first week of life in very preterm infants and neurodevelopmental outcomes at 3 to 4 years of age: a cohort study 181 EN Michiko Murakami Division of Neonatology, NHO Okayama Medical Center Kei Tamai Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naomi Matsumoto Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihito Takeuchi Division of Neonatology, NHO Okayama Medical Center Makoto Nakamura Division of Neonatology, NHO Okayama Medical Center Takashi Yorifuji Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Misao Kageyama Division of Neonatology, NHO Okayama Medical Center Background Hypernatremia is a common electrolyte disorder in both term and preterm infants. Previous studies have suggested a correlation between hypernatremia and short-term complications in preterm infants, such as intraventricular hemorrhage and chronic lung disease. However, the relationship between hypernatremia and neurodevelopmental outcomes is less well understood. This study aimed to assess the association between hypernatremia during the first week of life and neurodevelopmental outcomes at 3–4 years of age in very preterm infants.<br> Methods This single-center, retrospective cohort study analyzed data from preterm infants born at less than 32 weeks of gestation between 2010 and 2020. Infants with peak whole blood sodium levels > 145 mEq/L during the first week of life were included in the hypernatremia group and those with ≤ 145 mEq/L in the non-hypernatremia group. The primary outcome was neurodevelopmental impairment (NDI) at 3–4 years of age, defined as developmental impairment (developmental quotient < 70), cerebral palsy, hearing impairment, or visual impairment. Secondary outcomes were the components of the primary outcome. We conducted Poisson regression analyses with robust variance, adjusting for perinatal confounders.<br> Results Of 272 infants with neurodevelopmental data, 82 and 190 infants were in the hypernatremia and non-hypernatremia groups, respectively. The median (interquartile range) gestational age and birth weight were 26.4 (25.1–28.0) and 28.7 (26.6–30.3) weeks and 860 (670–1062) and 997 (778–1264) g for infants in the hypernatremia and non-hypernatremia groups, respectively. Infants in the hypernatremia group had a greater incidence of NDI (29.3% vs. 14.7%, adjusted risk ratio [RR] 1.75, 95% CI 1.08–2.84) and cerebral palsy (8.5% vs. 1.6%, adjusted RR 5.5, 95% CI 1.72–17.63) than those in the non-hypernatremia group.<br> Conclusions Hypernatremia during the first week of life was associated with an increased risk of NDI at 3–4 years of age in very preterm infants. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1432-0851 75 3 2026 A real-world comparison of nivolumab plus cabozantinib and pembrolizumab plus lenvatinib focusing on safety outcomes in metastatic renal cell carcinoma: results from the JK-FOOT consortium 84 EN Takafumi Yanagisawa Department of Urology, The Jikei University School of Medicine Keiichiro Mori Department of Urology, The Jikei University School of Medicine Tatsushi Kawada Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Satoshi Katayama Department of Urology, Comprehensive Cancer Center, Medical University of Vienna Takuya Tsujino Department of Urology, Osaka Medical and Pharmaceutical University Ryoichi Maenosono Department of Urology, Osaka Medical and Pharmaceutical University Shingo Toyoda Department of Urology, Faculty of Medicine, Kindai University Takuhisa Nukaya Department of Urology, Fujita-Health University School of Medicine Hirofumi Morinaka Department of Urology, Kawasaki Medical School Keita Tamura Department of Urology, Hamamatsu Medical University Wataru Fukuokaya Department of Urology, The Jikei University School of Medicine Fumihiko Urabe Department of Urology, The Jikei University School of Medicine Masaya Murakami Department of Urology, The Jikei University School of Medicine Kensuke Bekku Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiyoshi Takahara Department of Urology, Fujita-Health University School of Medicine Kazutoshi Fujita Department of Urology, Faculty of Medicine, Kindai University Haruhito Azuma Department of Urology, Osaka Medical and Pharmaceutical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teruo Inamoto Department of Urology, Hamamatsu Medical University Kazumasa Komura Department of Urology, Kawasaki Medical School Takahiro Kimura Department of Urology, The Jikei University School of Medicine Purpose Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC.<br> Methods This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching.<br> Results Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5).<br> Conclusions Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations. 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 「新羅村落文書」に記された村の比定地 ―西原京所属の村（いわゆるＤ村）の検討― 40 53 EN Nana MURAKAMI Research Institute for the Dynamics of Civilizations, Okayama University 研究ノート (Research note) 10.18926/70053 The Silla Village Register is a fragmentary record from the Unified Silla period that details the economic conditions of villages under the jurisdiction of small capitals (小京) and local counties (郡 / 県). In analyzing this register, it is essential to consider the geographical conditions of the locations; however, the exact locations of the villages have long remained unidentified in previous studies. Therefore, this study builds on the readings proposed by Choi Kyŏng-sŏn ( 최 경 선 ) and examines official histories and geographical texts from the Chosŏn dynasty, as well as topographic maps from the early 20th century. As a result, this paper proposes a concrete candidate for the location of one of the four villages under the jurisdiction of Sŏwŏn-gyŏng (西原京), commonly referred to as Village D. It has been clarified that Village D can be read as " 西原京□椒子村" and it is highly likely to correspond to present-day Chojŏng-ri, Naesu-ŭp, Heungdeok-gu, Cheongju City (清州市清原区内秀邑椒井里). It was also found that Village D’s characteristic of having few rice paddies and a high proportion of upland field cultivation closely matches the actual local geographical conditions, which are characterized by limited water resources. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 2026 Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A EN Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children.<br> Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency.<br> Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117–302] vs. 157 min [range, 103–227], p = .02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, −55.6; 95% confidence interval, −106.2 to −5.04; p = .03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r = −.73, p = .0003).<br> Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. No potential conflict of interest relevant to this article was reported.

Japan Oil Chemists' Society Acta Medica Okayama 1345-8957 74 11 2025 Bioconversion and Metabolic Fate of the n-1 Polyunsaturated Fatty Acids, 6,9,12,15- Hexadecatetraenoic (C16:4 n-1) and 8,11,14,17- Octadecatetraenoic (C18:4 n-1) Acids, in HepG2 Cells 1023 1032 EN Koki Sugimoto Faculty of Food and Nutritional Sciences, Toyo University Hideto Nishiguchi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Ryota Hosomi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Toshifumi Tanizaki Bizen Chemical Co., Ltd. Tadahiro Tsushima Bizen Chemical Co., Ltd. Naomichi Baba Bizen Chemical Co., Ltd. Yoshihisa Misawa Bizen Chemical Co., Ltd. Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Murakami Department of Hygiene and Public Health, Kansai Medical University Seiji Kanda Department of Hygiene and Public Health, Kansai Medical University Kenji Fukunaga Faculty of Chemistry, Materials, and Bioengineering, Kansai University Fish oil contains not only major fatty acids with double bonds at the n-3, n-6, n-7, and n-9 positions but also those with a double bond at the n-1 position, such as 6,9,12,15-hexadecatetraenoic acid (C16:4 n-1; HDTA). However, intracellular bioconversion and metabolic fate of n-1 polyunsaturated fatty acids (PUFA) remain unclear. Therefore, in this study, we aimed to assess the intracellular bioconversion and metabolic fate of HDTA and its metabolite, 8,11,14,17- octadecatetraenoic acid (C18:4 n-1; ODTA), using HepG2 cells. Based on the results of cell viability and cytotoxicity assays for HDTA and ODTA, the concentration of each fatty acid supplemented in the experiments was set at 10 μM. HepG2 cell culture with HDTA revealed C20:4 n-1 as a new HDTA metabolite, along with previously reported ODTA. Our findings suggest that the HDTA taken up by HepG2 cells undergoes elongation to form ODTA and C20:4 n-1. Following supplementation with HDTA, ODTA, and 5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; EPA), fatty acids disappeared from the culture medium within 24 h. Notably, the total relative level of HDTA and its metabolites, including ODTA and C20:4 n-1 in HDTA- and ODTA-supplemented cells were significantly lower than the total relative level of EPA and its metabolites, including 7,10,13,16,19-docosapentaenoic acid (C22:5 n-3), C24:6 n-3, and 4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3) in the EPA-supplemented cells. Except for a portion that was intracellularly elongated, most HDTA was taken up by HepG2 cells and may undergo rapid fatty acid β-oxidation. However, RNA-sequencing and real-time polymerase chain reaction analysis revealed no significant changes in fatty acid β-oxidation–related gene expression levels in HDTA-supplemented cells. Collectively, these results provide novel insights into the intracellular bioconversion mechanisms and metabolic fate of HDTA and ODTA in HepG2 cells, suggesting that the metabolic fate of n-1 PUFA is distinct from that of common PUFA. No potential conflict of interest relevant to this article was reported.

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

Acta Medica Okayama 2025 Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma EN Hiroki KOBAYASHI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Bioscientifica Acta Medica Okayama 2052-0573 2025 1 2025 Adult hypophosphatasia presenting with recurrent acute joint pain e240121 EN Hayao Yoshida Department of Diabetes and Endocrinology, Shiga General Hospital Takaaki Murakami Department of Diabetes and Endocrinology, Shiga General Hospital Atsubumi Ogawa Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine Takashi Sunouchi Division of Nephrology and Endocrinology, The University of Tokyo Hospital Naoko Hidaka Division of Nephrology and Endocrinology, The University of Tokyo Hospital Nobuaki Ito Osteoporosis Center, The University of Tokyo Hospital Hiromi Murakami Department of Genomic Medicine, Kyoto University Graduate School of Medicine Hidenori Kawasaki Department of Genomic Medicine, Kyoto University Graduate School of Medicine Tomoyuki Akiyama Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsumi Nakajima Department of Diabetes and Endocrinology, Shiga General Hospital Daisuke Yabe Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine Taizo Yamamoto Department of Diabetes and Endocrinology, Shiga General Hospital Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5′-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation 399 404 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Sasau Matsumoto Department of Surgery, Oomoto Hospital Takehiro Takama Department of Surgery, Oomoto Hospital Yuka Isozaki Department of Surgery, Oomoto Hospital Shigeki Murakami Department of Surgery, Oomoto Hospital Case Report 10.18926/AMO/69442 Gastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus 381 385 EN Atsunobu Sakurai Department of Radiology, NHO Iwakuni Clinical Center Takayuki Yabuki Department of Radiology, NHO Iwakuni Clinical Center Hideki Aoki Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center Akiko Iseki Department of Pathology, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/69439 We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0091-6749 156 2 2025 Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy 473 479.e1 EN Hiroshi Nihira Department of Pediatrics, Kyoto University Graduate School of Medicine Daisuke Nakajima Department of Applied Genomics, Kazusa DNA Research Institute Kazushi Izawa Department of Pediatrics, Kyoto University Graduate School of Medicine Yusuke Kawashima Department of Applied Genomics, Kazusa DNA Research Institute Hirofumi Shibata Department of Pediatrics, Kyoto University Graduate School of Medicine Ryo Konno Department of Applied Genomics, Kazusa DNA Research Institute Motoko Higashiguchi Department of Pediatrics, Kyoto University Graduate School of Medicine Takayuki Miyamoto Department of Pediatrics, Kyoto University Graduate School of Medicine Masahiko Nishitani-Isa Department of Pediatrics, Kyoto University Graduate School of Medicine Eitaro Hiejima Department of Pediatrics, Kyoto University Graduate School of Medicine Yoshitaka Honda Department of Pediatrics, Kyoto University Graduate School of Medicine Tadashi Matsubayashi Department of Pediatrics, Seirei Hamamatsu General Hospital Takashi Ishihara Department of Pediatrics, Nara Medical University Masato Yashiro Department of Pediatrics, Okayama University Naomi Iwata Department of Infection and Immunology, Aichi Children’s Health and Medical Center Yoko Ohwada Department of Pediatrics, Dokkyo Medical University School of Medicine Seiichi Tomotaki Department of Pediatrics, Kyoto University Graduate School of Medicine Masahiko Kawai Department of Neonatology, Kyoto University Graduate School of Medicine Kosaku Murakami Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine Hidenori Ohnishi Department of Pediatrics, Gifu University Graduate School of Medicine Masataka Ishimura Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University Satoshi Okada Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences Motoi Yamashita Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) Tomohiro Morio Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) Akihiro Hoshino Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) Hirokazu Kanegane Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) Kohsuke Imai Department of Pediatrics, National Defense Medical College Yasuko Nakamura Department of Pediatrics, National Defense Medical College Shigeaki Nonoyama Department of Pediatrics, National Defense Medical College Toru Uchiyama Department of Human Genetics, National Center for Child Health and Development Masafumi Onodera Department of Human Genetics, National Center for Child Health and Development Takashi Ishikawa Division of Immunology, National Center for Child Health and Development Toshinao Kawai Division of Immunology, National Center for Child Health and Development Junko Takita Department of Pediatrics, Kyoto University Graduate School of Medicine Ryuta Nishikomori Department of Pediatrics and Child Health, Kurume University School of Medicine Osamu Ohara Department of Applied Genomics, Kazusa DNA Research Institute Takahiro Yasumi Department of Pediatrics, Kyoto University Graduate School of Medicine Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.<br> Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).<br> Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.<br> Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus–like pathways.<br> Conclusion: Upregulation of the interferon pathway exists already at birth—not only in neonates with type I interferonopathy but also in other IEIs, including CGD. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2667-2421 18 2025 Postnatal expression of Cat-315-positive perineuronal nets in the SAMP10 mouse primary somatosensory cortex 244 256 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Perineuronal nets (PNNs) form at the end of the critical period of plasticity in the mouse primary somatosensory cortex. PNNs are said to have functions that control neuroplasticity and provide neuroprotection. However, it is not clear which molecules in PNNs have these functions. We have previously reported that Cat-315-positive molecules were not expressed in the PNNs of the senescence-accelerated model (SAM)P10 strain model mice at 12 months of age. To confirm whether the loss of Cat-315-positive molecules occurred early in life in SAMP10 mice, we examined Cat-315-positive PNNs in the primary somatosensory cortex during postnatal development. This research helps to elucidate the function of PNNs and the mechanism of cognitive decline associated with ageing. To confirm whether Cat-315-positive PNNs changed in an age-dependent manner in SAMP10 mice, we examined the primary somatosensory cortex at 21, 28, and 56 days after birth. We compared these results with those of senescence-accelerated mouse-resistant (SAMR) mice. In SAMP10 mice, Cat-315-positive PNNs were expressed in the primary somatosensory cortex early after birth, but their expression was significantly lower than that in SAMR1 mice. Many other molecules that calibrated the PNN were unchanged between SAMP10 and SAMR1 mice. This study revealed that the expression of the Cat-315 epitope was decreased in the primary somatosensory cortex of SAMP10 mice during postnatal development. SAMP10 mice have had histological abnormalities in their brains since early life. Furthermore, using SAMP10 will be useful in elucidating the mechanism of age-related abnormalities in brain function as well as in elucidating the function and structure of PNNs. No potential conflict of interest relevant to this article was reported.

Walter de Gruyter GmbH Acta Medica Okayama 2081-6936 16 1 2025 Age-related behavioural abnormalities in C57BL/6.KOR–Apoe shl mice EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Tetsuji Miyazaki Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Spontaneously hyperlipidaemic (Apoeshl) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoeshl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoeshl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoeshl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoeshl mice to investigate the behavioural abnormalities associated with ageing in Apoeshl mice. In this study, 7-month-old Apoeshl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoeshl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoeshl mice showed decreased anxiety-like behaviour. Moreover, Apoeshl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoeshl mice changes with age. However, 11-month-old Apoeshl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoeshl mice can be used to investigate the function of ApoE in the central nervous system. No potential conflict of interest relevant to this article was reported.

Walter de Gruyter GmbH Acta Medica Okayama 2081-6936 16 1 2025 Rearing in an envy-like environment increases anxiety-like behaviour in mice EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0953-4180 2024 2024 Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour 9215607 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test. 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 Coronary cross-sectional area stenosis severity determined using coronary CT highly correlated with coronary functional flow reserve: a pilot study 26737 EN Takuto Koumoto Division of Radiation, Okayama Heart Clinic Shozo Kusachi Okayama University Graduate School of Health Sciences Takumi Tomiya Division of Cardiovascular Intervention, Okayama Heart Clinic Takuya Akagi Division of Cardiovascular Intervention, Okayama Heart Clinic Hiroshi Kawamura Division of Cardiovascular Medicine, Okayama Heart Clinic Satoshi Hirohata Okayama University Graduate School of Health Sciences Hirosuke Yamaji Division of Cardiovascular Medicine, Okayama Heart Clinic Takashi Murakami Division of Cardiovascular Medicine, Okayama Heart Clinic Shigeshi Kamikawa Division of Cardiovascular Intervention, Okayama Heart Clinic Masaaki Murakami Division of Cardiovascular Intervention, Okayama Heart Clinic Fractional flow reserve (FFR) is the gold standard for assessing the physiological significance of coronary stenosis. We examined the potential correlation between digitally measured coronary cross-sectional area stenosis using coronary computed tomography (CT) angiography and FFR. We analyzed data of 32 consecutive patients with stenoses who underwent invasive FFR determination. The cross-sectional area was assessed using 128-slice coronary detector-based spectral CT angiography. Power analysis revealed that the sample size enabled the detection of an area under the receiver operating characteristic (ROC) curve (AUC) of 0.90. FFR ≤ 0.8 and > 0.8 were defined as FFR-positive and FFR-negative, respectively. Intra- and interobserver differences were negligible. Percentage cross-sectional area stenosis was calculated as 100 × (A−B)/A, where A is the cross-sectional area at non-stenotic pre-stenotic segment and B is the cross-sectional area of the most severe stenotic lesion. AUC indicated that percentage cross-sectional area stenosis effectively discriminated between FFR-positive and FFR-negative cases, yielding a sensitivity of 0.882 and specificity of 0.933 at a cutoff of 50% area reduction, with an AUC of 0.976. Lesions with less than 45% cross-sectional area stenosis on coronary CT angiography were not FFR-positive. When ROC analysis was conducted for lesion characteristics, AUC did not significantly improve. In conclusion, the percent coronary cross-sectional area stenosis measured using coronary CT angiography distinguished between FFR-positive and FFR-negative lesions with high accuracy. The severity of coronary cross-sectional area stenosis determined using CT angiography is clinically useful for predicting FFR. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1076-0296 31 2025 Activated Clotting Time Requires Adaptation Across Altered Measurement Devices: Determination of Appropriate Range During Atrial Fibrillation Ablation EN Haruna Sakanoue Department of Nursing, Okayama Heart Clinic Hirosuke Yamaji Heart Rhythm Center, Okayama Heart Clinic Sayaka Okamoto Department of Nursing, Okayama Heart Clinic Kumi Okano Department of Nursing, Okayama Heart Clinic Yuka Fujita Department of Nursing, Okayama Heart Clinic Shunichi Higashiya Heart Rhythm Center, Okayama Heart Clinic Takashi Murakami Heart Rhythm Center, Okayama Heart Clinic Satoshi Hirohata Department of Medical Technology, Okayama University Graduate School of Health Sciences Shozo Kusachi Department of Medical Technology, Okayama University Graduate School of Health Sciences Background: Methods for measuring activated clotting time (ACT) are not yet standardized.<br> Objectives: To adjust and compare values between two measurement systems and to optimize ACT during atrial fibrillation (AF) ablation.<br> Methods: Two systems were compared: electromagnetic detection using a rotating tube (EM system; Hemochron Response) and photo-optical detection using a cartridge immersed in blood (PO system; ACT CA-300TM).<br> Results: ACT was measured simultaneously in 124 instances in 53 patients before and during AF ablations using both methods. A linear regression analysis showed ACT (EM system) = 1.19 × ACT (PO system) + 9.03 (p < .001, r = 0.90). Bland–Altman plots indicated an average difference of 50 s between the two systems. In 3364 ACT measurements from 1161 ablations, the EM system recorded a mean ACT of 320 ± 44 s (range 156-487 s). Estimating the target range as mean ± 1 SD range, the EM system's range was 275-365 s, in 5-s increments. The pre-ablation ACT measured on the EM system was 143 ± 28 s (115-170 s). Cardiac tamponade occurred in 4 out of 2085 ablations (0.19%) over 5 years, with ACT values ranging from 330 to 391 s on the EM system. Based on these findings, the estimated optimal ACT range for the PO system was adjusted to 225-300 s to align with the EM system's range of 275-365 s.<br> Conclusions: ACT target ranges should be system-specific, and direct extrapolation between devices is not recommended. Adjustment is clinically necessary when switching systems. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 A Rare Presentation of Pneumonic-Type Adenocarcinoma Hidden behind Empyema 305 309 EN Satoru Senoo Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Eito Niman Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center Ryoko Tsuji Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Kohei Takata Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Shunsuke Matsumori Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Fumika Murano Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Yuka Sugisaki Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Hiroki Omori Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Akihiko Taniguchi Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Rika Omote Department of Diagnostic Pathology, National Hospital Organization Fukuyama Medical Center Eiki Ichihara Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Kenji Takahashi Department of General Thoracic Surgery, National Hospital Organization Fukuyama Medical Center Toshiaki Okada Department of Respiratory Medicine, National Hospital Organization Fukuyama Medical Center Case Report 10.18926/AMO/69158 Pneumonic-type adenocarcinoma (P-ADC) can closely mimic pneumonia. We report a P-ADC initially diagnosed as pneumonia which developed into a pulmonary abscess and empyema. A 50-year-old Japanese male diagnosed with pneumonia, pulmonary abscess, and empyema was administered antibiotics and a chest tube for drainage, which improved his symptoms and blood test results. However, chest computed tomography showed an enlarged infiltrative shadow. The patient underwent bronchoscopy and was diagnosed with an adenocarcinoma. This case highlights the importance of considering P-ADC in differential diagnoses when a pneumonia-like shadow enlarges post-empyema treatment. Diagnostic and clinical tests, e.g., bronchoscopy, should be performed in such cases. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Anterior Uveitis Secondary to an Infected Postoperative Maxillary Cyst 283 286 EN Yuta Imamura 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 Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Hosokawa 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 Hiroya Kindo 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 Aya Murai Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/69154 A 76-year-old man presented with right eyelid swelling and deteriorated vision. Examination revealed anterior uveitis with hypopyon and a visual acuity of 20/2,000 in the right eye, with no abnormalities in the left. Computed tomography revealed enlargement of the right maxillary sinus and internal fluid accumulation, suggesting a postoperative maxillary cyst (POMC). Nasal endoscopic surgery drained the pus by opening the lower wall of the maxillary cyst. Following the procedure, intraocular inflammation resolved, and visual acuity in the right eye improved to 24/20. This is the first reported case of uveitis secondary to POMC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 The Work Productivity of Cancer-survivor and Non-cancer-survivor Workers 243 251 EN Mika Kamano Department of Public Health, Faculty of Medicine, Kagawa University Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Nlandu Roger Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Akitsu Murakami Cancer Center, Kagawa University Hospital Yusuke Yamadori Department of Anesthesiology, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/69149 We investigated the work productivity levels of employed cancer survivors and non-cancer-survivor workers by conducting a cross-sectional study in Japan between February and March 2019, using an online survey. A total of 561 employed individuals aged 20-64 years were analyzed. Work productivity was assessed using the Work Productivity and Activity Impairment-General Health questionnaire which evaluates absenteeism, presenteeism, and overall work productivity loss. The questionnaire responses demonstrated that the cancer survivors within 1 year of diagnosis had significantly higher absenteeism compared to the non-cancer workers (p=0.048). Although presenteeism and overall work productivity loss were also higher in the non-cancer-survivor group, the differences were not significant. Cancer survivors within 1 year of diagnosis exhibited higher absenteeism, but their work productivity appeared to recover to levels comparable to those of the non-cancer workers over time. These findings may contribute to workplace policies supporting cancer survivors’ return to work. 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.

Elsevier BV Acta Medica Okayama 0169-5002 199 2025 Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study 108027 EN Hidehito Horinouchi Department of Thoracic Oncology, National Cancer Center Hospital Haruyasu Murakami Department of Thoracic Oncology, Shizuoka Cancer Center Hideyuki Harada Division of Radiation Therapy, Shizuoka Cancer Center Tomotaka Sobue Division of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University Tomohiro Kato Department of Respiratory Medicine, National Hospital Organization Himeji Medical Cente Shinji Atagi Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center Takaaki Tokito Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University Hospital Satoshi Oizumi Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center Masahiro Seike Department of Pulmonary Medicine and Oncology, Nippon Medical School Hospital Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Tadashi Mio Department of Respiratory Medicine, National Hospital Organization Kyoto Medical Center Takashi Sone Department of Respiratory Medicine, Kanazawa University Hospital Chikako Iwao Department of Medical, AstraZeneca K.K. Takeshi Iwane Department of Medical, AstraZeneca K.K. Ryo Koto Department of Medical, AstraZeneca K.K. Masahiro Tsuboi Department of Thoracic Surgery, National Cancer Center Hospital East Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.<br> Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan–Meier method.<br> Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy—61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group—42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group—37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).<br> Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-8051 144-145 2025 Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques 109001 EN Takanori Sasaki Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Sadaaki Kimura Astellas Pharma Inc. Akihiro Noda Astellas Pharma Inc. Yoshihiro Murakami Astellas Pharma Inc. Sosuke Miyoshi Astellas Pharma Inc. Masaru Akehi Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuhiko Ochiai School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University Masami Watanabe Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Higuchi Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Eiji Matsuura Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.<br> Methods: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.<br> Results: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.<br> Conclusion: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 137 1 2025 令和５年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞） 7 9 EN Tomohiro Urata Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 2 2025 Safe Resection of Esophageal Cancer with a Non-Recurrent Inferior Laryngeal Nerve Associated with an Aberrant Right Subclavian Artery Using Intraoperative Nerve Monitoring 139 144 EN Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Hospital Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Hospital Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Hospital Yohei Mizusawa Department of Gastroenterological Surgery, Okayama University Hospital Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Hospital Yuhei Kondo Department of Gastroenterological Surgery, Okayama University Hospital Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Hospital Yukinori Tanoue Department of Gastroenterological Surgery, Okayama University Hospital Masashi Hashimoto Department of Gastroenterological Surgery, Okayama University Hospital Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Hospital Case Report 10.18926/AMO/68654 In thoracic esophageal cancer, lymph node dissection around the recurrent laryngeal nerve is crucial but poses a risk of nerve palsy, affecting postoperative quality of life. In cases with an aberrant right subclavian artery (ARSA), the right recurrent laryngeal nerve is absent, and the non-recurrent inferior laryngeal nerve (NRILN) enters the larynx directly from the vagus nerve in the cervical region. Identifying the course of the NRILN is vital to avoid injury. A case of esophageal cancer with an ARSA, in which the course of the NRILN was preserved using the Nerve Integrity Monitoring (NIM) system during surgery, is described. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2052-8817 12 1 2025 Association of blood carboxyhemoglobin levels with mortality and neurological outcomes in out-of-hospital cardiac arrest e70053 EN Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto 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 Tomohiro Hiraoka Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuya Murakami Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Aokage Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Carbon monoxide (CO), produced endogenously by heme oxygenase-1, plays a crucial role in the immune system by mitigating cellular damage under stress. However, the significance of carboxyhemoglobin (COHb) levels after out-of-hospital cardiac arrest (OHCA) is not well understood. This study aimed to explore the association between COHb levels at hospital arrival and within the first 24 h post-arrival with 30-day mortality and neurological outcomes in patients who experienced OHCA.<br> Methods: This single-center, retrospective study analyzed data from adult patients who experienced OHCA seen at Okayama University Hospital from 2019 to 2023. The patients were assigned to one of two study groups based on COHb levels (0.0% or >= 0.1%) upon hospital arrival. The primary outcome was 30-day mortality.<br> Results: Among the 560 eligible patients who experienced OHCA, 284 (50.7%) were in the COHb 0.0% group and 276 (49.3%) were in the COHb >= 0.1% group. The 30-day mortality was significantly higher in the COHb 0.0% group compared to the COHb >= 0.1% group (264 [92.9%] vs. 233 [84.4%]). Multivariable logistic regression showed that the COHb 0.0% group was associated with 30-day mortality (adjusted ORs: 2.24, 95% CIs: 1.10-4.56). Non-survivors at 30 days who were admitted to the intensive care unit had lower COHb levels at hospital arrival (0.0% vs. 0.2%) and lower mean COHb levels during the first 24 h post-arrival (0.7% vs. 0.9%) compared to survivors.<br> Conclusions: COHb levels of 0.0% were linked to worse outcomes in patients experiencing OHCA, warranting further research on the prognostic implications of COHb in this context. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Photoinitiators Induce Histamine Production in Human Mast Cells 51 58 EN Taro Miura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Kawasaki Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University Hirofumi Hamano Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68362 Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4´-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 114 2025 Effects of dark respiration on dry matter production of various crop species 1 10 EN Kuniyuki Saitoh Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiro Murakami Graduate School of Natural Science and Technology, Okayama University Yumi Nakamura School of Agriculture, Okayama University Misa Nishibori School of Agriculture, Okayama University Yuki Takagoshi Graduate School of Natural Science and Technology, Okayama University Yoshihiko Hirai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University 　Eleven crops were cultivated: maize, sunflower, soybean, groundnuts, sesame, kenaf, barley, wheat, rice, potato, and sweet potato. The crop growth rate (CGR) and specific dark-respiration rate (Rs) were measured, and growth efficiency GE =CGR/(CGR+R) (R, respiratory loss) was calculated. In each crop, whole-plant Rs reached a maximum in the earlier stages of growth, declined rapidly until the early reproductive growth, and remained almost constant during the ripening period. The Rs of leaves was higher than that of stems during the reproductive growth period, except for maize and potato. The Rs of storage organs was highest in the earlier stages, followed by a rapid decline to similar or lower values than those of leaves and stems during the ripening period. The GE in whole plant was higher than 60% in wheat, maize, barley, sunflower, rice, kenaf, sesame, but lower in soybean, sweet potato and groundnuts, and lowest in potato, which was affected by the higher respiratory loss. The GE in whole plant during the reproductive growth period was significantly lower, which we attributed to increased maintenance costs due to the increase of non-assimilative organs, and decrease in the dry weight of vegetative organs. A positive correlation was observed between the carbohydrate content of storage organs and GE, indicating that a crop with higher carbohydrate content in storage organs tended to have a higher GE. Crops with higher protein and crude fat content in storage organs tended to have lower GE. The GE over the growing season was low for kenaf, a fiber crop which contains high molecular weight compounds such as lignin and cellulose, and lower for sesame, groundnuts, and soybean, which contain high oil and protein and have high respiration costs for the synthesis of storage materials, suggesting that these higher respiration costs are related to lower dry matter production and hence lower yields. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 22 2024 Microdetection of Nucleocapsid Proteins via Terahertz Chemical Microscope Using Aptamers 7382 EN Xue Ding Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mana Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hirofumi Inoue Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several methods have been employed, including the detection of viral ribonucleic acid (RNA), nucleocapsid (N) proteins, spike proteins, and antibodies. RNA detection, primarily through polymerase chain reaction tests, targets the viral genetic material, whereas antigen tests detect N and spike proteins to identify active infections. In addition, antibody tests are performed to measure the immune response, indicating previous exposure or vaccination. Here, we used the developed terahertz chemical microscope (TCM) to detect different concentrations of N protein in solution by immobilizing aptamers on a semiconductor substrate (sensing plate) and demonstrated that the terahertz amplitude varies as the concentration of N proteins increases, exhibiting a highly linear relationship with a coefficient of determination (R2 = 0.9881), indicating that a quantitative measurement of N proteins is achieved. By optimizing the reaction conditions, we confirmed that the amplitude of the terahertz wave was independent of the solution volume. Consequently, trace amounts (0.5 μL) of the N protein were successfully detected, and the detection process only took 10 min. Therefore, this study is expected to develop a rapid and sensitive method for the detection and observation of the SARS-CoV-2 virus at a microdetection level. It is anticipated that this research will significantly contribute to reducing the spread of novel infectious diseases in the future. No potential conflict of interest relevant to this article was reported.

Japan Medical Association Acta Medica Okayama 2433-3298 6 2 2023 Disease and Injury Trends following Heavy Rains in Western Japan in 2018 129 137 EN Chiaki Hashimoto Department of Epidemiology, Graduate School of Medicine, Density and Pharmaceutical Sciences Okayama University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Density and Pharmaceutical Sciences Okayama University Kazuharu Murakami Mabi Memorial Hospital Shigeru Suganami Association of Medical Doctors of Asia Introduction: Torrential rains occurred in Okayama in western Japan in July 2018, forcing local residents to evacuate. Few studies have reported early-phase disease and injury trends among patients following torrential rains. Thus, in this study, we assessed the illness and injury trends among patients who visited temporary medical facilities located in the areas affected by the 2018 torrential rains; these facilities opened 10 d after the disaster.<br> Methods: We evaluated the trends among patients who visited a medical clinic located in the area in western Japan affected by heavy rains in 2018. We reviewed medical charts related to 1,301 outpatient visits and conducted descriptive analyses.<br> Results: More than half of the patients were over 60 years old. The patients experienced mild injuries (7.9% of total visits) as well as common diseases such as hypertensive diseases (30%), diabetes mellitus (7.8%), acute upper respiratory infections (5.4%), skin diseases (5.4%), and eye diseases (4.8%). Hypertensive diseases were the main cause of a visit in any week. Eye problems were the second-highest reason for a visit in the first week, but there was a relative decrease from the first to the third week. Additionally, the proportion of injuries and skin diseases increased from the first to the second week, from 7.9% to 11.1% for injuries, and from 3.9% to 6.7% for skin diseases.<br> Conclusions: The types of diseases changed on a weekly basis. Older adults needed medical support for longer than other age groups. Prior preparedness such as earlier deployment of such temporary clinics can help mitigate the damage to the victims. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-4991 14 20 2024 Colossal Dielectric Constant of Nanocrystalline/Amorphous Homo-Composite BaTiO3 Films Deposited via Pulsed Laser Deposition Technique 1677 EN Shinya Kondo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taichi Murakami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Loick Pichon Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications Joel Leblanc-Lavoie Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications Takashi Teranishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Kishimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khakani, My Ali El Khakani Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications We report the pulsed laser deposition (PLD) of nanocrystalline/amorphous homo-composite BaTiO3 (BTO) films exhibiting an unprecedented combination of a colossal dielectric constant (epsilon(r)) and extremely low dielectric loss (tan delta). By varying the substrate deposition temperature (T-d) over a wide range (300-800 degrees C), we identified T-d = 550 degrees C as the optimal temperature for growing BTO films with an epsilon(r) as high as similar to 3060 and a tan delta as low as 0.04 (at 20 kHz). High-resolution transmission electron microscopy revealed that the PLD-BTO films consist of BTO nanocrystals (similar to 20-30 nm size) embedded within an otherwise amorphous BTO matrix. The impressive dielectric behavior is attributed to the combination of highly crystallized small BTO nanograins, which amplify interfacial polarization, and the surrounding amorphous matrix, which effectively isolates the nanograins from charge carrier transport. Our findings could facilitate the development of next-generation integrated dielectric devices. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Effect of Radon Inhalation on Murine Brain Proteins: Investigation Using Proteomic and Multivariate Analyses 387 399 EN Shota Naoe Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Reiju Takenaka Graduate School of Health Sciences, Okayama University Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Takaaki Miyaji Advanced Science Research Center, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/67663 Radon is a known risk factor for lung cancer; however, it can be used beneficially, such as in radon therapy. We have previously reported the enhancement of antioxidant effects associated with trace amounts of oxidative stress as one of the positive biological effects of radon inhalation. However, the biological effects of radon inhalation are incompletely understood, and more detailed and comprehensive studies are required. Although several studies have used proteomics to investigate the effects of radon inhalation on body proteins, none has focused on brain proteins. In this study, we evaluated the expression status of proteins in murine brains using proteomic and multivariate analyses to identify those whose expressions changed following two days of radon inhalation at a concentration of 1,500 Bq/m3. We found associations of radon inhalation with the expressions of seven proteins related to neurotransmission and heat shock. These proteins may be proposed as biomarkers indicative of radon inhalation. Although further studies are required to obtain the detailed biological significance of these protein alterations, this study contributes to the elucidation of the biological effects of radon inhalation as a low-dose radiation. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Training high-performance deep learning classifier for diagnosis in oral cytology using diverse annotations 17591 EN Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Futa Tanaka Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takeshi Hara Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Takanaga Ochiai Division of Oral Pathogenesis and Disease Control, Department of Oral Pathology, Asahi University School of Dentistry Katsumitsu Shimada Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Yuta Inoue Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Yoshihiro Taki Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Fumi Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Yasuhiro Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Takanori Ishihama Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Ryo Miyazaki Stony Brook Cancer Center, Stony Brook University Satoshi Murakami Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minoru Miyake Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine The uncertainty of true labels in medical images hinders diagnosis owing to the variability across professionals when applying deep learning models. We used deep learning to obtain an optimal convolutional neural network (CNN) by adequately annotating data for oral exfoliative cytology considering labels from multiple oral pathologists. Six whole-slide images were processed using QuPath for segmenting them into tiles. The images were labeled by three oral pathologists, resulting in 14,535 images with the corresponding pathologists' annotations. Data from three pathologists who provided the same diagnosis were labeled as ground truth (GT) and used for testing. We investigated six models trained using the annotations of (1) pathologist A, (2) pathologist B, (3) pathologist C, (4) GT, (5) majority voting, and (6) a probabilistic model. We divided the test by cross-validation per slide dataset and examined the classification performance of the CNN with a ResNet50 baseline. Statistical evaluation was performed repeatedly and independently using every slide 10 times as test data. For the area under the curve, three cases showed the highest values (0.861, 0.955, and 0.991) for the probabilistic model. Regarding accuracy, two cases showed the highest values (0.988 and 0.967). For the models using the pathologists and GT annotations, many slides showed very low accuracy and large variations across tests. Hence, the classifier trained with probabilistic labels provided the optimal CNN for oral exfoliative cytology considering diagnoses from multiple pathologists. These results may lead to trusted medical artificial intelligence solutions that reflect diverse diagnoses of various professionals. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis 259 270 EN Gonul Vural Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Esra Demir Department of Neurology, Ankara City Hospital Sadiye Gumusyayla Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Funda Eren Department of Clinical Biochemistry, Ankara City Hospital Serdar Barakli Department of Neurology, Ankara City Hospital Salim Neselioglu Department of Clinical Biochemistry, Ankara City Hospital Ozcan Erel Department of Clinical Biochemistry, Ankara City Hospital Original Article 10.18926/AMO/67201 The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol–disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients’ sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol–disulfide homeostasis and ischaemia-modified albumin were measured.<br> We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol–disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol–disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol–disulfide homeostasis in multiple sclerosis patients. No potential conflict of interest relevant to this article was reported.

BMJ Publishing Group Acta Medica Okayama 2052-4897 12 3 2024 Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3) e004237 EN Asami Ueno Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Koki Mise Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Yamaguchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ayaka Kanno Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ichiro Nojima Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Chigusa Higuchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kenichi Shikata Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Miyamoto Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Jun Eguchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Akihiro Katayama Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Mayu Watanabe Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Tatsuaki Nakato Department of Internal Medicine, Okayama Saiseikai General Hospital Atsuhito Tone Department of Internal Medicine, Okayama Saiseikai General Hospital Sanae Teshigawara Okayama Saiseikai General Hospital Takashi Matsuoka Department of Diabetic Medicine, Kurashiki Central Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Kazutoshi Murakami Department of Diabetic Medicine, Kurashiki Central Hospital Ikki Shimizu Sakakibara Heart Institute of Okayama Katsuhito Miyashita Japanese Red Cross Okayama Hospital Shinichiro Ando Okayama City General Medical Center Tomokazu Nunoue Nunoue Clinic Jun Wada Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.<br> Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.<br> Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.<br> Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2024 The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study EN Taku MURAKAMI 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 78 2 2024 The Relationships among Internalized Stigma, Sense of Coherence, and Personal Recovery of Persons with Schizophrenia Living in the Community 171 184 EN Aya Kuramoto Graduate School of Health Sciences, Okayama University Shinya Saito Graduate School of Health Sciences, Okayama University Kumi Watanabe School of Nursing, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/66926 We investigated (i) the relationships among internalized stigma (IS), sense of coherence (SOC), and the personal recovery (PR) of persons with schizophrenia living in the community, and (ii) how to improve the support for these individuals. A questionnaire survey on IS, SOC, and PR was sent by mail to 270 persons with schizophrenia living in the community who were using psychiatric daycare services, of whom 149 responded and 140 were included in the analysis. We established a hypothetical model in which IS influences PR, and SOC influences IS and PR, and we used structural equation modeling to examine the relationships among these concepts. The goodness of fit was acceptable. Our findings suggest that rather than directly promoting PR, SOC promotes PR by mitigating the impact of IS. It is important for nurses/supporters to support individuals with schizophrenia living in the community so that they have opportunities to reflect on their own experiences through their activities and to share their experiences with peers. Nurses/supporters themselves should also reflect on their own support needs. Our findings suggest that this will lead to a reduction of IS and the improvement of SOC, which will in turn promote personal recovery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD 123 134 EN Kyosuke Saeki Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Keisuke Seike Department of Hematology and Oncology, Okayama University Hospital Taiga Kuroi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Takehiro Tanaka Department of Pathology, 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 Nobuharu Fujii Division of Transfusion, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66915 Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT. No potential conflict of interest relevant to this article was reported.

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

SAGE Publications Acta Medica Okayama 2324-7096 12 2024 Pericardial Effusion in Association With Periodontitis: Case Report and Review of 8 Patients in Literature EN Toshihiko Matsuo Okayama University Chie Nakago Matsuo Okayama University Nobuhiko Matsuo Okayama University Ayano Mori Nagashima Hospital Masaaki Murakami Okayama Heart Clinic Hiroshi Ito Okayama University Periodontal diseases are well-known background for infective endocarditis. Here, we show that pericardial effusion or pericarditis might have origin also in periodontal diseases. An 86-year-old man with well-controlled hypertension and diabetes mellitus developed asymptomatic increase in pericardial effusion. Two weeks previously, he took oral new quinolone antibiotics for a week because he had painful periodontitis along a dental bridge in the mandibular teeth on the right side and presented cheek swelling. The sputum was positive for Streptococcus species. He was healthy and had a small volume of pericardial effusion for the previous 5 years after drug-eluting coronary stents were inserted at the left anterior descending branch 10 years previously. The differential diagnoses listed for pericardial effusion were infection including tuberculosis, autoimmune diseases, and metastatic malignancy. Thoracic to pelvic computed tomographic scan demonstrated no mass lesions, except for pericardial effusion and a small volume of pleural effusion on the left side. Fluorodeoxyglucose positron emission tomography disclosed many spotty uptakes in the pericardial effusion. The patient denied pericardiocentesis, based on his evaluation of the risk of the procedure. He was thus discharged in several days and followed at outpatient clinic. He underwent dental treatment and pericardial effusion resolved completely in a month. He was healthy in 6 years until the last follow-up at the age of 92 years. We also reviewed 8 patients with pericarditis in association with periodontal diseases in the literature to reveal that periodontal diseases would be the background for developing infective pericarditis and also mediastinitis on some occasions. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1869-2044 73 1 2023 Exploratory study of volatile fatty acids and the rumen-and-gut microbiota of dairy cows in a single farm, with respect to subclinical infection with bovine leukemia virus 31 EN Takehito Suzuki School of Veterinary Medicine, Azabu University Hironobu Murakami School of Veterinary Medicine, Azabu University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Reiichiro Sato Faculty of Agriculture, University of Miyazaki Iyo Takemura-Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masaya Ogata School of Veterinary Medicine, Azabu University Kazuyuki Sogawa School of Veterinary Medicine, Azabu University Hiroho Ishida School of Veterinary Medicine, Azabu University Apichart Atipairin School of Pharmacy, Walailak University Osamu Matsushita Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Makoto Nagai School of Veterinary Medicine, Azabu University Background Subclinical infection with bovine leukemia virus (BLV) in cows can cause economic losses in milk and meat production in many countries, as BLV-related negative effects. The volatile fatty acids (VFAs) and microbiota present in the digestive tracts of cows can contribute to cow health. Here, we exploratorily investigated the VFAs and microbiota in the rumen and gut with respect to subclinical BLV infection using cows housed at a single farm.<br> Results We analyzed a herd of 38 cows kept at one farm, which included 15 uninfected and 23 BLV-infected cows. First, the analysis of the VFAs in the rumen, gut, and blood revealed an absence of statistically significant differences between the uninfected and BLV-infected groups. Thus, BLV infection did not cause major changes in VFA levels in all tested specimens. Next, we analyzed the rumen and gut microbiota. The analysis of the microbial diversity revealed a modest difference between the uninfected and BLV-infected groups in the gut; by contrast, no differences were observed in the rumen. In addition, the investigation of the bacteria that were predominant in the uninfected and BLV-infected groups via a differential abundance analysis showed that no significant bacteria were present in either of the microbiota. Thus, BLV infection possibly affected the gut microbiota to a small extent. Moreover, bacterial associations were compared between the uninfected and BLV-infected groups. The results of this analysis suggested that BLV infection affected the equilibrium of the bacterial associations in both microbiota, which might be related to the BLV-related negative effects. Thus, BLV infection may negatively affect the equilibrium of bacterial associations in both microbiota.<br> Conclusions Subclinical BLV infection is likely to affect the rumen and gut microbiota, which may partly explain the BLV-related negative effects. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Quantitative Assessment of the Heat Transfer Capacity of Ice Bags and their Cooling Effects on the Skin Surface and Core Temperature 53 61 EN Yukiko Ichikawa Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University Tetsuya Ogino Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University Original Article 10.18926/AMO/66671 Ice bags are frequently used in medical care settings for pain relief, comfort, and in some cases, whole-body cooling. This study quantifies heat energy transfer capacity of ice bags and evaluates their cooling effects on body temperature. Forty-eight healthy adults in their 20s were recruited. An ice bag wrapped in two layers of dry towel was applied to the forehead, neck, or palm of each participant for 10 min. The skin surface temperature, heat flow, and core temperature were recorded during the cooling and non-cooling periods, with energy transfer calculated by integrating heat flow over time. Over the non-cooling period, 31.4-53.6 kJ·m-2 of energy was dissipated over 10 min, whereas during the cooling period, the range increased to 180.0-218.7 kJ·m-2 over 10 min. Skin surface temperature decreased by 3.2-5.7°C, whereas core temperature was unchanged. Ice bag use augmented energy transfer by about 150-180 kJ·m-2 over 10 min, but this was insufficient for rapid whole body cooling due to the small skin-surface area in contact with the ice bag. The measured energy transfer indicated that topical ice bag application absorbs insufficient energy to affect core temperature. Quantitative assessment of energy transfer was shown to inform the safe and appropriate use of thermotherapy. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 7 24 2023 Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study 7459 7470 EN Tomohiro Urata Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Naoi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aixiang Jiang British Columbia Cancer, Centre for Lymphoid Cancer Merrill Boyle British Columbia Cancer, Centre for Lymphoid Cancer Kazutaka Sunami Department of Hematology, NHO Okayama Medical Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuichiro Nawa Division of Hematology, Ehime Prefectural Central Hospital Yasushi Hiramatsu Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Kazuhiko Yamamoto Department of Hematology and Oncology, Okayama City Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital Isao Yoshida Department of Hematologic Oncology, NHO Shikoku Cancer Center Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital Ryota Chijimatsu Center for Comprehensive Genomic Medicine, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Ikeuchi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kobayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuma Tani Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ujiie Center for Comprehensive Genomic Medicine, Okayama University Hospital Hirofumi Inoue Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Keisuke Sawada Department of Pathology, Saitama Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Jun-ichi Tamaru Department of Pathology, Saitama Medical Center, Saitama Medical University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences David W. Scott British Columbia Cancer, Centre for Lymphoid Cancer Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-5204 15 2023 Collapse-related traumatic intracranial hemorrhage following out-of-hospital cardiac arrest: A multicenter retrospective cohort study 100418 EN Fumiya Inoue Department of Emergency Medicine, Hiroshima City Hospital Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihisa Ichiba Department of Emergency Medicine, Hiroshima City Hospital Takayuki Otani Department of Emergency Medicine, Hiroshima City Hospital Hiroshi Naito Department of Emergency Medicine, Hiroshima City Hospital Yoshinori Kosaki Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuya Murakami Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuyoshi Iida Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Yumoto 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 Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Sudden loss of consciousness as a result of cardiac arrest can cause severe traumatic head injury. Collapse-related traumatic intracranial hemorrhage (CRTIH) following out-of-hospital cardiac arrest (OHCA) may be linked to poor neurological outcomes; however, there is a paucity of data on this entity. This study aimed to investigate the frequency, characteristics, and outcomes of CRTIH following OHCA.<br> Methods: Adult patients treated post-OHCA at 5 intensive care units who had head computed tomography (CT) scans were included in the study. CRTIH following OHCA was defined as a traumatic intracranial injury from collapse due to sudden loss of consciousness associated with OHCA. Patients with and without CRTIH were compared. The primary outcome assessed was the frequency of CRTIH following OHCA. Additionally, the clinical features, management, and consequences of CRTIH were analyzed descriptively.<br> Results: CRTIH following OHCA was observed in 8 of 345 enrolled patients (2.3%). CRTIH was more frequent after collapse outside the home, from a standing position, or due to cardiac arrest with a cardiac etiology. Intracranial hematoma expansion on follow up CT was seen in 2 patients; both received anticoagulant therapy, and one required surgical evacuation. Three patients (37.5%) with CRTIH had favorable neurological outcomes 28 days after collapse.<br> Conclusions: Despite its rare occurrence, physicians should pay special attention to CRTIH following OHCA during the post-resuscitation care period. Larger prospective studies are warranted to provide a more explicit picture of this clinical condition. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 A Case of Migration of a Hydrogel Spacer for Radiotherapy into the Pulmonary Artery 647 650 EN Katsuhide Kojima Department of Radiology, Okayama University Hospital Yuka Takahashi Department of Radiology, Okayama University Hospital Soichi Sugiyama Department of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yudai Asano Department of Radiology, Okayama University Hospital Nanako Okawa Department of Radiology, Okayama University Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Fumiyo Higaki Department of Radiology, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Case Report 10.18926/AMO/66157 A 67-year-old man was referred to our hospital for the diagnosis and treatment of prostate cancer. Multidisciplinary discussion led to intensity-modulated radiotherapy preceded by hormone therapy. Before radiotherapy, a biodegradable hydrogel spacer (HS) was placed between the prostate and rectum to reduce radiation injury risk. Three weeks postplacement, pelvic magnetic resonance imaging revealed HS migration into the pelvic vein. Subsequent whole-body contrast-enhanced computed tomography (CECT) revealed HS migration into the pulmonary artery. The patient showed no symptoms or clinical signs. Radiotherapy was completed uneventfully. Complete absorption of the migrated HS was confirmed using CECT images 5 months postplacement. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia 627 634 EN Yumi Hibino Department of Gynecologic Oncology, NHO Shikoku Cancer Center Mika Okazawa-Sakai Department of Gynecologic Oncology, NHO Shikoku Cancer Center Takanori Yokoyama Department of Gynecologic Oncology, NHO Shikoku Cancer Center Etsuko Fujimoto Department of Gynecologic Oncology, NHO Shikoku Cancer Center Shinichi Okame Department of Gynecologic Oncology, NHO Shikoku Cancer Center Norihiro Teramoto Department of Pathology, NHO Shikoku Cancer Center Kazuhiro Takehara Department of Gynecologic Oncology, NHO Shikoku Cancer Center Original Article 10.18926/AMO/66155 To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians’ discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6920 23 1 2023 The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study 859 EN Taku Murakami Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Hideharu Hagiya Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mikako Obika Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiro Mandai Department of Emergency Medicine, The JIKEI University Tomoko Miyoshi Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitomi Kataoka Diversity Enhancement Center, Okayama University Hospital Fumio Otsuka Department of General Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Simulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties.<br> Methods This study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents' medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups.<br> Results A total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation.ConclusionSimulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer 517 525 EN Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hiroyuki Terasawa Department of Gastroenterology and Hepatology, Okayama University Hospital Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Hospital Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Hospital Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Hospital Hironari Kato Department of Gastroenterology and Hepatology, Okayama University Hospital Original Article 10.18926/AMO/65974 We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 5 2023 Associations among Preoperative Malnutrition, Muscle Loss, and Postoperative Walking Ability in Intertrochanteric Fractures: A Retrospective Study 511 516 EN Kohei Sato Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironori Tsuji Department of Orthopedic Surgery, Japanese Red Cross Okayama Hospital Masanori Yorimitsu Department of Orthopedic Surgery, Okayama University Hospital Takenori Uehara Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Okazaki Department of Orthopedic Surgery, Tsuyama Chuo Hospital Shinichiro Takao Department of Orthopedic Surgery, Okayama Medical Center Toshiaki Hata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shiro Fukuoka Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Noda Department of Orthopedic Surgery, Kawasaki Medical School, General Medical Center Hideyuki Kanda Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65973 Sarcopenia and malnutrition are increasing in older adults and are reported risk factors for functional impairment after hip fracture surgery. This study aimed to investigate the associations between skeletal muscle mass loss, malnutrition, and postoperative walking ability in patients with hip fracture. We retrospectively reviewed patients who underwent intertrochanteric fracture surgery at our institute. The psoas muscle index, controlling nutritional status score, and functional ambulation category (FAC) were used to evaluate skeletal muscle mass, nutritional status, and walking ability, respectively. Six months after surgery, walking ability was assessed as either “gait disturbance” or “independent gait”. Multivariate binomial logistic regression analysis, with skeletal muscle mass, nutritional status, and other factors, was used to predict the risk of being assigned to the gait disturbance group. This study included 95 patients (mean age, 85.2 years; 70 women). Sixty-six patients had low skeletal muscle mass, 35 suffered from malnutrition, and 28 had both. Malnutrition and low skeletal muscle mass were significantly associated with postoperative gait disturbance (FAC < 3). Preoperative low skeletal muscle mass and malnutrition were risk factors for postoperative poor walking ability. Further preventive interventions focusing on skeletal muscle mass and nutritional status are required. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 18 8 2023 Selective DNA-binding of SP120 (rat ortholog of human hnRNP U) is mediated by arginine-glycine rich domain and modulated by RNA e0289599 EN Mary Miyaji Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kawano Faculty of Science, Department of Biochemistry, Okayama University of Science Ryohei Furuta Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emi Murakami Faculty of Science, Department of Biochemistry, Okayama University of Science Shogo Ikeda Faculty of Science, Department of Biochemistry, Okayama University of Science Kimiko M. Tsutsui Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Tsutsui Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A human protein heterogeneous ribonucleoprotein U (hnRNP U) also known as Scaffold attachment factor A (SAF-A) and its orthologous rat protein SP120 are abundant and multifunctional nuclear protein that directly binds to both DNA and RNA. The C-terminal region of hnRNP U enriched with arginine and glycine is essential for the interaction with RNA and the N-terminal region of SAF-A termed SAP domain has been ascribed to the DNA binding. We have reported that rat hnRNP U specifically and cooperatively binds to AT-rich DNA called nuclear scaffold/matrix-associated region (S/MAR) although its detailed mechanism remained unclear. In the present study analysis of hnRNP U deletion mutants revealed for the first time that a C-terminal domain enriched with Arg-Gly (defined here as 'RG domain') is predominantly important for the S/MAR-selective DNA binding activities. RG domain alone directly bound to S/MAR and coexistence with the SAP domain exerted a synergistic effect. The binding was inhibited by netropsin, a minor groove binder with preference to AT pairs that are enriched in S/MAR, suggesting that RG domain interacts with minor groove of S/MAR DNA. Interestingly, excess amounts of RNA attenuated the RG domain-dependent S/MAR-binding of hnRNP U. Taken together, hnRNP U may be the key element for the RNA-regulated recognition of S/MAR DNA and thus contributing to the dynamic structural changes of chromatin compartments. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2005 Analysis of gene expression and physiological roles of interleukin-18 in the mouse and rat uterus EN Yousuke Murakami No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2005 Nicorandil reduces the incidence of minor cardiac marker elevation after coronary stenting EN Masaaki Murakami No potential conflict of interest relevant to this article was reported.

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

Nature Portfolio Acta Medica Okayama 2045-2322 13 1 2023 Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists 11676 EN Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Futa Tanaka Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Yuta Inoue Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Takeshi Hara Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Kazumasa Yoshii Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shimada Katsumitsu Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Fumi Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Yasuhiro Nakai Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Ryo Miyazaki Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine Satoshi Murakami Department of Oral Pathology, Graduate School of Oral Medicine, Matsumoto Dental University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minoru Miyake Department of Oral and Maxillofacial Surgery, Kagawa University Faculty of Medicine The study aims to identify histological classifiers from histopathological images of oral squamous cell carcinoma using convolutional neural network (CNN) deep learning models and shows how the results can improve diagnosis. Histopathological samples of oral squamous cell carcinoma were prepared by oral pathologists. Images were divided into tiles on a virtual slide, and labels (squamous cell carcinoma, normal, and others) were applied. VGG16 and ResNet50 with the optimizers stochastic gradient descent with momentum and spectral angle mapper (SAM) were used, with and without a learning rate scheduler. The conditions for achieving good CNN performances were identified by examining performance metrics. We used ROCAUC to statistically evaluate diagnostic performance improvement of six oral pathologists using the results from the selected CNN model for assisted diagnosis. VGG16 with SAM showed the best performance, with accuracy = 0.8622 and AUC = 0.9602. The diagnostic performances of the oral pathologists statistically significantly improved when the diagnostic results of the deep learning model were used as supplementary diagnoses (p-value = 0.031). By considering the learning results of deep learning model classifiers, the diagnostic accuracy of pathologists can be improved. This study contributes to the application of highly reliable deep learning models for oral pathological diagnosis. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2213-0071 45 2023 Mycobacterium shinjukuense infection successfully treated with clarithromycin, rifampicin, and ethambutol 101894 EN Kayo Nakamura Department of Medicine, Japanese Red Cross Society Himeji Hospital Etsuko Murakami Department of Medicine, Japanese Red Cross Society Himeji Hospital Daizo Kishino Department of Medicine, Japanese Red Cross Society Himeji Hospital Shuko Mashimo Department of Medicine, Japanese Red Cross Society Himeji Hospital Yusuke Kurioka Department of Medicine, Japanese Red Cross Society Himeji Hospital Yusaku Shibata Department of Medicine, Japanese Red Cross Society Himeji Hospital Arihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Yasushi Hiramatsu Department of Medicine, Japanese Red Cross Society Himeji Hospital Yoshinobu Maeda Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital We present the case of a 59-year-old woman diagnosed with Mycobacterium shinjukuense infection using mass spectrometry of bronchioalveolar lavage fluid. We initiated treatment with clarithromycin, rifampicin, and ethambutol based on the results of drug susceptibility testing, which improved lung opacities. Most previous cases were treated with the standard regimen for Mycobacterium tuberculosis. However, our regimen may provide a therapeutic option for this rare nontuberculous Mycobacterium infection. No potential conflict of interest relevant to this article was reported.

Japanese Society of Breeding Acta Medica Okayama 1344-7610 73 2 2023 Melon diversity on the Silk Road by molecular phylogenetic analysis in Kazakhstan melons 219 229 EN Katsunori Tanaka Faculty of Agriculture and Life Science, Hirosaki University Mitsuhiro Sugiyama Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization (NARO) Gentaro Shigita Graduate School of Environmental and Life Science, Okayama University Ryoma Murakami Faculty of Agriculture and Life Science, Hirosaki University Thanh-Thuy Duong Faculty of Agronomy, University of Agriculture and Forestry, Hue University Yasheng Aierken Center for Hami Melon, Xinjiang Academy of Agricultural Sciences Anna M Artemyeva All-Russian Institute of Plant Genetic Resources on the name of N.I.Vavilov (VIR) Zharas Mamypbelov Kazakhstan Research Institute of Potato and Vegetable Growing LLC Ryuji Ishikawa Faculty of Agriculture and Life Science, Hirosaki University Hidetaka Nishida Graduate School of Environmental and Life Science, Okayama University Kenji Kato Graduate School of Environmental and Life Science, Okayama University To uncover population structure, phylogenetic relationship, and diversity in melons along the famous Silk Road, a seed size measurement and a phylogenetic analysis using five chloroplast genome markers, 17 RAPD markers and 11 SSR markers were conducted for 87 Kazakh melon accessions with reference accessions. Kazakh melon accessions had large seed with exception of two accessions of weedy melon, Group Agrestis, and consisted of three cytoplasm types, of which Ib-1/-2 and Ib-3 were dominant in Kazakhstan and nearby areas such as northwestern China, Central Asia and Russia. Molecular phylogeny showed that two unique genetic groups, STIa-2 with Ib-1/-2 cytoplasm and STIa-1 with Ib-3 cytoplasm, and one admixed group, STIAD combined with STIa and STIb, were prevalent across all Kazakh melon groups. STIAD melons that phylogenetically overlapped with STIa-1 and STIa-2 melons were frequent in the eastern Silk Road region, including Kazakhstan. Evidently, a small population contributed to melon development and variation in the eastern Silk Road. Conscious preservation of fruit traits specific to Kazakh melon groups is thought to play a role in the conservation of Kazakh melon genetic variation during melon production, where hybrid progenies were generated through open pollination. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0449-3060 64 4 2023 Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice 635 643 EN Shota Naoe Graduate School of Health Sciences, Okayama University Yuki Fujimoto Graduate School of Health Sciences, Okayama University Kaito Murakami Graduate School of Health Sciences, Okayama University Ryohei Yukimine Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate gamma-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2165-0497 11 3 2023 Metataxonomic Analysis of the Uterine Microbiota Associated with Low Fertility in Dairy Cows Using Endometrial Tissues Prior to First Artificial Insemination e04764-22 EN Takuya Yagisawa Hokkaido Agriculture Mutual Aid Association Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Iyo Takemura-Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shun Ando Hokkaido Agriculture Mutual Aid Association Osamu Ichii Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University Hironobu Murakami Laboratory of Infectious Diseases, School of Veterinary Medicine, Azabu University Osamu Matsushita Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Seiji Katagiri Laboratory of Theriogenology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Hokkaido University The deterioration in reproductive performance in association with low fertility leads to significant economic losses on dairy farms. The uterine microbiota has begun to attract attention as a possible cause of unexplained low fertility. We analyzed the uterine microbiota associated with fertility by 16S rRNA gene amplicon sequencing in dairy cows. First, the alpha (Chao1 and Shannon) and beta (unweighted and weighted UniFrac) diversities of 69 cows at four dairy farms that had passed the voluntary waiting period before the first artificial insemination (AI) were analyzed with respect to factors including farm, housing style, feeding management, parity, and AI frequency to conception. Significant differences were observed in the farm, housing style, and feeding management, except parity and AI frequency to conception. The other diversity metrics did not show significant differences in the tested factors. Similar results were obtained for the predicted functional profile. Next, the microbial diversity analysis of 31 cows at a single farm using weighted UniFrac distance matrices revealed a correlation with AI frequency to conception but not with parity. In correlation with AI frequency to conception, the predicted function profile appeared to be slightly modified and a single bacterial taxon, Arcobacter, was detected. The bacterial associations related to fertility were estimated. Considering these, the uterine microbiota in dairy cows can be varied depending on the farm management practices and may become one of the measures for low fertility. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Predictive Factors for Recovery from Alcoholic Liver Failure 169 177 EN Kanae Inoue Department of Gastroenterology, Okayama City Hospital Rio Fujita Department of Gastroenterology, Okayama City Hospital Takatoshi Nagahara Department of Gastroenterology, Okayama City Hospital Shiho Murakami Department of Gastroenterology, Okayama City Hospital Yuta Nagai Department of Gastroenterology, Okayama City Hospital Rina Moriwake Department of Gastroenterology, Okayama City Hospital Nozomi Miyake Department of Gastroenterology, Okayama City Hospital Akiko Wakuta Department of Gastroenterology, Okayama City Hospital Kazuya Kariyama Department of Gastroenterology, Okayama City Hospital Mamoru Nishimura Department of Gastroenterology, Okayama City Hospital Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Original Article 10.18926/AMO/65146 Alcoholic liver disease is a risk factor for non-virus-related hepatocellular carcinoma (HCC), which is increasing in prevalence. This study aimed to identify the factors for recovery from alcoholic liver failure. Sixty-two consecutive patients hospitalized for alcoholic liver failure at Okayama City Hospital were enrolled. The characteristics of patients who survived to the 1-month follow-up and whose liver function improved to Child–Pugh A at 3 months (CPA3) and 12 months (CPA12) were compared with the rest of the patients. The survivors at 1 month (50 patients) were significantly younger than the deceased patients and had better liver and renal function with higher levels of γ-glutamyl transferase (GGT). The same factors, except renal function, were correlated with achieving CPA3. High AST, ALT, and GGT levels as well as short spleen length, total abstinence, and good Child–Pugh scores at admission were identified as factors for achieving CPA12. The extent of alcohol intake before admission was not identified as a risk factor in any analysis. In conclusion, baseline liver function is crucial for survival and achieving CPA3, whereas high transaminase and γ-GTP levels, the absence of splenomegaly, and total abstinence are significant factors for achieving CPA12. No potential conflict of interest relevant to this article was reported.

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

Karger Acta Medica Okayama 1662-6575 15 3 2022 Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia 974 979 EN Hiroyuki Murakami Department of Hematology and Oncology, Okayama University Hospital Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Takeru Asano Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Takashi Moriyama Department of Hematology and Oncology, Okayama University Hospital Akifumi Matsumura Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Tomohiro Toji Department of Pathology, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment. 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 The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus 705 713 EN Toshihiro Higashikawa Kanazawa Medical University Himi Municipal Hospital Tomohiko Ito Kanazawa Medical University Himi Municipal Hospital Takurou Mizuno Kanazawa Medical University Himi Municipal Hospital Keiichiro Ishigami Kanazawa Medical University Himi Municipal Hospital Kengo Kuroki Kanazawa Medical University Himi Municipal Hospital Naoto Maekawa Kanazawa Medical University Himi Municipal Hospital Daisuke Usuda Kanazawa Medical University Himi Municipal Hospital Toshihide Izumida Kanazawa Medical University Himi Municipal Hospital Shinya Yamada Kanazawa Medical University Himi Municipal Hospital Ryusho Sangen Kanazawa Medical University Himi Municipal Hospital Kazu Hamada Kanazawa Medical University Himi Municipal Hospital Jun Kiyosawa Kanazawa Medical University Himi Municipal Hospital Atsushi Saito Kanazawa Medical University Himi Municipal Hospital Masaharu Iguchi Kanazawa Medical University Himi Municipal Hospital Yuji Kasamaki Kanazawa Medical University Himi Municipal Hospital Takeshi Nakahashi Kanazawa Medical University Himi Municipal Hospital Akihiro Fukuda Kanazawa Medical University Himi Municipal Hospital Hitoshi Saito Kanazawa Medical University Himi Municipal Hospital Tsugiyasu Kanda Kanazawa Medical University Himi Municipal Hospital Masashi Okuro Department of Geriatric Medicine, Kanazawa Medical University Original Article 10.18926/AMO/64121 The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=−0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=−0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=−0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 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 Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study EN Naoko KUROOKA 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 Gestational Outcomes and Birth Weight in Japanese Women at the Upper and Lower limits of the Normal BMI range 519 526 EN Yoko Ishioka Graduate School of Health Sciences, Okayama University Hiroyuki Yamashita Yamaguchi Rosai Hospital Kinya Hamaguchi Hamaguchi Women's Clinic Yoshitaka Kuwahara Kuwahara Obstetrics and Gynecology Clinic Kaoru Nakamura Okinawa Kyoudou Hospital Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Original Article 10.18926/AMO/64032 To examine the outcome of gestational blood pressure and birth weight in women with normal pre-pregnancy BMI (18.5-25 kg/m2) who are at the lower and upper limits of this range, i.e., slightly underweight or slightly overweight. Overall, 2,038 Japanese women with low -risk who had delivered during January 2014–December 2016 were classified according to their pre-pregnancy BMI: underweight (< 18.5 kg/m2), slightly underweight (18.5≤BMI<21 kg/m2), normal (21≤BMI<23 kg/m2), slightly overweight (23≤BMI<25 kg/m2) and overweight (≤ 25 kg/m2). Their blood pressure during each trimester and birth weight was evaluated. The slightly overweight group showed a significantly higher blood pressure than the underweight and slightly underweight groups. Birth weight was lower in the slightly underweight than in the slightly overweight group (p<0.01). The incidence rate of “heavy for dates” (HFD) infants was significantly higher in the slightly overweight and overweight groups than in the other groups (p<0.05 and p<0.01, respectively). Weight gain of < 7 kg significantly increased the rate of “light for dates” (LFD) infants, while a weight gain of ≥13 kg significantly increased the rate of HFD infants (p<0.05 and p<0.01, respectively). Blood pressure during pregnancy was ssociated with pre-pregnancy BMI. The birth weight of infants of low-risk pregnant women is affected by both pre-pregnancy BMI and gestational weight gain. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 23 19 2022 Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model 11035 EN Tsukasa Shigehiro Research Institute for Biomedical Sciences, Tokyo University of Science Maho Ueno Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Mayumi Kijihira Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Ryotaro Takahashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Chiho Umemura Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Eman A. Taha Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Chisaki Kurosaka Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Megumi Asayama Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University Hiroshi Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Junichiro Futami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Junko Masuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development. No potential conflict of interest relevant to this article was reported.

Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 84 7 2022 Screening of bacterial DNA in bile sampled from healthy dogs and dogs suffering from liver- or gallbladder-associated disease 1019 1022 EN Sakurako NEO School of Veterinary Medicine, Azabu University Iyo TAKEMURA-UCHIYAMA Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Jumpei UCHIYAMA Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hironobu MURAKAMI School of Veterinary Medicine, Azabu University Ayaka SHIMA Anicom Specialty Medical Institute Inc. Hideki KAYANUMA School of Veterinary Medicine, Azabu University Taiki YOKOYAMA School of Veterinary Medicine, Azabu University Satoshi TAKAGI School of Veterinary Medicine, Azabu University Eiichi KANAI School of Veterinary Medicine, Azabu University Masaharu HISASUE School of Veterinary Medicine, Azabu University Although the biliary system is generally aseptic, gallbladder microbiota has been reported in humans and some animals apart from dogs. We screened and analyzed the bacterial deoxyribonucleic acid in canine gallbladders using bile sampled from 7 healthy dogs and 52 dogs with liver- or gallbladder-associated disease. PCR screening detected bacteria in 17.3% of diseased dogs (9/52) and none in healthy dogs. Microbiota analysis of PCR-positive samples showed that the microbial diversity differed between liver- and gallbladder-associated disease groups. Thus, a specific bacterial community appears to occur at a certain frequency in the bile of diseased dogs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0741-238X 2022 Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetic Kidney Disease: A Multicenter, Open-Label, Prospective Study EN Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Nakajima Department of Internal Medicine, Nakashima Hospital Masami Hashimoto Hashimoto Kidney Clinic Akihiko Nakamura Osafune Clinic Tomokazu Nunoue Nunoue Clinic Kazuharu Murakami Murakami Clinic Takeshi Hosoya Hosoya Clinic Kiichi Komoto Innoshima General Hospital Takashi Taguchi Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Takaaki Akasaka Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Kazuhito Shiosakai Data Intelligence Department, Daiichi Sankyo Co., Ltd. Kotaro Sugimoto Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Introduction<br> Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment.<br> <br> Methods<br> In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR < 30, 30 to < 300, and 300 to < 1000 mg/gCr). Esaxerenone was initiated at 1.25 mg/day and followed by incremental dose escalation based on BP and serum potassium level monitoring. The treatment period was 12 weeks. The primary endpoint was change in morning home systolic BP/diastolic BP (SBP/DBP) from baseline to end of treatment (EOT). Secondary endpoints included achievement rate of target BP, change in UACR from baseline, and safety.<br> <br> Results<br> In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (− 11.6/− 5.2 mmHg, both p < 0.001) and in all UACR subcohorts (all p < 0.001). The target BP achievement rate was 38.5%. Significant reductions in bedtime home and office BPs were also shown in the total population and all UACR subcohorts. UACR significantly improved from baseline to EOT in the total (− 50.9%, p < 0.001) and all UACR subcohorts (all p < 0.001). Incidence of serum potassium elevation as drug-related treatment emergent adverse events was 2.7%. The change from baseline in estimated glomerular filtration rate (eGFR) was − 4.8 mL/min/1.73 m2.<br> <br> Conclusion<br> Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction. No potential conflict of interest relevant to this article was reported.

岡山大学大学院教育学研究科 Acta Medica Okayama 1883-2423 180 2022 Perceived Efficacy and Anxiety of Teachers in Japan toward Supporting Students with Chronic Illness in Mainstream School 27 37 EN Munehisa Yoshitoshi Division of Developmental Studies and Support, Graduate School of Education, Okayama University Yasuko Tsushima Faculty of Education, Shujitsu University Rie Murakami Graduate School of Humanities and Social Sciences, Hiroshima University Kiriko Takahashi Center on Disability Studies, University of Hawaiʻi at Mānoa 10.18926/bgeou/63921 The objective of this study was to examine mainstream school teachers’ anxiety and selfefficacy to teaching students with chronic illness. A survey was completed by 59 elementary and 44 junior high school teachers in Japan. Results indicated that the majority of teacher respondents perceived themselves as inadequate to teach students with chronic illness due to lack of practical knowledge and experience. A high proportion of respondents indicated that they had no academic training (62.1%) and no teaching experience (72.8%) for supporting students with chronic illness. On the other hand, there is a positive relationship between selfefficacy, anxiety level and academic training or teaching experience for supporting students with chronic illness. That is, teachers with practical experience teaching students with chronic illness in the classroom and teachers with more academic training in inclusive approaches demonstrated higher efficacy and lower anxiety than teachers without these experiences or with less training in inclusive teaching approaches. All teachers must be equipped with the extensive knowledge of how best to assist students with chronic illness. Additional efforts are needed to adequately support students with chronic illness in the regular education classroom. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1660-4601 19 17 2022 Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice 10632 EN Takahiro Kataoka Faculty of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Kaito Murakami Graduate School of Health Sciences, Okayama University Yuki Fujimoto Graduate School of Health Sciences, Okayama University Ryohei Yukimine Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m(3) radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 The Association between Preoperative Blood Pressure Elevations and Postoperative Adverse Outcomes after Non-cardiac Surgery: A Single-center Retrospective Observational Study 429 437 EN Yusuke Yamadori Department of Anesthesiology, Faculty of Medicine, Kagawa University Tomohiro Hirao Department of Public Health, Faculty of Medicine, Kagawa University Nlandu R. Ngatu Department of Public Health, Faculty of Medicine, Kagawa University Kanae Kanda Department of Public Health, Faculty of Medicine, Kagawa University Syed Mahfuz Al Hasan Department of Public Health, Faculty of Medicine, Kagawa University Akitsu Murakami Department of Anesthesiology, Faculty of Medicine, Kagawa University Yukinori Mashima Department of Public Health, Faculty of Medicine, Kagawa University Gotaro Shirakami Department of Anesthesiology, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/63902 Blood pressure (BP) often rises before surgery. This study investigated whether BP elevation immediately before surgery was associated with adverse outcomes. Medical records of 11,732 patients (average age: 61 years; male: 47.4%) who underwent non-cardiac elective inpatient surgery under general anesthesia at Kagawa University Hospital between January 2011 and June 2019 were reviewed. Differences between the first BP values measured on the day before surgery and the first BP values in the operating room were defined as Δ systolic BP (ΔSBP) and Δ diastolic BP (ΔDBP). The relationships between ΔSBP/ΔDBP and 30-day mortality, 30-day readmission, and over-the-standard length of hospital stay (OSLOS) were assessed. OSLOS was defined as a hospital stay longer than mean+2 standard deviations and was calculated using the Japanese Diagnosis Procedure Combination data. In univariate analysis, the differences in ΔSBP and ΔDBP between the OSLOS and standard LOS groups were both 2 mmHg. In multivariate logistic regression analysis, only ΔDBP was associated with OSLOS. The adjusted odds ratio (95% confidence interval) for the largest quartile was 1.31 (1.02-1.69) (p<0.05). ΔDBP was associated with OSLOS; however, there may be little need to worry about large ΔSBPs and ΔDBPs in clinical practice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 4 2022 Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse 373 383 EN Fuminori Imafuku Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jin Sun Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sunao Kamimai Department of Medical Neurobiology, Okayama University Medical School Takashi Shimizu Department of Medical Neurobiology, Okayama University Medical School Toshiaki Toyota Department of Medical Neurobiology, Okayama University Medical School Yusei Okamoto Department of Medical Neurobiology, Okayama University Medical School Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Pharmacy, Okayama University Hospital Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63889 Parkinson’s disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone- induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification. No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0266-8254 75 6 2022 Characterization of the oral and fecal microbiota associated with atopic dermatitis in dogs selected from a purebred Shiba Inu colony 1607 1616 EN Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takafumi Osumi Laboratory of Veterinary Internal Medicine, Division of Animal Life Science, Graduate School, Tokyo University of Agriculture and Technology Keijiro Mizukami School of Veterinary Medicine, Azabu University Tomoki Fukuyama School of Veterinary Medicine, Azabu University Ayaka Shima Anicom Specialty Medical Institute Inc. Asaka Unno School of Veterinary Medicine, Azabu University Iyo Takemura‐Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yumi Une Faculty of Veterinary Medicine, Okayama University of Science Hironobu Murakami School of Veterinary Medicine, Azabu University Masahiro Sakaguchi School of Veterinary Medicine, Azabu University Atopic dermatitis (AD) is a chronic and relapsing multifactorial inflammatory skin disease that also affects dogs. The oral and gut microbiota are associated with many disorders, including allergy. Few studies have addressed the oral and gut microbiota in dogs, although the skin microbiota has been studied relatively well in these animals. Here, we studied the AD-associated oral and gut microbiota in 16 healthy and nine AD dogs from a purebred Shiba Inu colony. We found that the diversity of the oral microbiota was significantly different among the dogs, whereas no significant difference was observed in the gut microbiota. Moreover, a differential abundance analysis detected the Family_XIII_AD3011_group (Anaerovoracaceae) in the gut microbiota of AD dogs; however, no bacterial taxa were detected in the oral microbiota. Third, the comparison of the microbial co-occurrence patterns between AD and healthy dogs identified differential networks in which the bacteria in the oral microbiota that were most strongly associated with AD were related with human periodontitis, whereas those in the gut microbiota were related with dysbiosis and gut inflammation. These results suggest that AD can alter the oral and gut microbiota in dogs. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-1702 319 2022 Phylogenic analysis of new viral cluster of large phages with unusual DNA genomes containing uracil in place of thymine in gene-sharing network, using phages S6 and PBS1 and relevant uncultured phages derived from sewage metagenomics 198881 EN Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Iyo Takemura-Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kazuyoshi Gotoh Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shin-ichiro Kato Research Institute of Molecular Genetics, Kochi University Yoshihiko Sakaguchi Department of Microbiology, Kitasato University School of Medicine Hironobu Murakami School of Veterinary Medicine, Azabu University Tomoki Fukuyama School of Veterinary Medicine, Azabu University Mao Kaneki School of Veterinary Medicine, Azabu University Osamu Matsushita Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Bacteriophages (phages) are the most diverse and abundant life-form on Earth. Jumbophages are phages with double-stranded DNA genomes longer than 200 kbp. Among these, some jumbophages with uracil in place of thymine as a nucleic acid base, which we have tentatively termed "dU jumbophages" in this study, have been reported. Because the dU jumbophages are considered to be a living fossil from the RNA world, the evolutionary traits of dU jumbophages are of interest. In this study, we examined the phylogeny of dU jumbophages. First, tBLASTx analysis of newly sequenced dU jumbophages such as Bacillus phage PBS1 and previously isolated Staphylococcus phage S6 showed similarity to the other dU jumbophages. Second, we detected the two partial genome sequences of uncultured phages possibly relevant to dU jumbophages, scaffold_002 and scaffold_007, from wastewater metagenomics. Third, according to the gene-sharing network analysis, the dU jumbophages, including phages PBS1 and S6, and uncultured phage scaffold_002 formed a cluster, which suggested a new viral subfamily/family. Finally, analyses of the phylogenetic relationship with other phages showed that the dU jumbophage cluster, which had two clades of phages infecting Gram-negative and Gram-positive bacteria, diverged from the single ancestral phage. These findings together with previous reports may imply that dU jumbophages evolved from the same origin before divergence of Gram-negative and Gram-positive bacteria. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Sequential Development of Putaminal Hemorrhage and Corona Radiata Infarction in the Same Lenticulostriate Arterial Territory 329 332 EN Yuki Inomata Department of Neurosurgery, Shinshu University School of Medicine Yoshiki Hanaoka Department of Neurosurgery, Shinshu University School of Medicine Yu Fujii Department of Neurosurgery, Shinshu University School of Medicine Toshihiro Ogiwara Department of Neurosurgery, Shinshu University School of Medicine Tetsuyoshi Horiuchi Department of Neurosurgery, Shinshu University School of Medicine Case Report 10.18926/AMO/63743 Putaminal hemorrhage is a common type of spontaneous cerebral hemorrhage. However, to our knowledge, there have been no reports of sequential cerebral hemorrhage and infarction in the same perforating arterial territory. Herein, we present the first reported case of the sequential development of putaminal hemorrhage and corona radiata infarction in the same lenticulostriate arterial (LSA) territory. Early intensive blood pressure lowering treatment may have aggravated ischemic damage. If a patient presents with motor weakness that cannot be explained by putaminal hemorrhage, the sequential development of corona radiata infarction in the same LSA territory should be ruled out. No potential conflict of interest relevant to this article was reported.

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

eLIFE SCIENCES PUBL LTD Acta Medica Okayama 2050-084X 11 2022 Structural basis for the absence of low-energy chlorophylls in a photosystem I trimer from Gloeobacter violaceus e73990 EN Koji Kato Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Tasuku Hamaguchi Biostructural Mechanism Laboratory, RIKEN SPring-8 Center Ryo Nagao Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Keisuke Kawakami Biostructural Mechanism Laboratory, RIKEN SPring-8 Center Yoshifumi Ueno Graduate School of Science, Kobe University Takehiro Suzuki Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science Hiroko Uchida Research Center for Inland Seas, Kobe University Akio Murakami Graduate School of Science, Kobe University Yoshiki Nakajima Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Makio Yokono Institute of Low Temperature Science, Hokkaido University Seiji Akimoto Graduate School of Science, Kobe University Naoshi Dohmae Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science Koji Yonekura Biostructural Mechanism Laboratory, RIKEN SPring-8 Center Jian-Ren Shen Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Photosystem I (PSI) is a multi-subunit pigment-protein complex that functions in light-harvesting and photochemical charge-separation reactions, followed by reduction of NADP to NADPH required for CO2 fixation in photosynthetic organisms. PSI from different photosynthetic organisms has a variety of chlorophylls (Chls), some of which are at lower-energy levels than its reaction center P700, a special pair of Chls, and are called low-energy Chls. However, the sites of low-energy Chls are still under debate. Here, we solved a 2.04-& ANGS; resolution structure of a PSI trimer by cryo-electron microscopy from a primordial cyanobacterium Gloeobacter violaceus PCC 7421, which has no low-energy Chls. The structure shows the absence of some subunits commonly found in other cyanobacteria, confirming the primordial nature of this cyanobacterium. Comparison with the known structures of PSI from other cyanobacteria and eukaryotic organisms reveals that one dimeric and one trimeric Chls are lacking in the Gloeobacter PSI. The dimeric and trimeric Chls are named Low1 and Low2, respectively. Low2 is missing in some cyanobacterial and eukaryotic PSIs, whereas Low1 is absent only in Gloeobacter. These findings provide insights into not only the identity of low-energy Chls in PSI, but also the evolutionary changes of low-energy Chls in oxyphototrophs. 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.

The Society for Free Radical Research Japan Acta Medica Okayama 0912-0009 70 2 2022 Mechanisms of action of radon therapy on cytokine levels in normal mice and rheumatoid arthritis mouse model 154 159 EN Takahiro Kataoka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Kaito Murakami Graduate School of Health Sciences, Okayama University Ryohei Yukimine Graduate School of Health Sciences, Okayama University Yuki Fujimoto Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Fumihiro Mitsunobu Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kiyonori Yamaoka Graduate School of Health Sciences, Okayama University The typical indication of radon therapy is rheumatoid arthritis. Although there are several reports that radon therapy has regulation effects on Th17 cells, there has been no study reporting that radon inhalation affects the immune balance among Th1, Th2, and Th17. The purpose of this study is to examine the cytokine changes after radon inhalation. BALB/c mice inhaled radon at 2,000 Bq/m3 for 2 or 4 weeks. SKG/Jcl mice inhaled radon at 2,000 Bq/m3 for 4 weeks after zymosan administration. The results showed that radon inhalation for 4 weeks activated the immune response of Th1, Th2, and Th17. Moreover, the balance among them was not lost by radon inhalation. Radon inhalation for 4 weeks decreased superoxide dismutase activity and increased catalase activity in spleen. These findings suggest that an imbalance of oxidative stress may contribute to activate the immune response. Although zymosan administration activated Th17 immune response and decreased Th1 and Th2 immune response in SKG/Jcl mice, most cytokines related to Th1, Th2, and Th17 approached the normal level by radon inhalation. These findings suggested that radon inhalation has a different action between SKG/Jcl mice and normal BABL/c mice. This may indicate that radon inhalation has an immunomodulation function. 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.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Rapidly Progressive Stenosis of the Left Main Trunk Ostium Starting 21 Months After Stent Implantation 99 104 EN Yoichiro Naito Department of Cardiovascular Medicine, Fukuyama City Hospital Masaki Yoshikawa Department of Cardiovascular Medicine, Fukuyama City Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoki Kubo Department of Cardiovascular Medicine, Fukuyama City Hospital Hiroyasu Sugiyama Department of Cardiovascular Medicine, Fukuyama City Hospital Hideyuki Suzuki Department of Cardiovascular Medicine, Fukuyama City Hospital Shinpei Fujita Department of Cardiovascular Medicine, Fukuyama City Hospital Yasunori Arai Department of Cardiovascular Medicine, Fukuyama City Hospital Sho Takahashi Department of Cardiovascular Medicine, Fukuyama City Hospital Yuichi Kato Department of Cardiovascular Medicine, Fukuyama City Hospital Yu Yoshida Department of Cardiovascular Medicine, Fukuyama City Hospital Hiroaki Akai Department of Cardiovascular Medicine, Fukuyama City Hospital Shuhei Murakami Department of Cardiovascular Medicine, Fukuyama City Hospital Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/63219 Rapidly progressive in-stent restenosis (ISR) after stent deployment from the left main trunk (LMT) to the left anterior descending artery (LAD) without plaque at the LMT ostium has not been reported. A 60-year-old Japanese man with a history of scleroderma, pulmonary fibrosis, and type 2 diabetes developed acute myocardial infarction of the right coronary artery (RCA) and was treated by emergency percutaneous coronary intervention (PCI) for RCA. Nine days later he underwent PCI from the LMT to the LAD. Follow-up coronary angiography (CAG) at 9 and 21 months post-PCI did not reveal ISR in any lesion, but the patient experienced cardiac arrest at 25 months post-PCI. Emergency CAG after resuscitation revealed ISR of the LMT ostium; emergency PCI was conducted. The development of ISR at the ostium of the LMT although the patient was free of plaque 4 months before is extremely unusual. This rare ISR of the LMT ostium progressed rapidly after follow-up CAG revealed no ISR at 21 months post-stent implantation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Cystic Intracranial Recurrence of Olfactory Neuroblastoma without Accumulation on Fluorine-18-fluorodeoxyglucose Positron Emission Tomography 93 98 EN Yukitomo Ishi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Shigeru Yamaguchi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Kanako C. Hatanaka Department of Surgical Pathology, Hokkaido University Hospital Emi Takakuwa Department of Surgical Pathology, Hokkaido University Hospital Hiroaki Motegi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Taishi Honda Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Hiroyuki Kobayashi Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Shunsuke Terasaka Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Akihiro Homma Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Miki Fujimura Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Kiyohiro Houkin Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Case Report 10.18926/AMO/63218 A 66-year-old man underwent multimodal treatment for olfactory neuroblastoma (ONB). When he was 72 years old, a cystic intracranial lesion without accumulation on fluorine-18-fluorodeoxyglucose positron emission tomography was detected. Surgical resection was performed when the patient was 73 years old. The pathological examination revealed recurrence of ONB, and the patient underwent focal irradiation. At age 81, he presented with a second recurrence in the right occipital lobe with radiological and pathological findings similar to the prior recurrence. This case suggests that pathological confirmation should be considered in cases with atypical radiological findings following the treatment of ONB. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Development and Evaluation of a Short-time Imaging Method for the Clinical Study of the Apparent Diffusion Coefficient Subtraction Method 25 32 EN Kohei Sugimoto 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 Kentaro Hamada Radiological Technology, Graduate School of Health Sciences, Okayama University Abdullah Khasawneh Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Majd Barham Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nouha Tekiki Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Konishi Radiological Technology, Graduate School of Health Sciences, Okayama University Hinata Ishizaka Radiological Technology, Graduate School of Health Sciences, Okayama University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Asaumi Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63205 The apparent diffusion coefficient subtraction method (ASM) was developed as a new restricted diffusionweighted imaging technique for magnetic resonance imaging (MRI). The usefulness of the ASM has been established by in vitro basic research using a bio-phantom, and clinical research on the application of the ASM for the human body is needed. Herein, we developed a short-time sequence for ASM imaging of the heads of healthy volunteers (n=2), and we investigated the similarity between the obtained ASM images and diffusion kurtosis (DK) images to determine the utility of the ASM for clinical uses. This study appears to be the first to report ASM images of the human head. We observed that the short-time sequence for the ASM imaging of the head can be scanned in approx. 3 min at 1.5T MRI. The noise reduction effect of median filter processing was confirmed on the ASM images scanned by this sequence. The obtained ASM images showed a weak correlation with the DK images, indicating that the ASM images are restricted diffusion-weighted images. The new shorttime imaging sequence could thus be used in clinical studies applying the ASM. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 1 2022 Extending Treatment Intervals of R-CHOP Therapy Might Be Acceptable for Some Patients with Non-indolent Non-Hodgkin’s B-cell Lymphoma 17 24 EN Keigo Fujishita Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Sando Yasuhisa 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 Takuya Machida Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Original Article 10.18926/AMO/63204 R-CHOP therapy is generally performed every 3 weeks. We investigated the effects of extending the interval of R-CHOP therapy for > 1 week on the prognoses of patients with non-indolent non-Hodgkin’s B-cell lymphoma. Among the 338 patients with non-indolent non-Hodgkin’s B-cell lymphoma who received initial chemotherapy at our institution, we focused on 178 patients who received R-CHOP therapy and analyzed the outcomes of the patients stratified by the treatment intervals. The estimated 3-year overall survival (OS) for the entire population was 82.1%. Patients treated at intervals of ≥ 4 weeks were significantly older, and they had significantly longer follow-up periods and lower relative dose intensity. But the estimated 3-year OS was comparable to those treated at <4 weeks (83.3% vs. 80.5% p=0.947). In a multivariate analysis, age and the dose of anti-cancer agents had significant impacts on OS, but there was no significant relationship regarding the treatment intervals. Propensity score matching confirmed the same result. R-CHOP therapy every around 4 weeks could achieve relatively good survival in some selected patients with non-indolent non-Hodgkin’s B-cell lymphoma. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2021 Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients with Type 2 Diabetes: A Multicenter Prospective Study with 5-year Follow up（U-CARE Study 2) EN Mariko Imamura Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 2041-6520 2021 Chiral exciplex dyes showing circularly polarized luminescence: extension of the excimer chirality rule EN Kazuto Takaishi Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Sho Murakami Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuhiro Iwachido Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tadashi Ema Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University A series of axially chiral binaphthyls and quaternaphthyls possessing two kinds of aromatic fluorophores, such as pyrenyl, perylenyl, and 4-(dimethylamino)phenyl groups, arranged alternately were synthesized by a divergent method. In the excited state, the fluorophores selectively formed a unidirectionally twisted exciplex (excited heterodimer) by a cumulative steric effect and exhibited circularly polarized luminescence (CPL). They are the first examples of a monomolecular exciplex CPL dye. This versatile method for producing exciplex CPL dyes also improved fluorescence intensity, and the CPL properties were not very sensitive to the solvent or to the temperature owing to the conformationally rigid exciplex. This systematic study allowed us to confirm that the excimer chirality rule can be applied to the exciplex dyes: left- and right-handed exciplexes with a twist angle of less than 90 degrees exhibit (-)- and (+)-CPL, respectively. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Clinical Efficacy and Safety of Sitafloxacin 200 mg Once Daily for Refractory Genitourinary Tract Infections 763 766 EN Takehiro Iwata Department of Urology, Okayama University Hospital Takuya Sadahira Department of Urology, Okayama University Hospital Yuki Maruyama Department of Urology, Okayama University Hospital Takanori Sekito Department of Urology, Okayama University Hospital Kasumi Yoshinaga Department of Urology, Okayama University Hospital Shogo Watari Department of Urology, Okayama University Hospital Kentaro Nagao Department of Urology, Okayama University Hospital Tatsushi Kawada Department of Urology, Okayama University Hospital Yusuke Tominaga Department of Urology, Okayama University Hospital Shingo Nishimura Department of Urology, Okayama University Hospital Atsushi Takamoto Department of Urology, Okayama University Hospital Tomoko Sako Department of Urology, Okayama University Hospital Kohei Edamura Department of Urology, Okayama University Hospital Yasuyuki Kobayashi Department of Urology, Okayama University Hospital Motoo Araki Department of Urology, Okayama University Hospital Ayano Ishii Department of Urology, Okayama University Hospital Masami Watanabe Department of Urology, Okayama University Hospital Toyohiko Watanabe Department of Urology, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Hospital Koichiro Wada Department of Urology, Okayama University Hospital Clinical Study Protocol 10.18926/AMO/62820 The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants. 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 The Significance of Age and Causative Bacterial Morphology in the Choice of an Antimicrobial Agent to Treat Acute Uncomplicated Cystitis 719 724 EN Shinya Uehara Department of Urology, Abiko Toho Hospital Kei Fujio Department of Urology, Abiko Toho Hospital Tomoya Yamasaki Department of Urology, Abiko Toho Hospital Hideo Otsuki Department of Urology, Abiko Toho Hospital Original Article 10.18926/AMO/62812 Differentiating patients by age and causative bacterial morphology might aid in making the appropriate choice of antimicrobial agent when treating acute uncomplicated cystitis. In this retrospective analysis, the non-susceptibility rates of the causative bacteria to cefcapene-pivoxil (CFPN-PI) and levofloxacin (LVFX) were determined after dividing patients with acute uncomplicated cystitis by age group (15-54 and 55-74 years old) and by bacterial morphology: gram-positive cocci (GPC) or gram-negative rod (GNR). The overall non-susceptibility rates for CFPN-PI and LVFX were 19.4% and 15.3%, respectively. When the subjects were divided by age, only the non-susceptibility rate for LVFX in the younger group significantly decreased (to 8.7%). When the groups were divided by both age and bacterial morphology, the younger GNR group had non-susceptibility rates of 6.9% to CFPN-PI and 7.8% to LVFX, whereas the younger GPC group showed 10.2% non-susceptibility to LVFX. The older GNR group showed 9.8% non-susceptibility to CFPN-PI, while the older GPC group showed 7.2% non-susceptibility to LVFX. All the non-susceptibility rates were lower than 10.2% in the sub-divided groups. Differentiating patients by age and the morphology of causative bacteria can aid in making the appropriate choice of antimicrobial agent and may improve treatment outcomes in patients with acute uncomplicated cystitis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Correlations Among Consistency, Computed Tomography Values, and Histopathological Subtypes of Spinal Meningioma 713 718 EN Tatsuro Aoyama Department of Neurosurgery, Shinshu University School of Medicine Toshihiro Ogiwara Department of Neurosurgery, Shinshu University School of Medicine Kiyoshi Ito Department of Neurosurgery, Shinshu University School of Medicine Yoshinari Miyaoka Department of Neurosurgery, Shinshu University School of Medicine Yu Fujii Department of Neurosurgery, Shinshu University School of Medicine Yoshiki Hanaoka Department of Neurosurgery, Shinshu University School of Medicine Takatoshi Hasegawa Department of Neurosurgery, Shinshu University School of Medicine Gen Watanabe Department of Neurosurgery, Shinshu University School of Medicine Tatsuya Seguchi Department of Neurosurgery, Seguchi Neurosurgical Hospital Kazuhiro Hongo Department of Neurosurgery, Shinshu University School of Medicine Original Article 10.18926/AMO/62811 The consistency of spinal meningiomas is important to consider when performing tumor removal surgery. This study evaluated the correlations between spinal meningioma consistency and both preoperative computed tomography (CT) values and histopathological subtypes. Fifteen consecutive patients who underwent surgical resection of spinal meningioma at our institution were identified, and preoperative CT values and the signal intensity of T2-weighted magnetic resonance images of the tumor were determined retrospectively. The consistency of the spinal meningioma was defined based on the ultrasonic surgical aspirator output during tumor debulking. Patients were assigned to 2 groups: a soft group (n=4) and a hard group (n=11). The T2 signal intensity was significantly higher in the soft group than in the hard group (p=0.001). While the CT values were considerably higher in the hard group, the difference was not significant (p=0.19). Regarding the histopathological subtypes, psammomatous meningioma exhibited significantly higher CT values than meningothelial meningioma (p=0.019); however, there was a higher frequency of hard tumors in meningothelial meningioma cases than in psammomatous meningioma cases. Although neither robust correlations between tumor consistency and CT values nor a relationship between tumor consistency and histopathological subtype has been established, these results might help with the perioperative manegement of spinal tumors. No potential conflict of interest relevant to this article was reported.

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

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

American Society for Microbiology Acta Medica Okayama 2165-0497 9 1 2021 Use of Recombinant Endolysin to Improve Accuracy of Group B Streptococcus Tests e00077-21 EN Hidehito Matsui Ōmura Satoshi Memorial Institute, Kitasato University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Masaya Ogata School of Veterinary Medicine, Azabu University, Sagamihara Tadahiro Nasukawa School of Veterinary Medicine, Azabu University, Sagamihara Iyo Takemura-Uchiyama School of Veterinary Medicine, Azabu University, Sagamihara Shin-ichiro Kato Kochi University Hironobu Murakami School of Veterinary Medicine, Azabu University, Sagamihara Masato Higashide Kotobiken Medical Laboratories, Inc., Tsukuba Hideaki Hanaki Ōmura Satoshi Memorial Institute, Kitasato University Group B Streptococcus (GBS) causes serious neonatal infection via vertical transmission. The prenatal GBS screening test is performed at the late stage of pregnancy to avoid risks of infection. In this test, enrichment culture is performed, followed by GBS identification. Selective medium is used for the enrichment; however, Enterococcus faecalis, which is a potential contaminant in swab samples, can interfere with the growth of GBS. Such bacterial contamination can lead to false-negative results. Endolysin, a bacteriophage-derived enzyme, degrades peptidoglycan in the bacterial cell wall; it is a promising antimicrobial agent for selectively eliminating specific bacterial genera/species. In this study, we used the recombinant endolysin EG-LYS, which is specific to E. faecalis; the endolysin potentially enriched GBS in the selective culture. First, in the false-negative model (coculture of GBS and E. faecalis, which disabled GBS detection in the subsequent GBS identification test), EG-LYS treatment at 0.1 mg/ml improved GBS detection. Next, we used 548 vaginal swabs to test the efficacy of EG-LYS treatment in improving GBS detection. EG-LYS treatment (0.1 mg/ml) increased the GBS-positive ratio to 17.9%, compared to 15.7% in the control (phosphate-buffered saline [PBS] treatment). In addition, there were an increased number of GBS colonies under EG-LYS treatment in some samples. The results were supported by the microbiota analysis of the enriched cultures. In conclusion, EG-LYS treatment of the enrichment culture potentially improves the accuracy of the prenatal GBS screening test. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 2 2021 令和２年度岡山医学会賞 脳神経研究奨励賞（新見賞） 93 95 EN Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 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.

Springer Science and Business Media LLC Acta Medica Okayama 1029-8428 39 2021 Neuroprotective Effects of Anti-high Mobility Group Box-1 Monoclonal Antibody Against Methamphetamine-Induced Dopaminergic Neurotoxicity 1511 1523 EN Kaori Masai Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keita Kuroda Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nami Isooka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinki Murakami Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sunao Kamimai Department of Medical Neurobiology, Okayama University Medical School Dengli Wang Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keyue Liu Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Nishibori Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences High mobility group box-1 (HMGB1) is a ubiquitous non-histone nuclear protein that plays a key role as a transcriptional activator, with its extracellular release provoking inflammation. Inflammatory responses are essential in methamphetamine (METH)-induced acute dopaminergic neurotoxicity. In the present study, we examined the effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on METH-induced dopaminergic neurotoxicity in mice. BALB/c mice received a single intravenous administration of anti-HMGB1 mAb prior to intraperitoneal injections of METH (4 mg/kg x 2, at 2-h intervals). METH injections induced hyperthermia, an increase in plasma HMGB1 concentration, degeneration of dopaminergic nerve terminals, accumulation of microglia, and extracellular release of neuronal HMGB1 in the striatum. These METH-induced changes were significantly inhibited by intravenous administration of anti-HMGB1 mAb. In contrast, blood-brain barrier disruption occurred by METH injections was not suppressed. Our findings demonstrated the neuroprotective effects of anti-HMGB1 mAb against METH-induced dopaminergic neurotoxicity, suggesting that HMGB1 could play an initially important role in METH toxicity. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2311-5637 7 2 2021 Anti-Inflammatory Effect on Colitis and Modulation of Microbiota by Fermented Plant Extract Supplementation 55 EN Manabu Sugimoto Institute of Plant Science and Resources, Okayama University Toshiro Watanabe Department of Food and Nutrition, Sonoda Women’s University Motoko Takaoka Department of Biosphere Sciences, Kobe College Kyoko Suzuki Department of Biosphere Sciences, Kobe College Tadatoshi Murakami Functional Food Creation Research Institute Co., Ltd. Nobutada Murakami Functional Food Creation Research Institute Co., Ltd. Shoichi Sumikawa Functional Food Creation Research Institute Co., Ltd. Although results of recent studies suggest that fermented foods strongly affect the gut microbiota composition and that they relieve inflammatory bowel disease symptoms, some reports have described that fermented foods increase some inflammation markers based on differences in fermented food materials. This study evaluated the effects of fermented plant extract (FPE) on dextran sulfate sodium (DSS)-induced colitis in mice and the effects on fecal microbiota composition in humans. Mice fed 5% FPE with 3% DSS (FPE group) showed no body weight loss, atrophy of colonic length, or bloody stool, similar to mice fed a basal diet (negative group), whereas mice fed 3% DSS (positive group) exhibited those effects. Concentrations of inflammation markers IL-6 and TNF-alpha were not significantly different between FPE and negative groups; however, those concentrations became higher in the positive group. 16S ribosomal RNA gene sequencing was used to characterize fecal microbiota in healthy women before and after 3-month FPE supplementation. The FPE supplementation induced increases in Firmicutes phyla and in Clostridiales order, which play a central role in inflammation suppression. These results suggest that FPE enhances Clostridiales growth in the gut and that it has an anti-inflammatory effect. 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 Baseline Neutrophil-to-Lymphocyte Ratio and Glasgow Prognostic Score are Associated with Clinical Outcome in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab 335 343 EN Nobuyuki Chikuie Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takao Hamamoto Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Tsutomu Ueda Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takayuki Taruya Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Takashi Kono Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Hiromi Furuie Department of Otorhinolaryngology, Head and Neck Surgery, Kure Medical Center and Chugoku Cancer Center Takashi Ishino Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Sachio Takeno Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Original Article 10.18926/AMO/62228 Recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) has a poor prognosis. Although nivolumab is approved in Japan for treating R/MHNSCC, the response rate is low. Therefore, identifying pretreatment prognostic factors is necessary. This study assessed the utility of the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) as biomarkers of response to nivolumab. We retrospectively collected the data of 56 R/MHNSCC patients treated with nivolumab between May 2017 and December 2019. The Kaplan–Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), and multivariate Cox hazard regression analysis was used to identify independent predictors of survival. Patients with a low pretreatment NLR had prolonged OS, and patients with a low pretreatment GPS had increased OS and PFS. A performance score (PS) of 0-1, development of immune-related adverse events, and GPS of 0-1 were significantly associated with OS in multivariate analysis. In summary, baseline pretreatment NLR and GPS are independently associated with OS in R/MHNSCC patients treated with nivolumab. Administration of nivolumab while maintaining the PS reflects a immune status of the host and leads to a good OS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Interrelationships Between Serum Levels of Procalcitonin and Inflammatory Markers in Patients Who Visited a General Medicine Department 299 306 EN Jo Araki 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 Koichiro Yamamoto 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 Kazuki Tokumasu Hideharu Hagiya 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 Koichi Itoshima Department of Laboratory Medicine, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62221 Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho=0.62), soluble interleukin-2 receptor (sIL-2R; rho=0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho=−0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 3 2021 Clinical Outcome of Palliative Concurrent Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-small Cell Lung Cancer 269 277 EN Kuniaki Katsui Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ogata Department of Radiology, Iwakuni Clinical Center Kenta Watanabe Department of Radiology, Okayama University Hospital Kotaro Yoshio Department of Radiology, Okayama University Hospital Masahiro Kuroda Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka General Thoracic Surgery and Breast and Endocrinological Surgery, 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/62218 Palliative concurrent chemoradiotherapy (CCRT) is often administered to patients with stage III non-small cell lung cancer (NSCLC). We investigated the clinical outcomes of patients receiving palliative CCRT for NSCLC. Data of patients with NSCLC who underwent palliative CCRT (n=16), preoperative CCRT plus surgery (n=97), or definitive CCRT (n=48) were evaluated. In all groups, the concurrent chemotherapy regimens consisted of cisplatin and docetaxel. Rates of local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and prognosis were compared. The 2-year rates of LC, DMFS, PFS, and OS in 16 patients who underwent palliative CCRT were 44.4%, 12.5%, 12.5%, and 18.8%, respectively. Univariate analysis showed that palliative CCRT was associated with poor LC (p<0.001), DMFS (p<0.001), PFS (p<0.001), and OS (p<0.001) outcomes in patients who completed CCRT as a preoperative treatment and poor LC (p=0.01), DMFS (p=0.003), PFS (p=0.04), and OS (p=0.004) outcomes in patients who were considered for definitive CCRT. Although there were some long-term survivors, the clinical outcomes of palliative CCRT were significantly inferior to those of the ideal treatments. Therefore, careful determination of the appropriate treatment indications and further studies are warranted. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2297-055X 8 2021 Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2) 668059 EN Koki Mise Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Imamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Yamaguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chigusa Higuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Katayama Diabetes Center, Okayama University Hospital Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Tatsuaki Nakato Okayama Saiseikai General Hospital Atsuhito Tone Okayama Saiseikai General Hospital Sanae Teshigawara Okayama Saiseikai General Hospital Takashi Matsuoka Kurashiki Central Hospital Shinji Kamei Kurashiki Central Hospital Kazutoshi Murakami Kurashiki Central Hospital Ikki Shimizu The Sakakibara Heart Institute of Okayama Katsuhiro Miyashita Japanese Red Cross Okayama Hospital Shinichiro Ando Okayama City General Medical Center Tomokazu Nunoue Nunoue Clinic Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Yamada GlycoTechnica Ltd. Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2021 APPノックインマウスを用いた咬合支持の欠如によるアミロイドβ沈着の変化 EN Asuka Murakami Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 1 2021 嚢胞形成を伴った管外性の横行結腸平滑筋腫の１例 49 54 EN Kumi Sugiu Department of surgery, Kurashiki Medical Center Yasutaka Kudou Department of surgery, Kurashiki Medical Center Yoshimi Fujimoto Department of surgery, Kurashiki Medical Center Takayoshi Murakami Department of surgery, Kurashiki Medical Center Taiji Tohyama Department of surgery, Kurashiki Medical Center Takuya Nishina Department of surgery, Kurashiki Medical Center Nobutaka Murashima Department of surgery, Kurashiki Medical Center No potential conflict of interest relevant to this article was reported.

Taylor ＆ Francis Ltd. Acta Medica Okayama 2000-2297 13 1 2021 Efficacy of FimA antibody and clindamycin in silkworm larvae stimulated with Porphyromonas gulae 1914499 EN Sho Yoshida Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Inaba Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryota Nomura Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry Masaru Murakami Departments of Pharmacology, Veterinary Public Health II and Molecular Biology, School of Veterinary Medicine, Azabu University Hidemi Yasuda Yasuda Veterinary Clinic Kazuhiko Nakano Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry Michiyo Matsumoto-Nakano Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: Porphyromonas gulae, a major periodontal pathogen in animals, possesses fimbriae that have been classified into three genotypes (A, B, C) based on the diversity of fimA genes encoding fimbrillin protein (FimA). P. gulae strains with type C fimbriae were previously shown to be more virulent than other types. In this study, we further examined the host toxicity mediated by P. gulae fimbriae by constructing recombinant FimA (rFimA) expression vectors for each genotype and raised antibodies to the purified proteins. Methods and Results: All larvae died within 204 h following infection with P. gulae type C at the low-dose infection, whereas type A and B did not. Among fimA types, the survival rates of the larvae injected with rFimA type C were remarkably decreased, while the survival rates of the larvae injected with rFimA type A and type B were greater than 50%. Clindamycin treatment inhibited the growth of type C strains in a dose-dependent manner, resulting in an increased rate of silkworm survival. Finally, type C rFimA-speci?c antiserum prolonged the survival of silkworm larvae stimulated by infection with P. gulae type C strain or injection of rFimA type C protein. Conclusion: These results suggested that type C fimbriae have high potential for enhancement of bacterial pathogenesis, and that both clindamycin and anti-type C rFimA-specific antibodies are potent inhibitors of type C fimbriae-induced toxicity. This is the first report to establish a silkworm infection model using P. gulae for toxicity assessment. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Long-term Survival with a Rare Advanced Primary Gastrointestinal Malignant Melanoma Treated with Laparoscopic Surgery/Immune Checkpoint Inhibitor 231 238 EN Motochika Endo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Asano Department of Surgery, Mitoyo general Hospital Sho Takeda 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 Yoshitaka Kondo 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 Kunitoshi Shigeyasu 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 Takehiro Tanaka Department of Pathology, Okayama University Hospital Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/61906 Targeted therapies for malignant melanoma have improved patients’ prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years. Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine 187 197 EN Yuta Fujiwara Division of Clinical Radiology Service, Okayama Central Hospital Tomoaki Sasaki Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Yuki Muto Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Masaki Hirano Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Ryo Kamizaki Department of Radiological Technology, Faculty of Health Sciences, Okayama University Kaito Murakami Department of Radiological Technology, Faculty of Health Sciences, Okayama University Naoya Miura Department of Radiological Technology, Faculty of Health Sciences, Okayama University Yutaka Fujibuchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Nayu Ohmukai Department of Radiological Technology, Faculty of Health Sciences, Okayama University Nao Ueda Department of Radiological Technology, Faculty of Health Sciences, Okayama University Kouhei Sugimoto Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Kazuhiro Ota Division of Clinical Radiology Service, Okayama Central Hospital Yoshiki Kamihoriuchi Division of Clinical Radiology Service, Okayama Central Hospital Tomoko Sasaki Division of Clinical Radiology Service, Okayama Central Hospital Souichirou Kaneshige Department of Radiology, Okayama Central Hospital Original Article 10.18926/AMO/61897 The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility. 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.

MDPI Acta Medica Okayama 1422-0067 20 3 2019 Region-Specific Neuroprotective Features of Astrocytes against Oxidative Stress Induced by 6-Hydroxydopamine 598 EN Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences Nao Okumura-Torigoe Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences Shinki Murakami Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medical, Dental and Pharmaceutical Sciences In previous studies, we found regional differences in the induction of antioxidative molecules in astrocytes against oxidative stress, postulating that region-specific features of astrocytes lead region-specific vulnerability of neurons. We examined region-specific astrocytic features against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) as an oxidative stress using co-culture of mesencephalic neurons and mesencephalic or striatal astrocytes in the present study. The 6-OHDA-induced reduction of mesencephalic dopamine neurons was inhibited by co-culturing with astrocytes. The co-culture of midbrain neurons with striatal astrocytes was more resistant to 6-OHDA than that with mesencephalic astrocytes. Furthermore, glia conditioned medium from 6-OHDA-treated striatal astrocytes showed a greater protective effect on the 6-OHDA-induced neurotoxicity and oxidative stress than that from mesencephalic astrocytes. The cDNA microarray analysis showed that the number of altered genes in both mesencephalic and striatal astrocytes was fewer than that changed in either astrocyte. The 6-OHDA treatment, apparently up-regulated expressions of Nrf2 and some anti-oxidative or Nrf2-regulating phase II, III detoxifying molecules related to glutathione synthesis and export in the striatal astrocytes but not mesencephalic astrocytes. There is a profound regional difference of gene expression in astrocytes induced by 6-OHDA. These results suggest that protective features of astrocytes against oxidative stress are more prominent in striatal astrocytes, possibly by secreting humoral factors in striatal astrocytes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Minimally Invasive Spinal Stabilization with Denosumab before Total Spondylectomy for a Collapsing Lower Lumbar Spinal Giant Cell Tumor 95 101 EN Keitaro Minato Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Toru Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Tetsuro Yamagishi Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Keigo Watanabe Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Masayuki Ohashi Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Akira Ogose Department of Orthopedic Surgery, Uonuma Kikan Hospital Naoto Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Case Report 10.18926/AMO/61442 A 21-year-old man consulted our hospital for treatment of a spinal giant cell tumor (GCT) of Enneking stage III. Lower lumbar-spine tumors and severe spinal canal stenosis are associated with high risk for surgical mor-bidity. Stability was temporarily secured with a percutaneous pedicle screw fixation in combination with deno-sumab, which shrank the tumor. Total en bloc spondylectomy was then performed 6 months after initiation of denosumab, and the patient was followed for 3 years. There was no local recurrence, and bony fusion was obtained. Minimally invasive surgery and denosumab allowed safer and easier treatment of a collapsing lower lumbar extra-compartmental GCT. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Local Control of Squamous Cell Carcinoma of the Cervix Treated with CT-based Three-dimensional Image-Guided Brachytherapy with or without Central Shielding 79 85 EN Kotaro Yoshio Department of Radiology, Kagawa Prefectural Central Hospital Hisako Nagasaka Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Kento Hisazumi Department of Radiology, Kagawa Prefectural Central Hospital Hiro Okawa 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 Shiro Akaki Department of Radiology, Kagawa Prefectural Central Hospital Susumu Kanazawa Department of Radiology, Okayama University Hospital Tomohiro Mitoma Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Yuri Yano Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Emiko Kobayashi Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Ikuyo Horiguchi Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Masayo Takata Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Atsushi Hongo Department of Obstetrics and Gynecology 2, Kawasaki Medical School, General medical Center Masaru Yonezawa Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Yoshie Nakanishi Department of Obstetrics and Gynecology, Kagawa Prefectural Central Hospital Original Article 10.18926/AMO/61438 The purposes of this retrospective study were to analyze local control of squamous cell carcinoma of the cervix treated with computed tomography (CT)-based image-guided brachytherapy (IGBT), as well as the factors affecting local control. A total of 39 patients were analyzed. The prescribed dose to the pelvis was 45-50 Gy with or without central shielding (CS). IGBT was delivered in 1-5 fractions. The total dose for high-risk clinical target volume (HR-CTV) was calculated as the biologically equivalent dose in 2-Gy fractions. The median follow-up period was 29.3 months. The 2-year overall survival and local control rates were 97% and 91%, respectively. In univariate analysis, the dose covering 90% of the HR-CTV (D90) and tumor size were found to be significant factors for local control. The cutoff values of tumor size and D90 for local control were 4.3 cm (area under the curve [AUC] 0.75) and 67.7 Gy (AUC 0.84) in the CS group and 5.3 cm (AUC 0.75) and 73.7 Gy (AUC 0.78) in the group without CS, respectively. However, though the local control of CT-based IGBT was favorable, the results suggested that the dose required for tumor control may differ depending on the presence of CS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study 45 53 EN Hiroaki Otsuka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kunihisa Kohno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Makoto Nakahama Department of Cardiology, Fukuyama City Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Mitsuru Munemasa Department of Cardiology, Okayama Medical Center Masaaki Murakami Department of Cardiology, Okayama Heart Clinic Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Original Article 10.18926/AMO/61433 Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Treatment Outcomes of Pulmonary Metastases from Head and Neck Squamous Cell Carcinoma 31 37 EN Satoru Miyamaru Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Daizo Murakami Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Kohei Nishimoto Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Haruki Saito Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Yusuke Miyamoto Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Kaoruko Hirota Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Momoko Ise Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Original Article 10.18926/AMO/61431 Although the lung is the most common site of distant metastases from head and neck squamous cell carcinoma (HNSCC), the number of reports about the effects of pulmonary metastasectomy for the treatment of lung metastasis from HNSCC is limited. Metachronous pulmonary metastases were detected in 45 HNSCC patients at Kumamoto University Hospital from 1998 to 2018. Twenty-two patients underwent an operative resection (Ope group) and 23 underwent chemotherapy (Chemo group). The 3-year overall survival (OS) rate and median OS were evaluated. The effects of adjuvant chemotherapy after pulmonary metastasectomy and of new drugs (cetuximab and nivolumab), in the chemo group were also assessed. The 3-year OS rates and median OS were: Ope, 66.1% and 31.5 months; Chemo, 39.7% and 18 months, respectively. In the Ope group, addi-tional recurrences were significantly fewer in the patients who underwent adjuvant chemotherapy post-surgery versus the patients who underwent surgery alone (p = 0.013). In the Chemo group, the 3-year OS rate of the patients who received new drugs was significantly better than that of the patients who did not (p = 0.021). Adjuvant chemotherapy after pulmonary metastasectomy may be a preferable treatment option for preventing recurrences. Cetuximab and nivolumab have a potential to improve OS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer 15 23 EN Kuniaki Katsui Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ogata Department of Radiology, Iwakuni Clinical Center Akihiro Tada Department of Radiology, Okayama Diagnostic Imaging Center Soichi Sugiyama Department of Radiology, Okayama University Hospital Kotaro Yoshio Department of Radiology, Okayama University Hospital Masahiro Kuroda Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Katsuyuki Kiura Allergy and Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/61429 The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0385-5600 64 9 2020 Animal infection models using non‐mammals 585 592 EN Chikara Kaito Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kanade Murakami Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Lina Imai Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University The use of non‐human animal models for infection experiments is important for investigating the infectious processes of human pathogenic bacteria at the molecular level. Mammals, such as mice and rabbits, are also utilized as animal infection models, but large numbers of animals are needed for these experiments, which is costly, and fraught with ethical issues. Various non‐mammalian animal infection models have been used to investigate the molecular mechanisms of various human pathogenic bacteria, including Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa. This review discusses the desirable characteristics of non‐mammalian infection models and describes recent non‐mammalian infection models that utilize Caenorhabditis elegans, silkworm, fruit fly, zebrafish, two‐spotted cricket, hornworm, and waxworm. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 10 1 2020 Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection 20698 EN Ryo Kikuoka Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Natsuki Kubota Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Maeda Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daiki Kagawa Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaaki Moriyama Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Asuka Sato Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinki Murakami Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson's disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1939-4551 13 10 2020 Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study 100463 EN Kiyotake Ogura Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital Noriyuki Yanagida Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital Sakura Sato Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine Takanori Imai Department of Pediatrics, Showa University School of Medicine Komei Ito Department of Allergy, Aichi Children's Health and Medical Center Naoyuki Kando Department of Allergy, Aichi Children's Health and Medical Center Masanori Ikeda Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rumiko Shibata Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital Yoko Murakami Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital Takao Fujisawa Institute for Clinical Research, National Hospital Organization, Mie National Hospital Mizuho Nagao Institute for Clinical Research, National Hospital Organization, Mie National Hospital Norio Kawamoto Department of Pediatrics, Graduate School of Medicine, Gifu University Naomi Kondo Department of Pediatrics, Graduate School of Medicine, Gifu University Atsuo Urisu Department of Pediatrics, Fujita Health University, The Second Teaching Hospital Ikuya Tsuge Department of Pediatrics, Fujita Health University, The Second Teaching Hospital Yasuto Kondo Department of Pediatrics, Fujita Health University, The Second Teaching Hospital Kazuko Sugai Department of Pediatrics, National Hospital Organization, Yokohama Medical Center Osamu Uchida Department of Pediatrics, National Hospital Organization, Yokohama Medical Center Mitsuyoshi Urashima Division of Molecular Epidemiology, The Jikei University School of Medicine Masami Taniguchi Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine Motohiro Ebisawa Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine Background</br> Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described.</br> Methods</br> A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes.</br> Results</br> The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months.</br> Conclusions</br> Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2451-8301 9 2020 Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy 102 114 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Atsumi Shimada Division of Food and Nutrition, Nakamura Gakuen University Junior College Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear.</br> Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules.</br> Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 令和元年度岡山医学会賞 胸部・循環研究奨励賞（砂田賞） 57 59 EN Kiichiro Ninomiya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms 407 413 EN Masaaki Togo Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Yuko Akazawa Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Taro Akashi Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Rika Yamashita Oral Care Center, Nagasaki University Hospital Izumi Yoshitomi JCHO Isahaya General Hospital Kazuo Ohba JCHO Isahaya General Hospital Satsuki Hashimoto JCHO Isahaya General Hospital Hiroko Iwashita JCHO Isahaya General Hospital Tadafumi Kurogi Oral Care Center, Nagasaki University Hospital Yukiko Osada Dental Hygienist's Office, Department of Medical Technology, Nagasaki University Hospital Noriko Wada Dental Hygienist's Office, Department of Medical Technology, Nagasaki University Hospital Yoshifumi Imamura Department of Respiratory Medicine, Nagasaki University Hospital Keiichi Hashiguchi Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Naoyuki Yamaguchi Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Hisayoshi Kondo Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medicine Kazuhiko Nakao Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences Original Article 10.18926/AMO/60800 Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Anaplastic Lymphoma Kinase Fusion: A Review of Therapeutic Drugs and Treatment Strategies 371 379 EN Go Makimoto Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Kadoaki Ohashi Department of Respiratory Medicine, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Review 10.18926/AMO/60796 The prognosis of advanced non-small cell lung cancer (NSCLC) patients has improved in recent decades, especially for patients with an oncogenic driver mutation. Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are effective for patients with the echinoderm microtubule-associated protein-like 4-ALK fusion gene. Several ALK-TKIs have been established: the first-generation ALK-TKI, crizotinib; second-generation ALK-TKIs, alectinib and ceritinib; and third-generation ALK-TKI, lorlatinib. Some ALK-TKIs are effective for tumors that are resistant to other ALK-TKIs; however, as is known in epidermal growth factor receptormutant lung cancer, tumor resistance is inevitable. ALK-positive NSCLCs acquire resistance via various mechanisms, making it a heterogeneous disease. Therefore, it is necessary to develop next-generation treatment strategies, such as the use of next-generation ALK-TKIs for secondary mutations, or combination therapies with ALK-TKIs and other TKIs. In this review, we summarize the development and use of ALK-TKIs, prior pivotal clinical trials, and resistance mechanisms. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 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.

Hindawi Acta Medica Okayama 2090-6528 2020 2020 Eosinophilic Gastritis in a Patient Previously Treated with Dupilumab 6381670 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Toshi Murakami Satsuki Naika Clinic Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shohei Oka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences A 77-year-old Japanese man with bronchial asthma was treated with dupilumab. Dupilumab treatment was discontinued at the patient's request after two injections separated by a 2-week interval. The blood eosinophil count was elevated, and an esophagogastroduodenoscopy performed 3 months after dupilumab treatment revealed gastric ulcers; subsequently, eosinophilic gastritis was diagnosed from biopsy examinations. The gastric lesions were resolved by steroid administration. This case report underscores that eosinophil-associated gastrointestinal diseases should be considered in the differential diagnosis of gastric lesions occurring in patients who were treated with dupilumab. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1065-6995 44 9 2020 G‐CSF‐dependent neutrophil differentiation requires downregulation of MAPK activities through the Gab2 signaling pathway 1919 1933 EN Xianglin Zhao Graduate School of Natural Science and Technology, Okayama University Shun‐ichiro Kawano Graduate School of Natural Science and Technology, Okayama University Junko Masuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hiroshi Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Granulocyte colony‐stimulating factor (G‐CSF) stimulation of myeloid cells induced tyrosine‐phosphorylation of cellular proteins. One of the tyrosine‐phosphorylated proteins was found to be a scaffold protein, Grb2‐associated binding protein 2 (Gab2). Another member of Gab family protein, Gab3, was exogenously overexpressed in neutrophil progenitor cells to make the Gab3 protein to compete with the endogenous Gab2 for the G‐CSF‐dependent signaling. In Gab3‐overexpressed cells, the level of tyrosine phosphorylation of endogenous Gab2 by G‐CSF stimulation was markedly downregulated, while the phosphorylation of Gab3 was significantly enhanced. The Gab3‐overexpressed cells continuously proliferated in the medium containing G‐CSF and lost the ability to differentiate to the mature neutrophil, characterized by the lobulated nucleus. The G‐CSF stimulation‐dependent tyrosine phosphorylation of Gab3, the association of SHP2 to Gab3 and the following mitogen‐activated protein kinase (MAPK) activation were prolonged in the Gab3‐overexpressed cells, compared to the parental cells, where the binding of SHP2 to Gab2 protein and thereby the activation of MAPK were not sustained after G‐CSF stimulation. Inhibition of MAPK by pharmaceutical inhibitor restored the Gab3‐overexpressed cells to the ability to differentiate to mature neutrophil. Therefore, G‐CSF‐dependent Gab2 phosphorylation and following its downregulation led the short‐term MAPK activation. The downregulation of MAPK after transient Gab2 phosphorylation was necessary for the consequent neutrophil differentiation induced by G‐CSF stimulation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Successful Treatment of Staphylococcus schleiferi Infection after Aortic Arch Repair: In Situ Aortic Arch Replacement and Domino Reconstruction of the Debranching Graft using Autologous Iliac Artery 251 255 EN Takashi Murakami Department of aCardiovascular Surgery,Osaka City University Graduate School of Medicine Takanori Tokuda Department of Cardiovascular Surgery, Hirakata Kosai Hospital Shinsuke Nishimura Department of aCardiovascular Surgery,Osaka City University Graduate School of Medicine Hiromichi Fujii Department of aCardiovascular Surgery,Osaka City University Graduate School of Medicine Yosuke Takahashi Department of aCardiovascular Surgery,Osaka City University Graduate School of Medicine Kokoro Yamane Department of aCardiovascular Surgery,Osaka City University Graduate School of Medicine Kazushige Inoue Department of Cardiovascular Surgery, Hirakata Kosai Hospital Koichi Yamada Department of Infection Control Science, Osaka City University Graduate School of Medicine Hiroshi Kakeya Department of Infection Control Science, Osaka City University Graduate School of Medicine Toshihiko Shibata Department of aCardiovascular Surgery,Osaka City University Graduate School of Medicine Case Report 10.18926/AMO/59959 A 62-year-old Japanese male presented with graft infection by Staphylococcus schleiferi 50 days after debranching of the left subclavian artery and frozen elephant trunk repair for the entry closure of a Stanford type B aortic dissection. The graft was removed, and the patient was successfully treated using in situ reconstruction of the arch with omental flap coverage, removal of the debranching graft, autologous iliac artery grafting, and longterm antibiotics. Domino reconstruction of the infected debranching graft using autologous external iliac artery and a Dacron graft can thus be a good option in similar cases. 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 Dkk3/REIC, an N-glycosylated Protein, Is a Physiological Endoplasmic Reticulum Stress Inducer in the Mouse Adrenal Gland 199 208 EN Hirofumi Fujita Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Bando Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichi Oyadomari Division of Molecular Biology, Institute for Genome Research, University of Tokushima Kazuhiko Ochiai Department of Basic Science, School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Kumon Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University Hideyo Ohuchi Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/59950 Dickkopf 3 (Dkk3) is a secreted protein belonging to the Dkk family and encoded by the orthologous gene of REIC. Dkk3/REIC is expressed by mouse and human adrenal glands, but the understanding of its roles in this organ is still limited. To determine the functions of Dkk3 in the mouse adrenal gland, we first identified that the mouse Dkk3 protein is N-glycosylated in the adrenal gland as well as in the brain. We performed proteome analysis on adrenal glands from Dkk3-null mice, in which exons 5 and 6 of the Dkk3 gene are deleted. Twodimensional polyacrylamide gel electrophoresis of adrenal proteins from wild-type and Dkk3-null mice revealed 5 protein spots whose intensities were altered between the 2 genotypes. Mass spectrometry analysis of these spots identified binding immunoglobulin protein (BiP), an endoplasmic reticulum (ER) chaperone. To determine whether mouse Dkk3 is involved in the unfolded protein response (UPR), we carried out a reporter assay using ER-stress responsive elements. Forced expression of Dkk3 resulted in the induction of distinct levels of reporter expression, showing the UPR initiated by the ER membrane proteins of activating transcription factor 6 (ATF6) and inositol-requring enzyme 1 (IRE1). Thus, it is possible that Dkk3 is a physiological ER stressor in the mouse adrenal gland. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2189-7948 20 5 2019 Myxedema coma accompanied by sick sinus syndrome and hypoventilation: A case report 206 208 EN Ko Harada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuntaro Murakami 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 Yu Togawa Department of Internal Medicine, Kaneda Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Myxedema coma is an emergency presentation of hypothyroidism, and cardiopulmonary manifestations of the disease are related to a high mortality rate. We herein report a case of myxedema coma accompanied by sick sinus syndrome requiring temporary cardiac pacing and hypercapnic respiratory failure in an 87-year-old woman. This case is unique because both of the cardiac and pulmonary manifestations were reversible and successfully treated with thyroid hormone replacement. Our case indicates that early detection of the condition and administration of levothyroxine are essential to improve the life-threatening condition and avoid invasive treatment such as permanent pacemaker implantation or intubation. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 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.

岡山大学教師教育開発センター Acta Medica Okayama 2186-1323 10 2020 小学生の読書活動と学校生活スキルとの関連 17 26 EN Natsumi MURAKAMI Mikayo ANDO 10.18926/CTED/58115 児童生徒の問題行動の増加の背景には，日常生活に求められるスキルの低下が一つの原因と考えられている。本研究では，学校生活スキルに着目し，読書活動や読み聞かせを受ける体験との関連について検討することを通して，学校において読書活動の時間を設ける必要性について検討した。また，学校図書への知見を得るため，児童の興味・関心のあるジャンルについても検討した。小学校5，6 年生728 名を対象に，質問紙調査を行った。その結果，いずれの学校生活スキルにおいても，読書活動体験，読み聞かせを受けた体験が多い子どもの方がいずれの体験も少ない子どもに比べて学校生活スキルが高い傾向が示された。そして，現在の子どもの興味・関心のある本のジャンルは，絵本，児童文学，マンガ，小説が多かった。これらのことから，小学校においては，読書活動を継続するとともに，子ども達の関心のあるジャンルをふまえた学校図書館づくりが大切だと考えられた。 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 The Prevalence and Characteristics of Older Japanese Adults with Polypharmacy, Based on Regionally Representative Health Insurance Claims Data 41 48 EN Hoichi Amano Graduate School of Public Health, Teikyo University Kenichi Fujimoto Graduate School of Public Health, Teikyo University Makoto Fujimori Graduate School of Public Health, Teikyo University Natsumi Saka Department of Orthopaedic Surgery, Teikyo University School of Medicine Kyoko Nomura Graduate School of Public Health, Teikyo University Shinichi Tanihara Graduate School of Public Health, Teikyo University Original Article 10.18926/AMO/57951 We aimed to clarify the prevalence of polypharmacy among elderly individuals in Japan. We used the data obtained from a large-scale population-based representative database of health insurance claims in a single prefecture in Japan. We examined all of the outpatient and pharmaceutical health insurance claims for National Health Insurance and those for Late-stage Elderly Health Insurance in Nagasaki Prefecture, Japan between April and June 2016. When two or more claim forms were issued for a patient in a single month, we combined the data and identified the number of prescribed drugs for each person. The definition of polypharmacy is a the prescription of six or more drugs per month. We investigated the prevalence of polypharmacy among the beneficiaries of the two insurance systems. Of the 605,406 beneficiaries of the 2 insurance systems, 121,033 (20.0%) patients with polypharmacy were identified. The prevalence of polypharmacy increased with age, especially among the beneficiaries aged > 85 years, with about half of the beneficiaries having polypharmacy status. About half of the people aged > 85 years in the database had polypharmacy status. When a drug is prescribed to an elderly individual, it is necessary to consider the possibility of polypharmacy-related problems. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 1792-1074 18 3 2019 Cancer stem cell induction from mouse embryonic stem cells 2756 2762 EN Akimasa Seno Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Chikae Murakami Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Bishoy El‑Aarag Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshiaki Iwasaki Health Service Center, Okayama University Toshiaki Ohara Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaharu Seno Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Although cancers are often removed by surgery and treated by chemotherapy and/or radiation therapies, they often reoccur following treatment due to the presence of resistant residual cells such as cancer stem cells (CSCs). CSCs are characterized by their self-renewal, pluripotency, and tumorigenicity properties, and are promising therapeutic targets for the complete therapy of cancers; however, the number of CSCs in cancer tissue is typically too small to investigate fully. We have previously reported that CSCs could be established from induced pluripotent stem cells (iPSCs) using a conditioned medium during cancer cell culture. In the present study, mouse embryonic stem cells (mESCs) were observed to be converted to CSCs (mES-CSCs). This demonstrated that CSC induction does not exclusively occur following gene editing in somatic cells, and that conditioned medium from cancer cells may contain factors that can induce CSCs. Therefore, not only iPSCs but also mESCs, were demonstrated to be able to produce CSCs as one of the potentials of pluripotency of stem cells, suggesting that the conversion to CSCs is not specific to iPSCs. The resultant mES-CSCs would be also useful to generate tissue specific cancers and these naturally occurring cancers can contribute to drug screenings, but also undergo further investigation in order to reveal cancer mechanisms. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 0036-8075 366 6463 2019 An oxyl/oxo mechanism for dioxygen bond formation in PSII revealed by X-ray free electron lasers 334 338 EN Michihiro Suga Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Keitaro Yamashita RIKEN SPring-8 Center Yoshiki Nakajima Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Go Ueno RIKEN SPring-8 Center Hongjie Li Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Takahiro Yamane Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Kunio Hirata RIKEN SPring-8 Center Yasufumi Umena Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Shinichiro Yonekura Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Long-Jiang Yu Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Hironori Murakami Japan Synchrotron Radiation Research Institute Takashi Nomura RIKEN SPring-8 Center Tetsunari Kimura Department of Chemistry, Graduate School of Science, Kobe University Minoru Kubo RIKEN SPring-8 Center Seiki Baba Japan Synchrotron Radiation Research Institute Takashi Kumasaka Japan Synchrotron Radiation Research Institute Kensuke Tono RIKEN SPring-8 Center Makina Yabashi RIKEN SPring-8 Center Hiroshi Isobe Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Kizashi Yamaguchi The Institute for Scientific and Industrial Research, Osaka University Masaki Yamamoto RIKEN SPring-8 Center Hideo Ago RIKEN SPring-8 Center Jian-Ren Shen Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Photosynthetic water oxidation is catalyzed by the Mn4CaO5 cluster of photosystem II (PSII) with linear progression through five S-state intermediates (S0 to S4). To reveal the mechanism of water oxidation, we analyzed structures of PSII in the S1, S2, and S3 states by x-ray free-electron laser serial crystallography. No insertion of water was found in S2, but flipping of D1 Glu189 upon transition to S3 leads to the opening of a water channel and provides a space for incorporation of an additional oxygen ligand, resulting in an open cubane Mn4CaO6 cluster with an oxyl/oxo bridge. Structural changes of PSII between the different S states reveal cooperative action of substrate water access, proton release, and dioxygen formation in photosynthetic water oxidation. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 9 2019 Helping-Like Behaviour in Mice Towards Conspecifics Constrained Inside Tubes 5817 EN Hiroshi Ueno Department of Medical Technology, Graduate School of Health Sciences, Okayama University Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Prosocial behaviour, including helping behaviour, benefits others. Recently, helping-like behaviour has been observed in rats, but whether it is oriented towards rescue, social contact with others, or other goals remains unclear. Therefore, we investigated whether helping-like behaviour could be observed in mice similar to that in rats. Because mice are social animals widely used in neuroscience, the discovery of helping-like behaviour in mice would be valuable in clarifying the psychological and biological mechanisms underlying pro-sociability. We constrained mice inside tubes. Subject mice were allowed to move freely in cages with tubes containing constrained conspecifics. The subject mice released both cagemates and stranger mice but did not engage in opening empty tubes. Furthermore, the same behaviour was observed under aversive conditions and with anesthetised conspecifics. Interestingly, hungry mice opened the tubes containing food before engaging in tube-opening behaviour to free constrained conspecifics. Mice showed equal preferences for constrained and freely moving conspecifics. We demonstrated for the first time that mice show tube-opening behaviour. Furthermore, we partly clarified the purpose and motivation of this behaviour. An effective mouse model for helping-like behaviour would facilitate research on the mechanisms underlying prosocial behaviour. No potential conflict of interest relevant to this article was reported.

IEEE Acta Medica Okayama 2640-009X 2019 2019 DNN-based Voice Conversion with Auxiliary Phonemic Information to Improve Intelligibility of Glossectomy Patients' Speech 138 142 EN Hiroki Murakami Okayama University In this paper, we propose using phonemic information in addition to acoustic features to improve the intelligibility of speech uttered by patients with articulation disorders caused by a wide glossectomy. Our previous studies showed that voice conversion algorithm improves the quality of glossectomy patients' speech. However, losses in acoustic features of glossectomy patients' speech are so large that the quality of the reconstructed speech is low. To solve this problem, we explored potentials of several additional information to improve speech intelligibility. One of the candidates is phonemic information, more specifically Phoneme Labels as Auxiliary input (PLA). To combine both acoustic features and PLA, we employed a DNN-based algorithm. PLA is represented by a kind of one-of-k vector, i.e., PLA has a weight value (<; 1.0) that gradually changes in time axis, whereas one-of-k has a binary value (0 or 1). The results showed that the proposed algorithm reduced the mel-frequency cepstral distortion for all phonemes, and almost always improved intelligibility. Notably, the intelligibility was largely improved in phonemes /s/ and /z/, mainly because the tongue is used to sustain constriction to produces these phonemes. This indicates that PLA works well to compensate the lack of a tongue. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6920 19 1 2019 Effects on postgraduate-year-I residents of simulation-based learning compared to traditional lecture-style education led by postgraduate-year-II residents: a pilot study 87 EN Akira Yamamoto 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 Yasuhiro Mandai Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taku Murakami Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Miyoshi Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideo Ino Center for Education in Medicine and Health Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Kataoka Department of Primary Care and Medical Education, 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:<br/> Simulation-based learning plays an important role in contemporary medical education, although there are problems providing tutors. Peer-assisted learning has begun being formally adopted in medical education. Although it is considered useful for simulation-based learning, its effectiveness remains unclear. This study was designed to compare the effect of simulation-based learning with that of traditional lectures conducted by postgraduate-year (PGY)-II residents on PGY-I residents.<br/> METHODS:<br/> This study was conducted at Okayama University Hospital over three years, for one week each year, before residents entered clinical practice. The study enrolled 76 PGY-I residents, who were randomized into two groups: simulation and lecture groups. PGY-II residents volunteered to conduct simulations and lectures. Knowledge evaluation was performed using pre- and post-tests, and self-evaluation of competence and behaviour-change and program evaluations were conducted using questionnaires.<br/> RESULTS:<br/> In both groups, knowledge test scores were found to improve significantly, and the score difference between pre- and post-tests in both the groups was not significant. Self-evaluation of competence and behaviour-change was found to be higher in the simulation group than the lecture group. The trainees in the simulation group valued the program and the PGY-II residents as teaching staff more than those in the lecture group.<br/> CONCLUSIONS:<br/> The combination of simulation-based learning and peer-assisted learning led by PGY-II residents is potentially more effective in improving the postgraduate education of PGY-I residents than the combination of lecture and peer-assisted learning. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2296634X 7 2019 The Golgin Protein Giantin Regulates Interconnections Between Golgi Stacks 160 EN Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mitsuko Hayashi-Nishino Institute of Scientific and Industrial Research, Osaka University Takuto Shakuno Graduate School of Natural Science and Technology, Okayama University Junko Masuda 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 Runa Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimasa Nakamura raduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura raduate School of Environmental and Life Science, Okayama University Naomi Abe-Kanoh raduate School of Environmental and Life Science, Okayama University Yasuko Honjo esearch Institute for Radiation Biology and Medicine, Hiroshima University Joerg Malsam Center for Biochemistry (BZH), Heidelberg University Sidney Yu School of Biomedical Sciences, The Chinese University of Hong Kong Kunihiko ishino Institute of Scientific and Industrial Research, Osaka University Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi. Giantin knockdown also altered the sizes and numbers of mini Golgi stacks generated by microtubule de-polymerization, suggesting that it maintains the independence of individual Golgi stacks. Therefore, it is presumed that Golgi stacks lose their independence following Giantin knockdown, allowing easier and possibly increased transport among stacks and abnormal glycosylation. To gain structural insights into the independence of Golgi stacks, we herein performed electron tomography and 3D modeling of Golgi stacks in Giantin knockdown cells. Compared with control cells, Giantin-knockdown cells had fewer and smaller fenestrae within each cisterna. This was supported by data showing that the diffusion rate of Golgi membrane proteins is faster in Giantin-knockdown Golgi, indicating that Giantin knockdown structurally and functionally increases connectivity among Golgi cisternae and stacks. This increased connectivity suggests that contrary to the cis-golgin tether model, Giantin instead inhibits the tether and fusion of nearby Golgi cisternae and stacks, resulting in transport difficulties between stacks that may enable the correct glycosylation of proteins and lipids passing through the Golgi. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 A Granulation Polyp in the Colon Masquerading as Metastatic Cancer 457 461 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Takahara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuhiro Yamazaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshitaka Kondo Department of Gastroenterological Surgery, 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 Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/57377 A 60-year-old Caucasian male was diagnosed with lung adenocarcinoma and multiple metastases to the bone, spleen, and brain. He underwent radiotherapy for the brain and lumbar spine metastases, plus chemotherapy (cisplatin and pemetrexed). The chemotherapy was discontinued due to vomiting and hyponatremia, and nivolumab was then administered. Eight months later, 18F-fluorodeoxyglucose positron emission tomography showed tracer uptake in the colon. Colonoscopy revealed a reddish multinodular polyp in the sigmoid colon. The polyp showed irregular microvessels. No colonic mucosal surface structures were observed. Colonic metastasis of the lung carcinoma was highly suspected; the polyp was therefore surgically removed. The histological analysis revealed granulation tissue and suppurative inflammation without neoplastic changes. We diagnosed the lesion as a granulation polyp. Despite the difficulty in diagnosing these lesions due to their rarity and similarity to metastatic colon tumors, we suggest that recognizing the endoscopic features of the polyp surface may allow a preoperative diagnosis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 5 2019 “Active Guide” Brochure Reduces Sedentary Behavior of Elderly People: A Randomized Controlled Trial 427 432 EN Yutaka Owari Shikoku Medical College Hiromi Suzuki Department of Hygiene, Faculty of Medicine, Kagawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Original Article 10.18926/AMO/57373 The aim of this study was to examine in a randomized controlled trial how much the sedentary behavior (sitting time) of community-dwelling elderly Japanese subjects decreased as a result of using the “Active Guide” brochure published by the Ministry of Health, Labour and Welfare (2013) and additional documents related to the benefits of reducing sedentary behavior. A total of 86 elderly people who participated in health-club activities for one year were randomly allocated to two groups. Subjects in the intervention group received explanations of the importance of physical activity using the “Active Guide” brochure (n=42) and additional documents, while subjects in the control group did not (n=44). Physical activity was measured using a triaxial accelerometer for two weeks at baseline and again after one year. After one year of intervention, the difference in the sedentary behavior rate from baseline was −2.2% for the intervention group (n=40) and +2.5% for controls (n=40) (Welch’s t-test, p=0.007). Use of the “Active Guide” brochure and additional documents may reduce the sedentary behavior of community dwelling elderly people in Japan. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 07533322 117 2019 Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice 109038 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801–induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1522-8002 21 7 2019 Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness 627 640 EN Youyi Chen Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences I Wayan Sumardika Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Inoue Faculty of Science and Technology, Division of Molecular Science, Gunma University Hidekazu Iioka Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Yosuke Mitsui Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Saito Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences I Made Winarsa Ruma Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Sato Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Yamauchi Department of Biochemistry, Kawasaki Medical School Hitoshi Murata Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Yamamoto Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Miyoko Kubo Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Endy Widya Putranto Department of Pediatrics, Dr. Sardjito Hospital/Faculty of Medicine, Universitas Gadjah Mada Takashi Murakami Department of Microbiology, Faculty of Medicine, Saitama Medical University Ming Liu Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University Toshihiko Hibino Department of Dermatology, Tokyo Medical University Masahiro Nishibori Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eisaku Kondo Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences Shinichi Toyooka Departments of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0753-3322 115 2019 Comprehensive behavioral study of the effects of vanillin inhalation in mice 108879 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Atsumi Shimada Division of Food and Nutrition, Nakamura Gakuen University Junior College Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Yuko Fujiwara Department of Health and Sports Science, Kawasaki University of Medical Welfare Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Vanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 24518301 6 2019 Layer-specific expression of extracellular matrix molecules in the mouse somatosensory and piriform cortices 1 17 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School In the developing central nervous system (CNS), extracellular matrix (ECM) molecules have regulating roles such as in brain development, neural-circuit maturation, and synaptic-function control. However, excluding the perineuronal net (PNN) area, the distribution, constituent elements, and expression level of granular ECM molecules (diffuse ECM) present in the mature CNS remain unclear. Diffuse ECM molecules in the CNS share the components of PNNs and are likely functional. As cortical functions are greatly region-dependent, we hypothesized that ECM molecules would differ in distribution, expression level, and components in a region- and layer-dependent manner. We examined the layer-specific expression of several chondroitin sulfate proteoglycans (aggrecan, neurocan, and brevican), tenascin-R, Wisteria floribunda agglutinin (WFA)-positive molecules, hyaluronic acid, and link protein in the somatosensory and piriform cortices of mature mice. Furthermore, we investigated expression changes in WFA-positive molecules due to aging. In the somatosensory cortex, PNN density was particularly high at layer 4 (L4), but not all diffuse ECM molecules were highly expressed at L4 compared to the other layers. There was almost no change in tenascin-R and hyaluronic acid in any somatosensory-cortex layer. Neurocan showed high expression in L1 of the somatosensory cortex. In the piriform cortex, many ECM molecules showed higher expression in L1 than in the other layers. However, hyaluronic acid showed high expression in deep layers. Here, we clarified that ECM molecules differ in constituent elements and expression in a region- and layer-dependent manner. Region-specific expression of ECM molecules is possibly related to functions such as region-specific plasticity and vulnerability. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2405-8440 5 6 2019 Anti-stress effects of the hydroalcoholic extract of Rosa gallica officinalis in mice e01945 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Atsumi Shimada Division of Food and Nutrition, Nakamura Gakuen University Junior College Shunsuke Suemitsu Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Naoya Kitamura Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Yuko Fujiwara Department of Health and Sports Science, Kawasaki University of Medical Welfare Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Rosa gallica, a plant of the Rosa genus, has been used widely since the 13th century and is cultivated in many areas as a medicinal plant for the preparation of herbal medicines. However, details of the neuropsychological effects of R. gallica remain unclear; therefore we aimed to investigate the neuropsychological effects of a water-soluble extract of R. gallica in male C57BL/6N mice under normal conditions and under chronic stress. We administered a water-soluble extract of R. gallica to mice and performed a series of behavioral experiments to compare the treated animals with the untreated controls. No significant differences in activity level, anxiety-like behavior, depression-like behavior, body weight, and body temperature were observed between R. gallica-treated mice and control mice. However, in mice subjected to chronic stress, the observed decrease in activity was smaller in the R. gallica-treated mice than in the control mice. The oral administration of R. gallica did not affect the normal behavior of mice. However, when the mice were subjected to stress, R. gallica exerted an anti-stress effect. Therefore, R. gallica has potential as a medicinal plant for the purpose of stress prevention. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 131 1 2019 Ventralight ST®を用いて腹腔鏡下手術で修復した Morgagni 孔ヘルニアの1例 35 39 EN Takayoshi Murakami Department of Surgery, Kurashiki Medical Center Yoshimi Fujimoto Department of Surgery, Kurashiki Medical Center Nobutaka Murashima Department of Surgery, Kurashiki Medical Center Takuya Nishina Department of Surgery, Kurashiki Medical Center Kumi Sugiu Department of Surgery, Kurashiki Medical Center Takamasa Matsumoto Department of Surgery, Kurashiki Medical Center A 78-year-old Japanese woman was referred to our hospital because of fecal occult blood. Barium enema and CT colonography revealed the herniation of the transverse colon and the greater omentum into the right hemithorax through a retrosternal defect. We diagnosed a Morgagni hernia, and we performed a laparoscopic hernia repair with a three-port approach. The invaginated transverse colon and omentum were easily reduced into the abdominal cavity. The size of the hernial orifice was estimated to be approx. 2.5×4 cm. We placed Ventralight ST® mesh over the hernial orifice without hernial sac resection, and we used the double-crown technique to fix the mesh with a hernia stapler. The postoperative course was uneventful, and the patient was discharged on the 5th postoperative day with no complications. There has been no recurrence at 2 years after the surgery. Laparoscopic repair is a safe, less-invasive and useful method for repairing a Morgagni hernia. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Significance of Microcalcifications on Mammography in the Surgical Treatment of Breast Cancer Patients with a Preoperative Diagnosis of Ductal Carcinoma in Situ by Core Needle Biopsy 349 356 EN Hiroshi Isozaki Department of Surgery, Oomoto Hospital Yasuhisa Yamamoto 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/56937 To clarify the surgical outcomes of breast cancer patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) (abbreviated as CNBDCIS), we retrospectively analyzed the cases of 131 patients with CNBDCIS who underwent surgery at Oomoto Hospital (32 total mastectomies, 99 conservative mastectomies). Our analysis of underestimation and predictors of invasive breast cancer of CNBDCIS revealed that the underestimation rate of CNBDCIS was 40.5% (53/131). A logistic regression analysis revealed that palpable tumors (yes to no, odds ratio [OR] 3.25), mammography (MMG) category group (category 4 or 5 to categories 1 , 2, or 3, OR 4.69) and MMG microcalcifications (no to yes, OR 0.24) were significant predictive factors for CNBDCIS invasion. In our analysis of the predictors of positive margins during CNBDCIS surgery, 36 (27.5%) of the 131 patients had positive margins after postoperative pathological examination. A logistic regression analysis revealed that the operative procedure (conservative surgery to total mastectomy, OR 21.4) and MMG microcalcifications (yes to no, OR 3.35) were significant factors related to positive margins during CNBDCIS surgery. Thus, MMG microcalcifications are a negative predictor of upgrading of CNBDCIS and a positive predictor of positive surgical margins for CNBDCIS. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Dynamic Reorganization of Microtubule and Glioma Invasion 285 297 EN Yoshihiro Otani Department of Neurosurgery, The University of Texas Health Science Center at Houston Tomotsugu Ichikawa Department of Neurosurgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56930 Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Safety of Surgical Treatment for Elderly Patients with Gallbladder Carcinoma 241 246 EN Masashi Utsumi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Seitaro Nishimura Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Yuta Une Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Hajime Kashima Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yuji Kimura Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Takashi Arata Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Koh Katsuda Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Kohji Tanakaya Department of Surgery, National Hospital Organization, Iwakuni Clinical Center Original Article 10.18926/AMO/56867 Gallbladder carcinoma (GBC) is a common malignancy with a poor prognosis. With the average life expectancy increasing globally, the incidence of GBC is predicted to increase as well. We investigated the safety and feasibility of surgical treatment for elderly patients with GBC. We retrospectively compared clinical pathological data and treatment outcomes in 45 consecutive GBC patients (23 patients ≥ 75 years [elderly group] and 22 patients < 75 years [younger group]) who underwent curative resection at the Iwakuni Center from January 2008 to December 2017. The proportion of preoperative comorbidities and anticoagulant use was significantly higher in the elderly group. The American Society of Anesthesiologists score was higher in the elderly versus the younger group, and the elderly group had significantly shorter operation times. Reduced activities of daily living was more common in the elderly versus younger group. The percentage of radical resection and overall 3-year survival (66.6% younger vs. 64.4% elderly) were similar between the groups. Controlling Nutritional Status (CONUT) score ≥ 3 and R0 resection were identified as prognostic factors for overall survival rate among all patients. After careful patient selection, 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.

Acta Medica Okayama 2018 The anti-obesity Action of ACAM by modulating the dynamics of cell adhesion and actin polymerization in adipocytes EN Kazutoshi Murakami 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 73 1 2019 Efficacy of Oral Care Provided by Interprofessional Collaboration for a Patient with Esophageal Cancer Associated with Post-polio Syndrome during Neoadjuvant Chemotherapy 71 76 EN Keiko Takahashi-Arimasa Dental Hygienist Team, Division of Medical Technology, Okayama University Hospital Reiko Kohno-Yamanaka Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Yoshihiko Soga Division of Hospital Dentistry, Central Clinical Department, Okayama University Hospital Rumi Miura Dental Hygienist Team, Division of Medical Technology, Okayama University Hospital Manabu Morita Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/56461 Preoperative oral care is helpful to prevent postoperative complications in patients who are undergoing esophagectomy. Here, we report the case of an 81-year-old Japanese man with an upper limb disability caused by post-polio syndrome who was receiving neoadjuvant chemotherapy for esophageal cancer. He had poor oral health status and developed oral complications as a side effect of chemotherapy. He could not brush his teeth by himself. However, infection control by oral care provided by an interprofessional collaboration successfully improved his oral hygiene, and his follow-up involved no severe complications. Interprofessional collaboration is useful especially for patients with upper limb disability. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Impact of Body Mass Index of Japanese Gallbladder Cancer Patients on their Postoperative Outcomes 51 59 EN Masakuni Fujii Department of Internal Medicine, Okayama Saiseikai General Hospital Kenji Fujimoto Department of Public Health, University of Occupational and Environmental Health Syuntaro Yabe Department of Internal Medicine, Okayama Saiseikai General Hospital Junichiro Nasu Department of Internal Medicine, Okayama Saiseikai General Hospital Jiro Miyaike Department of Internal Medicine, Imabari Saiseikai General Hospital Masao Yoshioka Department of Internal Medicine, Okayama Saiseikai General Hospital Junji Shiode Department of Internal Medicine, Okayama Saiseikai General Hospital Kazuhide Yamamoto Department of Internal Medicine, Okayama Saiseikai General Hospital Shinya Matsuda Department of Public Health, University of Occupational and Environmental Health Original Article 10.18926/AMO/56458 　We investigated the relationship between body mass index (BMI) and postoperative outcomes in 450 gallbladder cancer patients in Japan. We collected patient information, including sex, age, underlying disease, BMI, stage, surgery method, postoperative time to discharge, and postoperative Medicare fees, from the Japanese administrative database associated with the Diagnosis Procedure Combination system. We classified patient BMIs as underweight (BMI<18.5 kg/m2), normal (BMI≥18.5 kg/m2 and <25 kg/m2) or overweight/obese (BMI≥25 kg/m2), then investigated the relationship between these categories and two postoperative outcomes: time to discharge and postoperative Medicare fees. The median postoperative time to discharge was 12 days in all patients, and 12 days in each of the three weight groups (p=0.62, n.s.). The median postoperative Medicare fees from surgery until discharge were (USD): all patients, $5,002; underweight, $5,875; normal weight, $4,797; and overweight/obese, $5,179 (p=0.146, n.s.). A multivariate analysis with adjustment for competing risk factors revealed that BMI was not associated with increased risk of longer postoperative time to discharge (normal weight: HR 1.17, p=0.29; overweight/obese: HR 1.17, p=0.37) or higher postoperative Medicare fees (OR 0.99, p=0.86, n.s.). Thus, high BMI was not found to be a factor for poor postoperative outcomes in Japanese patients with gallbladder cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Clitoral Blood Flow Changes after Surgery with Tension-Free Vaginal Mesh for Pelvic Organ Prolapse 21 27 EN Yuko Oiwa Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayano Ishii Integrated Support Center for Patients and Self-learning, Okayama University Hospital Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miyabi Inoue Miyabi Urogyne Clinic Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56455 We measured basal clitoral blood flow by Doppler sonography to determine whether tension-free vaginal mesh(TVM) affects the clitoral blood flow and sexual function in women with pelvic organ prolapse (POP). We performed a prospective study of 22 patients who underwent TVM for POP. Clitoral blood flow was measured by Doppler ultrasound. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) of the clitoral arteries were measured preoperatively and at 1, 3, and 6 months postoperatively. Female sexual function was also investigated with the Female Sexual Function Index (FSFI). The mean PI and RI were increased at 1 month and significantly decreased at 6 months postoperatively (p<0.05). In contrast, the mean PSV and EDV decreased at 1 month postoperatively and increased at 6 months postoperatively. These four parameters recovered to baseline levels at 6 months following surgery. Total FSFI scores improved significantly from 10.2±7.9 at baseline to 18.2±8.9 at 6 months postoperatively. Color Doppler ultrasonography is potentially useful in measuring clitoral blood flow in patients treated with TVM for POP. Prospective long-term studies are needed to evaluate the utility of this modality as a diagnostic and prognostic tool for female sexual dysfunction. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 The Role of Kallikrein-Related Peptidases in Atopic Dermatitis 1 6 EN Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56452 Excessive protease activity is a characteristic abnormality that affects the epidermal barrier in patients with atopic dermatitis (AD). Kallikrein-related peptidases (KLKs) are excessively expressed in AD lesions, and it is suggested that the abnormal action of KLKs is involved in the skin barrier dysfunction in AD. In other words, overexpressed KLKs disrupt the normal barrier function, and due to that breakdown, external substances that can become antigens of AD easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines. Further investigations are required to elucidate the role of KLKs in AD; this knowledge could contribute to the design of new therapeutic and prophylactic drugs for AD. No potential conflict of interest relevant to this article was reported.

International Speech Communication Association Acta Medica Okayama 1990-9772 2018 Naturalness Improvement Algorithm for Reconstructed Glossectomy Patient's Speech Using Spectral Differential Modification in Voice Conversion 2464 2468 EN Hiroki Murakami Sunao Hara Graduate School of Natural Science and Technology, Okayama University Masanobu Abe Graduate School of Natural Science and Technology, Okayama University Masaaki Sato Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shogo Minagi Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University In this paper, we propose an algorithm to improve the naturalness of the reconstructed glossectomy patient's speech that is generated by voice conversion to enhance the intelligibility of speech uttered by patients with a wide glossectomy. While existing VC algorithms make it possible to improve intelligibility and naturalness, the result is still not satisfying. To solve the continuing problems, we propose to directly modify the speech waveforms using a spectrum differential. The motivation is that glossectomy patients mainly have problems in their vocal tract, not in their vocal cords. The proposed algorithm requires no source parameter extractions for speech synthesis, so there are no errors in source parameter extractions and we are able to make the best use of the original source characteristics. In terms of spectrum conversion, we evaluate with both GMM and DNN. Subjective evaluations show that our algorithm can synthesize more natural speech than the vocoder-based method. Judging from observations of the spectrogram, power in high-frequency bands of fricatives and stops is reconstructed to be similar to that of natural speech. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 19326203 13 2 2018 Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment e0191109 EN Takanori Eguchi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Chiharu Sogawa Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuka Okusha Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kenta Uchibe Department of Oral Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryosuke Iinuma JSR Life Sciences Corporation Kisho Ono Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keisuke Nakano Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Jun Murakami Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Manabu Itoh JSR Life Sciences Corporation Kazuya Arai JSR Life Sciences Corporation Toshifumi Fujiwara Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuri Namba Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshiki Murata Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazumi Ohyama Radio Isotope Research Center, Okayama University Dental School Manami Shimomura Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hirohiko Okamura Department of Oral Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Tetsuya Nakatsura Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Kenichi Kozaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kuniaki Okamoto Department of Dental Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0006291X 2018 Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition EN Toshifumi Fujiwara Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Eguchi Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chiharu Sogawa Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kisho Ono Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Murakami Department of Oral Diagnosis and Dent-maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun-ichi Asaumi Department of Oral Diagnosis and Dent-maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kuniaki Okamoto Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Ken-ichi Kozaki Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance. 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 8 2018 Trends in Research Concerning School Re-entry Support for Children with Chronic Illness 181 191 EN Rie Murakami Division of Special Education, Faculty of Education Okayama University Division of Special Education, Faculty of Education Okayama University 10.18926/CTED/55817 The principle aim of the present study was to elucidate research trends and issues related to school re-entry. We reviewed past studies concerning school re-entry support for children with chronic illness. A total of 36 papers were analyzed for the keywords of "school re-entry," "support," "pediatric cancer," and "chronic illness." The results revealed that the concerns regarding the children and school re-entry support roles of legal guardians, healthcare providers, teachers, etc., and specific examples of collaboration with other occupations. "Guaranty a right to learn " and "relationship maintenance" were noted as issues, and ensuring a system that can establish certain learning opportunities even if the enrollment status of the child changes, continued maintenance of relationships of the patient before the onset of disease, and support to maintain the relationship of healthcare providers and teachers who are involved after onset of the disease are necessary even after school re-entry. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 3 2017 平成28年度岡山医学会賞 総合研究奨励賞（結城賞） 159 161 EN Kazutoshi Murakami Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 6 2017 Effects of (−)-epigallocatechin-3-gallate on EGFR- or Fusion Gene-driven Lung Cancer Cells 505 512 EN Yoshihiro Honda Department of Allergy and Respiratory Medicine, Okayama University Hospital Nagio Takigawa Department of Allergy and Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Takashi Ninomiya Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshio Kubo Department of Allergy and Respiratory Medicine, Okayama University Hospital Nobuaki Ochi Department of Allergy and Respiratory Medicine, Okayama University Hospital Masayuki Yasugi Department of Allergy and Respiratory Medicine, Okayama University Hospital Toshi Murakami Department of Allergy and Respiratory Medicine, Okayama University Hospital Hiromichi Yamane General Internal Medicine 4, Kawasaki Medical School Mitsune Tanimoto Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Original Article 10.18926/AMO/55587 (−)-Epigallocatechin-3-gallate (EGCG) has been shown to bind to several receptors including epidermal growth factor receptor (EGFR). EGFR tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK) inhibitors are effective for non-small cell lung cancers harboring activating EGFR mutations and ALK or c-ros oncogene 1 (ROS1) fusion genes, respectively. We investigated the effects of EGCG on EGFR- or fusion gene-driven lung cancer cells such as PC-9, RPC-9, H1975, H2228 and HCC78. The five cell lines had similar sensitivity to EGCG. Phosphorylated (p)EGFR, pAkt and pErk in PC-9, RPC-9 and H1975 cells were suppressed by EGCG (50 or 100 μM). EGCG also inhibited pALK in H2228, pROS1 in HCC78, and pErk and pAkt in both cell lines. All the xenograft tumors established using the 5 cell lines in EGCG-treated groups were significantly smaller than the tumors in the vehicle-treated groups. The numbers of tumor blood vessels of xenograft tissues in EGCG-treated mice were significantly lower than those in vehicle-treated mice. In conclusion, EGCG may be effective for EGFR-driven lung tumors irrespective of the presence of T790M, and for ALK or ROS1 fusion gene-driven lung tumors. 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 7 2017 出生前診断に関する大学生の意識および知識に関する調査 193 202 EN Rie Murakami Division of Special Education, Faculty of Education Okayama University Munehisa Yoshitoshi Division of Special Education, Faculty of Education Okayama University Akitaka Nakaya Division of Special Education, Faculty of Education Okayama University 10.18926/CTED/54945 　本研究では、出生前診断に対する大学生の意識および知識に関する動向を明らかにすることを目的とした。大学生171名を対象に、出生前診断を積極的に行っていくことや、自分自身が受けることに対する意識、関連する知識などについての調査を行った。その結果、意識に関する質問では「積極的実施」「自身の受検」「中絶実施」において、知識に関する質問では「意義理解」「メリット/デメリットの理解」「目的理解」「情報の把握」において、「どちらともいえない」と回答した者が多かった。このことから、出生前診断は割り切ることのできない感情的葛藤をともなう問題であると同時に、対象者らは判断する情報を持っていないためにこのように回答したのではないかと思われ、自身の考えを深めたり、正しい知識に基づいた選択を促したりするために、教育が重要であることが示唆された。 No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 129 1 2017 骨盤臓器脱に対するTVM 手術前後の性機能に関する検討 17 22 EN Yuko Matsumoto Department of Urology, Okayama University Graduate School of Medicne, Dentistry and Pharmaceutical Sciences We prospectively assessed sexual function before and after a tension-free vaginal mesh ( TVM) procedure for pelvic organ prolapse ( POP) . From April 2007 to March 2009, a total of 42 patients, who reported having an active sex life preoperatively underwent TVM for POP. Female sexual function was evaluated with the self-reporting, multiple-domain Female Sexual Function Index (FSFI) . We administered the FSFI to all of the patients before and at 3, 6, and 12 months after surgery. The mean age at surgery was 61.3±7.1 years. Before the TVM surgery, the FSFI score was very low ( 12.5±9.0) . The total FSFI score was improved significantly at 12 months after surgery ( 17.4±7.7) . The Arousal, Lubrication and Orgasm domains were significantly improved at 12 months after surgery. POP appears to have a significant negative impact on female sexual function. Our findings indicate that TVM for POP improved sexual function in a group of Japanese women with POP. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 5 2016 A Single-center, Open-label, Randomized Controlled Clinical Trial to Evaluate the Efficacy and Safety of the Indirect Bonding Technique 413 416 EN Takashi Murakami Department of Orthodontics, Okayama University Hospital Noriaki Kawanabe Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoki Kataoka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Hoshijima Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Komori Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuro Fujisawa Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Kamioka Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Clinical Study Protocols 10.18926/AMO/54604 Although accurate bracket placement is essential for orthodontic treatment, many practitioners apply brackets indiscriminately with direct or indirect bonding techniques. Nonetheless, there have been few prospective clinical comparisons of the 2 techniques. We will therefore conduct a single-center, randomized control trial in 100 patients aged &ge;12 years and diagnosed with malocclusion. All patients will receive orthodontic treatment using brackets with direct or indirect bonding techniques. The primary endpoints will be the total treatment time, occlusal index, discomfort at bonding, and oral hygiene after bonding. This study will clarify whether indirect bonding can improve the efficiency of orthodontic treatment. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 アディポカイン「バスピン」の同定とメタボリックシンドロームにおける意義 103 109 EN Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 平成27年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 99 102 EN Hiromichi Dansako Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 平成27年度岡山医学会賞 総合研究奨励賞（結城賞） 91 94 EN Ai Kajita Department of Dermatology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 2 2016 Diminished Gastric Resection Preserves Better Quality of Life in Patients with Early Gastric Cancer 119 130 EN Hiroshi Isozaki Sasau Matsumoto Shigeki Murakami Takehiro Takama Tatuo Sho Kiyohiro Ishihara Kunihiko Sakai Masanori Takeda Koji Nakada Toshiyoshi Fujiwara Original Article 10.18926/AMO/54191 Using the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45, we compared the surgical outcomes and the quality of life (QOL) between patients undergoing limited gastrectomies and those undergoing conventional gastrectomies. In Oomoto Hospital between January 2004 and December 2013, a total of 124 patients who met the eligibility criteria were enrolled. Using the main outcome measures of PGSAS-45, we compared 4 types of limited gastrectomy procedures (1/2 distal gastrectomy [1/2DG] in 21 patients; pylorus-preserving gastrectomy [PPG] in 15 patients; segmental gastrectomy [SG] in 26 patients; and local resection [LR] in 13 patients) with conventional gastrectomy (total gastrectomy [TG] in 24 patients and 2/3 or more distal gastrectomy [WDG] in 25 patients). The TG group showed the worst QOL in almost all items of the main outcome measures. The 1/2DG, PPG, and SG groups showed better QOL than the WDG group in many of the main outcome measures, including the body weight ratio, total symptom score, ingested amount of food per meal, and the dissatisfaction for daily life subscale. The LR group showed a better intake of food than the 1/2DG, PPG, and SG groups. The body weight ratio of the LR group was better than that of the SG group. Diminished gastric resection preserved better QOL in patients with early gastric cancer. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 1 2016 Helicobacter pylori 感染診療の現況と展望 13 19 EN Hiroyuki Okada No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice EN Ikuo Murakami No potential conflict of interest relevant to this article was reported.

PUBLIC LIBRARY SCIENCE Acta Medica Okayama 1932-6203 9 3 2014 Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy e92647 EN Mayu Watanabe Atsuko Nakatsuka Kazutoshi Murakami Kentaro Inoue Takahiro Terami Chigusa Higuchi Akihiro Katayama Sanae Teshigawara Jun Eguchi Daisuke Ogawa Eijiro Watanabe Jun Wada Hirofumi Makino Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver. Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER) stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in mice to explore the therapeutic impact of Pemt on the progression of diabetic nephropathy and diabetes, which was induced by the injection of streptozotocin (STZ). Although the blood glucose levels were similar in STZ-induced diabetic Pemt+/+ and Pemt−/−mice, the glomerular hypertrophy and albuminuria in Pemt−/− mice were significantly reduced. Pemt deficiency reduced the intraglomerular F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial fibrosis and tubular atrophy. The expression of glucose-regulated protein-78 (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells, the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased the expression of GRP78, which was reduced by transfection of a shRNA lentivirus for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was significantly reduced in Pemt−/− diabetic mice, and shRNA-Pemt upregulated the phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24 cells. Taken together, these findings indicate that the inhibition of Pemt activity ameliorates the ER stress associated with diabetic nephropathy in a model of type 1 diabetes and corrects the functions of the three major pathways downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 6 2016 Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis 21721 EN Atsuko Nakatsuka Makoto Matsuyama Satoshi Yamaguchi Akihiro Katayama Jun Eguchi Kazutoshi Murakami Sanae Teshigawara Daisuke Ogawa Nozomu Wada Tetsuya Yasunaka Fusao Ikeda Akinobu Takaki Eijiro Watanabe Jun Wada 　Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N-methyltransferase (PEMT) is a risk for the lean NASH. The Pemt−/− mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt−/− mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4α resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 5 2015 Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis 16920 EN Akihiro Katayama Atsuko Nakatsuka Jun Eguchi Kazutoshi Murakami Sanae Teshigawara Motoko Kanzaki Tomokazu Nunoue Kazuyuki Hida Nozomu Wada Tetsuya Yasunaka Fusao Ikeda Akinobu Takaki Kazuhide Yamamoto Hiroshi Kiyonari Hirofumi Makino Jun Wada Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 0028-0836 517 2015 Native structure of photosystem II at 1.95 Å resolution viewed by femtosecond X-ray pulses 99 103 EN Michihiro Suga Fusamichi Akita Kunio Hirata Go Ueno Hironori Murakami Yoshiki Nakajima Tetsuya Shimizu Keitaro Yamashita Masaki Yamamoto Hideo Ago Jian-Ren Shen Photosynthesis converts light energy into biologically useful chemical energy vital to life on Earth. The initial reaction of photosynthesis takes place in photosystem II (PSII), a 700-kilodalton homodimeric membrane protein complex which catalyses photo-oxidation of water into dioxygen through an S-state cycle of the oxygen evolving complex (OEC). The structure of PSII has been solved by X-ray diffraction (XRD) at 1.9-ångström (Å) resolution, which revealed that the OEC is a Mn4CaO5-cluster coordinated by a well-defined protein environment1. However, extended X-ray absorption fine structure (EXAFS) studies showed that the manganese cations in the OEC are easily reduced by X-ray irradiation2, and slight differences were found in the Mn–Mn distances between the results of XRD1, EXAFS3–7 and theoretical studies8–14. Here we report a ‘radiation-damage-free’ structure of PSII from Thermosynechococcus vulcanus in the S1 state at a resolution of 1.95 Å using femtosecond X-ray pulses of the SPring-8 ångström compact free-electron laser (SACLA) and a huge number of large, highly isomorphous PSII crystals. Compared with the structure from XRD, the OEC in the X-ray free electron laser structure has Mn–Mn distances that are shorter by 0.1–0.2 Å. The valences of each manganese atom were tentatively assigned as Mn1D(III), Mn2C(IV), Mn3B(IV) and Mn4A(III), based on the average Mn–ligand distances and analysis of the Jahn–Teller axis on Mn(III). One of the oxo-bridged oxygens, O5, has significantly longer Mn–O distances in contrast to the other oxo-oxygen atoms, suggesting that it is a hydroxide ion instead of a normal oxygen dianion and therefore may serve as one of the substrate oxygen atoms. These findings provide a structural basis for the mechanism of oxygen evolution, and we expect that this structure will provide a blueprint for design of artificial catalysts for water oxidation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 陽子線治療 155 157 EN Kuniaki Katsui Tomoaki Okimoto Susumu Kanazawa No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 平成26年度岡山医学会賞 胸部・循環研究奨励賞（砂田賞） 95 97 EN Koji Tokioka No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 2 2015 Complication of Chronic Eosinophilic Pneumonia in an Elderly Patient with Sjögren Syndrome 123 127 EN Koichi Waseda Hideharu Hagiya Yoshihisa Hanayama Tomohiro Terasaka Kosuke Kimura Takao Tsuzuki Kou Hasegawa Takahiro Nada Eri Nakamura Kazutoshi Murakami Eisei Kondo Fumio Otsuka Case Report 10.18926/AMO/53342 An 81-year-old Japanese male with primary Sjögren syndrome (pSS) developed a low-grade fever and productive cough which were refractory to antibiotic therapy. Based on the high level of eosinophils observed in his bronchial alveolar lavage, he was diagnosed with chronic eosinophilic pneumonia (CEP) and successfully treated by oral prednisolone. Interstitial lung diseases associated with pSS (pSS-ILDs) usually present as nonspecific interstitial pneumonia or usual interstitial pneumonia; therefore, the present case is extremely unique in that the patientʼs condition was complicated with CEP. A diagnosis of advanced gallbladder cancer was made in the patientʼs clinical course, suggesting the advisability of a whole-body workup in cases of pSS, especially in elderly patients. 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 5 2015 出生前診断に関する大学生の意識調査 149 156 EN Rie Murakami(Yokouchi) Munehisa Yoshitoshi 10.18926/CTED/53245 　本研究では，出生前診断に対する大学生の意識を明らかにすることを目的とした。大学生74 名を対象に，出 生前診断を積極的に行っていくことや，自分自身が受けることに対する意識，関連する知識などについての調査 を行った。その結果，「出生前診断を積極的に行っていくこと」については，「どちらとも言えない」と回答した 者が多く，生前診断のメリット，デメリットを理解した上でこのように回答した者が多いことが示された。一方， 「自分（またはパートナー）が出生前診断を受けること」については，賛成と回答した者が多く，診断に対する 関心の高さが伺えた。「出生前診断の結果に基づいて人工的中絶を行うこと」については，反対と回答した者が 多く，「命の選別をすることになるから」などの意見が見られた。「出生前診断に関する知識」については，検査 の実施方法や検査後について自身の知識が不十分であると認識している者が多いことが明らかとなった。最後に， 今後の実施をめぐる課題について論じた。 No potential conflict of interest relevant to this article was reported.

岡山大学経済学会 Acta Medica Okayama 0386-3069 46 2 2014 Akira Okamoto, Tax Policy for Aging Societies: Lessons from Japan（ Springer，2004） 255 261 EN Masako Murakami 10.18926/OER/53107 No potential conflict of interest relevant to this article was reported.

BioMed Central Ltd. Acta Medica Okayama 1472-6831 14 2014 Cross-cultural validity of a dietary questionnaire for studies of dental caries risk in Japanese EN Chikako Shinga-Ishihara Yukie Nakai Peter Milgrom Kaori Murakami Michiyo Matsumoto-Nakano Background: Diet is a major modifiable contributing factor in the etiology of dental caries. The purpose of this paper is to examine the reliability and cross-cultural validity of the Japanese version of the Food Frequency Questionnaire to assess dietary intake in relation to dental caries risk in Japanese. Methods: The 38-item Food Frequency Questionnaire, in which Japanese food items were added to increase content validity, was translated into Japanese, and administered to two samples. The first sample comprised 355 pregnant women with mean age of 29.2 +/- 4.2 years for the internal consistency and criterion validity analyses. Factor analysis (principal components with Varimax rotation) was used to determine dimensionality. The dietary cariogenicity score was calculated from the Food Frequency Questionnaire and used for the analyses. Salivary mutans streptococci level was used as a semi-quantitative assessment of dental caries risk and measured by Dentocult SM. Dentocult SM scores were compared with the dietary cariogenicity score computed from the Food Frequency Questionnaire to examine criterion validity, and assessed by Spearman's correlation coefficient (r(s)) and Kruskal-Wallis test. Test-retest reliability of the Food Frequency Questionnaire was assessed with a second sample of 25 adults with mean age of 34.0 +/- 3.0 years by using the intraclass correlation coefficient analysis. Results: The Japanese language version of the Food Frequency Questionnaire showed high test-retest reliability (ICC = 0.70) and good criterion validity assessed by relationship with salivary mutans streptococci levels (r(s) = 0.22; p < 0.001). Factor analysis revealed four subscales that construct the questionnaire (solid sugars, solid and starchy sugars, liquid and semisolid sugars, sticky and slowly dissolving sugars). Internal consistency were low to acceptable (Cronbach's alpha = 0.67 for the total scale, 0.46-0.61 for each subscale). Mean dietary cariogenicity scores were 50.8 +/- 19.5 in the first sample, 47.4 +/- 14.1, and 40.6 +/- 11.3 for the first and second administrations in the second sample. The distribution of Dentocult SM score was 6.8% (score = 0), 34.4% (score = 1), 39.4% (score = 2), and 19.4% (score = 3). Participants with higher scores were more likely to have higher dietary cariogenicity scores (p < 0.001; Kruskal-Wallis test). Conclusions: These results provide the preliminary evidence for the reliability and validity of the Japanese language Food Frequency Questionnaire. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 68 6 2014 Visualization of Astrocytic Primary Cilia in the Mouse Brain by Immunofluorescent Analysis Using the Cilia Marker Arl13b 317 322 EN Kyosuke Kasahara Ko Miyoshi Shinki Murakami Ikuko Miyazaki Masato Asanuma Original Article 10.18926/AMO/53020 In vertebrates, almost all somatic cells extend a single immotile cilium, referred to as a primary cilium. Increasing evidence suggests that primary cilia serve as cellular antennae in many types of tissues by sensing chemical or mechanical stimuli in the milieu surrounding the cells. In rodents an antibody to adenylyl cyclase 3 (AC3) has been widely used to label the primary cilia of neurons in vivo by immunostaining, whereas the lack of markers for the primary cilia of astrocytes has made it difficult to observe astrocytic primary cilia in vivo. Here, we obtained a visualization of astrocytic primary cilia in the mouse brain. In the somatosensory cortex, a large portion of neurons and astrocytes at postnatal day 10 (P10), and of neurons at P56 had AC3-positive primary cilia, whereas only approx. one-half of the astrocytes in the P56 mice carried primary cilia weakly positive for AC3. In contrast, the majority of astrocytes had ADP-ribosylation factor-like protein 13B (Arl13b)-positive primary cilia in the somatosensory cortex and other brain regions of P56 mice. The lengths of astrocytic primary cilia positive for Arl13b varied among the brain regions. Our data indicate that Arl13b is a noteworthy marker of astrocytic primary cilia in the brain. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1029-8428 26 3 2014 Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice 285 298 EN Shinki Murakami Ikuko Miyazaki Norio Sogawa Ko Miyoshi Masato Asanuma Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0014-4827 326 2 2014 Everolimus prolonged survival in transgenic mice with EGFR-driven lung tumors 201 209 EN Masayuki Yasugi Nagio Takigawa Nobuaki Ochi Kadoaki Ohashi Daijiro Harada Takashi Ninomiya Toshi Murakami Yoshihiro Honda Eiki Ichihara Mitsune Tanimoto Katsuyuki Kiura Everolimus is an orally administered mTOR inhibitor. The effect, and mechanism of action, of everolimus on lung cancers with an epidermal growth factor receptor (EGFR) mutation remain unclear. Four gefitinib-sensitive and -resistant cell lines were used in the present work. Growth inhibition was determined using the MTT assay. Transgenic mice carrying the EGFR L858R mutation were treated with everolimus (10 mg/kg/day), or vehicle alone, from 5 to 20 weeks of age, and were then sacrificed. To evaluate the efficacy of everolimus in prolonging survival, everolimus (10 mg/kg/day) or vehicle was administered from 5 weeks of age. The four cell lines were similarly sensitive to everolimus. Expression of phosphorylated (p) mTOR and pS6 were suppressed upon treatment with everolimus in vitro, whereas the pAKT level increased. The numbers of lung tumors with a long axis exceeding 1 mm in the everolimus-treated and control groups were 1.9 +/- 0.9 and 9.4 +/- 3.2 (t-test, p<0.001), respectively. pS6 was suppressed during everolimus treatment. Although apoptosis and autophagy were not induced in everolimus-treated EGFR transgenic mice, angiogenesis was suppressed. The median survival time in the everolimus-treated group (58.0 weeks) was significantly longer than that in the control group (31.2 weeks) (logrank test, p<0.001). These findings suggest that everolimus had an indirect effect on tumor formation by inhibiting angiogenesis and might be effective to treat lung tumors induced by an activating EGFR gene mutation. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2014 Neuroprotective Effects of Metallothionein Against Rotenone-induced Myenteric Neurodegeneration in Parkinsonian Mice EN Shinki Murakami No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 3 2014 アストロサイトによる神経機能修飾とパーキンソン病での神経保護 203 208 EN Masato Asanuma No potential conflict of interest relevant to this article was reported.