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Effective conservation of globally distributed marine species relies on identification of demographically independent populations to ensure that management actions are directed at the appropriate scale. This identification is particularly challenging for species with complex life histories when local breeding populations have not been adequately sampled. We used mtDNA to analyze the population structure of loggerhead turtles from a total of 555 samples collected from 12 nesting sites in Japan in the Northwest Pacific, including previously unsampled rookeries in the Ryukyu Archipelago, for a comprehensive coverage of the nesting distribution. We identified a total of 9 haplotypes based on 820 bp of the mtDNA control region, including 5 variants of a single previously described 380 bp haplotype. We discovered that 1 haplotype (CcP1.1) previously rare in the North Pacific is common in the Ryukyu Archipelago. Based on analysis of haplotype frequencies, we found significant differentiation among regionally grouped nesting populations (analysis of molecular variance p < 0.0001, df = 8; pairwise FST ranging from 0.033 to 0.145). Our results provide evidence to support the recognition of 3 management units (MU) within the NW Pacific Regional Management Unit (RMU). These include (1) the Ryukyu MU that includes Okinawa, Okinoerabu and Amami, (2) Yakushima Island MU and (3) a Mainland MU that includes Bousou, Enshu-nada, Shikoku, Kii and Eastern Kyushu. These new data from Japan will provide important baseline data for global genetic stock assessments and contribute to our understanding of the population structure, ecology and life history of this migratory marine species in the northern Pacific.

Kenta Hasumi,1,2 Yukihiro Yoshida,1 Masaya Yotsukura,1 Kazuo Nakagawa,1 Koichi Goto,2 Shun-ichi Watanabe1 1Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan; 2Department of Comprehensive Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanCorrespondence: Kenta Hasumi; Yukihiro Yoshida, Department of Thoracic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, Tel +81-3-3542-2511, Email khasumi@ncc.go.jp; yukiyosh@ncc.go.jpBackground: This study investigated perioperative clinical information, surgical findings, and postoperative courses of patients who underwent reoperation due to bleeding after the surgery for pulmonary malignancies.Methods: We identified patients who underwent reoperation due to postoperative bleeding from 6989 patients who had had operations for pulmonary malignancies between January 2007 and July 2019. Data were retrospectively collected from medical charts.Results: Twenty-two patients (0.3%) underwent reoperation for hemostasis. The reason for reoperation was a shock state with minimum systolic blood pressure < 90 mm Hg in 12 patients (55%), persistent bloody drainage of 100 mL/h or more in 15 patients (68%), and intrathoracic hematoma on a chest X-ray image in 14 patients (64%). All those three findings were observed in five patients (23%), two in nine patients (41%), and one in eight patients (36%). The source of bleeding could not be identified during reoperation in four patients (18%). In the regression analysis, the coefficient of determination between the amount of drainage from a chest drain and the volume of intrathoracic hematoma found during reoperation was 0.31, indicating poor correlation. Postoperative complications and death occurred in two (9%) and zero patients, respectively.Conclusion: Reoperation due to bleeding is required in certain cases. The amount of drainage from a chest drain does not necessarily reflect the volume of intrathoracic hematoma and it is hard to estimate the total amount of bleeding. The decision to perform reoperation for hemostasis should be comprehensively made on the basis of clinical signs and chest X-ray findings.Keywords: bleeding, hemostasis, lung neoplasms, thoracic surgery, intraoperative complications, reoperation

Keisuke Noto,1 Akihito Suzuki,1 Toshinori Shirata,1 Yoshihiko Matsumoto,1 Nana Takahashi,1 Kaoru Goto,2 Koichi Otani1 1Department of Psychiatry, Yamagata University School of Medicine, Yamagata 990-9585, Japan; 2Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, JapanCorrespondence: Toshinori Shirata Email white_gregory000@yahoo.co.jpPurpose: Attachment research shows that attachment experiences with parents in childhood influence the characterization of personality traits. Meanwhile, it is known that mu-opioid receptor function is involved in human attachment. Furthermore, a few studies suggest that the A118G polymorphism of the mu-opioid receptor gene (OPRM1) is associated with altered mu-opioid receptor function. Thus, we examined if the OPRM1 polymorphism moderates the sensitivity to parental behaviors and thereby contributes to the characterization of personality traits.Materials and Methods: Participants were 725 healthy Japanese. Parenting practices of their parents were evaluated by the Parental Bonding Instrument (PBI) with the care and protection subscales. Personality was evaluated using the Temperament and Character Inventory (TCI). The OPRM1 A118G polymorphism was detected by a PCR method.Results: Multiple regression analyses revealed significant effects of the interaction between the OPRM1 genotype and maternal protection on scores of the self-directedness and cooperativeness dimensions, while significant main effects of the OPRM1 genotype on scores of the TCI were not found. Further analyses showed that there were significant negative correlations between maternal protection scores and the two dimensional scores in the A/A and A/G genotypes with higher correlation coefficients in the former, but not in the G/G genotype.Conclusion: The present study suggests that the OPRM1 polymorphism contributes to the characterization of personality traits by moderating the sensitivity to parental behaviors, especially maternal protection.Keywords: OPRM1, attachment, personality, PBI, TCI, gene–environment interaction

Toshinori Shirata,1 Akihito Suzuki,1 Yoshihiko Matsumoto,1 Keisuke Noto,1 Kaoru Goto,2 Koichi Otani1 1Department of Psychiatry, Yamagata University School of Medicine, Yamagata 990-9585, Japan; 2Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, JapanCorrespondence: Toshinori Shirata Email white_gregory000@yahoo.co.jpPurpose: It is suggested that increased methylation of the brain-derived neurotrophic factor (BDNF) gene is involved in the pathogenesis of depression, while sociotropy and autonomy are proposed as personality vulnerability factors in cognitive model of depression. We examined the interrelation between BDNF gene methylation and sociotropy or autonomy, with taking into account the previously reported deleterious effect of parental overprotection on sociotropy. Materials and Methods: The participants consisted of 90 healthy Japanese volunteers. Methylation levels of the BDNF gene in peripheral blood were quantified by bisulfite pyrosequencing. Sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale, and perceived parental protection was evaluated by the Parental Bonding Instrument.Results: In Pearson’s correlation analysis, there was a positive correlation between methylation levels of the BDNF gene and sociotropy scores (p< 0.05) but not autonomy scores, and a positive correlation between maternal protection scores and sociotropy scores (p< 0.05). In structural equation modeling, two models were proposed; the first one is that hypermethylation of the BDNF gene and maternal overprotection independently contribute to high sociotropy, and the second one is that maternal overprotection contributes to high sociotropy which then leads to hypermethylation of the BDNF gene.Conclusion: The present study suggests an interrelation between increased BDNF gene methylation and high sociotropy.Keywords: autonomy, BDNF gene, methylation, parental protection, sociotropy

Kentaro Nakanishi,1 Kenji Goto,1 Kanako Kondo,1,2 Keiichi Hiramoto,1 Kazuya Ooi1 1Department of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan; 2Department of Pharmacy, Kuwana City Medical Center, Kuwana, Mie 511-0061, JapanCorrespondence: Kazuya OoiDepartment of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, JapanEmail zooi@suzuka-u.ac.jpBackground: Vitamin C plays a part in various roles in the human body. In this study, we examined the effect of oral administration of high-dose vitamin C on the skin dryness induced by irinotecan.Methods: To establish the experimental model of irinotecan-induced skin dryness, the drug was intraperitoneally administered for four consecutive days. Simultaneously, oral administration of high-dose vitamin C (4 g/kg) was continued for 4 days.Results: High-dose vitamin C administration ameliorated the skin dryness induced by irinotecan. The expression of caspase-3 and caspase-9, reactive oxygen species, and the number of TUNEL-positive cells increased in the skin of irinotecan-treated mice but were lowered by high-dose vitamin C administration. In contrast, fibroblasts and collagen type I decreased in the skin of the irinotecan-treated mice but was increased by high-dose vitamin C administration.Conclusion: These results suggested that high-dose vitamin C administration can improve the skin dryness induced by irinotecan.Keywords: apoptosis, collagen type I, irinotecan, reactive oxygen species, vitamin C

Yutaka Kuroda, Toshiyuki Kawai, Koji Goto, Shuichi Matsuda Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan Abstract: Corticosteroids have been widely used for the treatment of various inflammatory diseases because they provide an acute response of immunosuppression. Numerous side effects of corticosteroids have also been known, with varying degrees of severity. Osteonecrosis of the femoral head (ONFH) is a rare and serious complication that directly inhibits walking because of femoral head collapse. However, sometimes, clinicians who consider that corticosteroids are required for primary disease do not recognize steroid-induced ONFH. The final stage of ONFH is severe osteoarthritis, requiring total hip arthroplasty. We describe a 23-year-old woman with bilateral ONFH after corticosteroid treatment for alopecia areata (AA). She was administered several intralesional corticosteroid injections to the scalp and repeated systemic corticosteroid therapy for extensive AA. While undergoing therapy, she lost her balance and complained of right groin pain when standing. The patient was subsequently diagnosed with bilateral ONFH. She recovered from AA, but she complained of persistent right hip pain, which subsequently required total hip arthroplasty. We would like to emphasize that patients on corticosteroid therapy for any common disease should be considered as having a potential risk for ONFH. An early stage detection of ONFH is crucial for its treatment. MRI evaluation warrants a higher level of accuracy in early diagnosis of ONFH for the opportunity to undergo joint-preservation surgery in patients with ONFH. Keywords: osteonecrosis, femoral head, alopecia areata, avascular necrosis, steroid, case report

Toshinori Shirata,1 Akihito Suzuki,1 Yoshihiko Matsumoto,1 Nana Takahashi,1 Keisuke Noto,1 Kaoru Goto,2 Koichi Otani1 1Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan; 2Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata, Japan Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has an important function in neuroplasticity and neuronal development. It is suggested that increased methylation of the BDNF gene resulting in decreased BDNF activity is associated with depression. Meanwhile, neuroticism is a well-known risk factor for developing depression. In the present study, the relationship between methylation of the BDNF gene and personality traits including neuroticism was examined. Subjects and methods: The subjects were 98 healthy Japanese. Methylation levels of the BDNF gene were determined by the bisulfite-pyrosequencing method. Personality traits including neuroticism were assessed by the NEO Personality Inventory-Revised. Results: There was a positive correlation between neuroticism scores and methylation levels of the BDNF gene. The subjects with higher neuroticism scores had higher levels of BDNF gene methylation compared with those with lower neuroticism scores. Meanwhile, other personality traits were not associated with BDNF gene methylation. Conclusion: The present study suggests that high neuroticism is related to increased methylation of the BDNF gene. Keywords: BDNF, depression, epigenetics, methylation, neuroticism

Kenichi Goto,1,2 Emiko Ogawa,1,3 Kaoruko Shimizu,4 Hironi Makita,4 Hidenobu Suzuki,5 Yoshiki Kawata,5 Noboru Niki,5 Masaharu Nishimura,4 Yasutaka Nakano1 1Division of Respiratory Medicine, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, 2Department of Pulmonary Medicine, Takatsuki Red Cross Hospital, Takatsuki, Osaka, 3Health Administration Center, Shiga University of Medical Science, Otsu, Shiga, 4First Department of Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, 5Institute of Technology and Science, Tokushima University, Tokushima, Tokushima, Japan Background: Osteoporosis is a well-known comorbidity in COPD. It is associated with poor health status and prognosis. Although the exact pathomechanisms are unclear, osteoporosis is suggested to be either a comorbidity due to shared risk factors with COPD or a systematic effect of COPD with a cause–effect relationship. This study aimed to evaluate whether progression of osteoporosis is synchronized with that of COPD. Materials and methods: Data from 103 patients with COPD included in the Hokkaido COPD cohort study were analyzed. Computed tomography (CT) attenuation values of thoracic vertebrae 4, 7, and 10 were measured using custom software, and the average value (average bone density; ABD4,7,10) was calculated. The percentage of low attenuation volume (LAV%) for each patient was also calculated for evaluation of emphysematous lesions. Annual change in thoracic vertebral CT attenuation, which is strongly correlated with dual-energy X-ray absorptiometry-measured bone mineral density, was compared with that in FEV1.0 or emphysematous lesions. Results: In the first CT data set, ABD4,7,10 was significantly correlated with age (ρ=–0.331; p=0.0006), body mass index (BMI; ρ=0.246; p=0.0136), St George’s Respiratory Questionnaire (SGRQ) activity score (ρ=–0.248; p=0.0115), eosinophil count (ρ=0.229; p=0.0198), and LAV% (ρ=–0.372; p=0.0001). However, ABD4,7,10 was not associated with FEV1.0. After adjustment for age, BMI, SGRQ activity score, and eosinophil count, no significant relationship was found between ABD4,7,10 and LAV%. Annual change in ABD4,7,10 was not associated with annual change in LAV% or FEV1.0. Conclusion: Progression of osteoporosis and that of COPD are not directly related or synchronized with each other. Keywords: osteoporosis, quantitative CT analysis, FEV1.0, low attenuation volume, automatic analysis, systemic effect