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Summary: We evaluated the secondary fracture prevention in 1445 patients with distal radius fracture by trauma surgeons. The rate of patients with distal radius fracture who underwent bone mineral density (BMD) examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present. Introduction: To clarify the status of osteoporosis interventions after distal radial fractures by trauma surgeons who play the main role in treatment for these fractures, we performed a survey involving multiple institutions in Japan. Methods: We asked 155 board members of the Japanese Society for Fracture Repair for their cooperation and performed a survey in 48 institutions with which members who gave cooperation were affiliated. The subjects consisted of consecutive patients with distal radial fractures occurring between January and December 2012. The presence or absence of a diagnosis of osteoporosis and bone mineral density examination after fracture was investigated. Results: A total of 1445 patients with distal radial fractures were evaluated in this study. BMD examination for diagnosis and treatment for osteoporosis after fracture was performed respectively in 126 (8.7 %) and 193 (13.4 %) of 1445 patients. Treatment for osteoporosis was performed in 93 (73.8 %) of 126 patients who underwent BMD examination after fracture and 100 (8.2 %) of 1219 who did not undergo BMD examination. Of the 126 patients who underwent BMD examination after fracture, 89 showed a BMD <80 % of the young adult mean as a criterion for the initiation of drug treatment for osteoporosis in Japan and 77 (86.5 %) of the 89 patients were treated with drugs. Conclusions: The rate of patients with distal radial fractures who underwent BMD examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present. [ABSTRACT FROM AUTHOR]

AbstractThe attitudes towards body weight and shape, desire for thinness and dieting behaviours were investigated in pre-adolescent and adolescent girls and boys (547 elementary school students, 615 junior high school students, and 470 senior high school students) aged 10–17 years in Osaka Prefecture, Japan, by a self-report questionnaire. Forty-eight per cent of 10-year-old females and 84% of 17-year-old females categorized themselves as ‘fat’ or ‘too fat’. The fear of weight gain and desire for thinness was reported in 35% and 51% of 10-year-old girls, respectively, and increased progressively with ageing to 79% and 87% of 17-year-old girls. In contrast, these were reported by 20–30% of boys in the corresponding age groups. Some practices to be slim were found in 22% of the 10-year-old girls, and increased to 37% among the 17-year-old girls, whereas they were found in around 20% of the boys at each age. The practices to be slim were found in 32% of the girls who were 85–90% of the standard body weight (SBW) and in 14% of the girls less than 85% of the SBW. These results suggest that significant concerns about weight and shape and dieting behaviours are present in young Japanese girls and increase progressively with age. These results are compatible with those in Western society. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate standards of large-for-gestational-age (LGA) infants of twin pregnancies based on the incidence of neonatal hypoglycemia. We examined 277 dichorionic twin infants (in 201 dichorionic twin pregnancies) who were delivered weighing > or = 2,500 g at 37-41 weeks of gestation. LGA in twin pregnancies was identified when the infant deviated > by 1.5SD from the mean gestational age of this study (LGA based on the twin pregnancy standard), or when the infant deviated by >1.5 SD of the intrauterine growth curve of Japanese (LGA based the singleton pregnancy standard). Using the twin pregnancy standard, the incidence of neonatal hypoglycemia in LGA twin infants was not measurably different from that in appropriate-for-gestational-age (AGA). However, using the singleton pregnancy standard, the incidence of neonatal hypoglycemia was significantly higher than that in AGA infants. In conclusion, LGA in twin pregnancies should be studied based on the singleton pregnancy standard to assess the incidence of neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

Investigates gender and diseases in Japan. Reference to a survey of the National Institute of Population and Social Security Research on the expectation of parents on the gender of children; Investigation of gender differences in disease severity; Reasons behind gender differences.

Objectives: This study aimed to clarify the issues related to pregnancy in patients with inflammatory rheumatic diseases (RDs) and to provide useful information for developing medical services from patients' perspectives., Methods: A survey involving approximately 5000 members of the Patients Association for Collagen Vascular Diseases Japan was conducted using a questionnaire that was sent and returned by mail. The questionnaire items included age at the time of the survey, types of RDs, association of RDs with pregnancy/childbirth outcomes, and pregnancy-related supports and hindrances., Results: We received 491 completed questionnaires. The most common RD was systemic lupus erythematosus (n = 309). Approximately 60% of participants had a history of childbirth. Approximately 60% of participants had previously experienced pregnancy-related challenges due to RDs. These included concerns about the influence of drugs on babies, genetic transmission, and active disease. Patients with active disease at the time of conception were more likely to experience disease exacerbation during pregnancy, but this did not correlate with whether the pregnancy was planned., Conclusion: This study revealed that many patients with RDs experienced pregnancy-related challenges and needed appropriate support based on appropriate information. The findings here should help rheumatologists, healthcare providers, and public agencies provide counselling and information., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Adolescents and young adults (AYAs) represent a small proportion of patients with cancer. The genomic profiles of AYA patients with cancer are not well-studied, and outcomes of genome-matched therapies remain largely unknown., Patients and Methods: We investigated differences between Japanese AYA and older adult (OA) patients in genomic alterations, therapeutic evidence levels, and genome-matched therapy usage by cancer type. We also assessed treatment outcomes., Results: AYA patients accounted for 8.3% of 876 cases. Microsatellite instability-high and/or tumor mutation burden was less common in AYA patients (1.4% versus 7.7% in OA; P = 0.05). However, BRCA1 alterations were more common in AYA patients with breast cancer (27.3% versus 1.7% in OA; P = 0.01), as were MYC alterations in AYA patients with colorectal cancer (23.5% versus 5.8% in OA; P = 0.02) and sarcoma (31.3% versus 3.4% in OA; P = 0.01). Genome-matched therapy use was similar between groups, with overall survival tending to improve in both. However, in AYA patients, the small number of patients prevented statistical significance. Comprehensive genomic profiling-guided genome-matched therapy yielded encouraging results, with progression-free survival of 9.0 months in AYA versus 3.7 months in OA patients (P = 0.59)., Conclusion: Our study suggests that tailored therapeutic approaches can benefit cancer patients regardless of age., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: For women, being underweight increases their susceptibility to osteoporosis, anemia, and other conditions and affects the weight of their infants and the well-being of future generations. This study examined the association between low pre-pregnancy body mass index (BMI) and low birthweight using health insurance claims data and health checkup data, including weight measurements., Methods: We used health insurance claims data and health checkup data (JMDC, Tokyo, Japan) of women and their newborns in Japan between 2006 and 2020. We used checkup data, which included more accurate weight measurements and blood test-based diagnoses of anemia and hyperlipidemia compared to self-reported data. Maternal pre-pregnancy BMI was compared across three groups: underweight (BMI <18.5 kg/m 2 ), normal weight (BMI 18.5-24.9 kg/m 2 ), and overweight (BMI ≥25.0 kg/m 2 ). The primary outcome was low birthweight (<2500 g), and secondary outcome was preterm childbirth. Logistic regression analyses were conducted to compare outcomes in the three groups by BMI. The underweight BMI group was considered as the reference group. A subgroup analysis was performed by maternal age., Results: In total, 16 363 mothers (underweight, 3418 [21%], normal weight, 11 493 [70%], and overweight, 1452 [8.9%]) were included. The risk of primary outcome (low birthweight) was significantly lower in the normal weight group than in the underweight group (4.6% vs. 5.7%; adjusted odds ratio 0.78 [95% confidence interval: 0.65-0.96]). In the subgroup analyses, no significant differences were noted in the incidences of low birthweight and preterm childbirth between maternal age groups., Conclusions: Pre-pregnancy BMI was associated with an increased risk of delivering low-birthweight infant. Awareness about the importance of women's pre-pregnancy health and appropriate BMI may reduce the incidence of low birthweight., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background: Trastuzumab has improved breast cancer (BC) prognosis and reduced anthracycline use. However, the characteristic changes of anthracycline-related cardiomyopathy (ARCM) in patients with BC remain unclear. We aimed to update our understanding of ARCM in the trastuzumab era., Methods: This retrospective observational cohort study included 2959 patients with BC treated with anthracyclines at three regional cancer centers in Niigata City between 1990 and 2020. Seventy-five patients (2.5%) developed ARCM and were categorized into two groups: pre- 2007 (early phase) and post-2007 (late phase), corresponding to before and during the trastuzumab era in Japan., Results: ARCM incidence peaked at 6% in the 1990s, then decreased and stabilized at 2% until the 2010s. Survivors of anthracycline-treated BC increased more rapidly in the late phase, with four times as many patients with ARCM compared to the end of the early phase (26 and six, respectively). Although the rate of change in accumulation from the early phase to the late phase was slight in the anthracycline-treated BC group, it was more pronounced in the ARCM group (P < 0.001). Mean anthracycline use in the late phase was significantly lower than in the early phase (307 vs. 525 mg/m 2 , P < 0.001). Five-year survival rates in the late phase tended to be higher than early phase (45% and 28%, respectively. P = 0.058). Human epidermal growth factor receptor type 2 (HER2) positivity with trastuzumab therapy in the late phase was an independent predictor for mortality within 10 years (hazard ratio = 0.24, 95% confidence interval: 0.10-0.56; P = 0.001)., Conclusions: HER2-positive patients with ARCM receiving trastuzumab therapy had a better prognosis than HER2-positive and HER2-negative patients with ARCM not receiving trastuzumab therapy, and this trend has been increasing in the trastuzumab era. These findings highlight the importance of HER2-targeted treatments in improving prognosis for BC patients with ARCM., (© 2024. The Author(s).)

Background: Medical care and long-term care utilization in the last year of life of frail older adults could be a key indicator of their quality of life. This study aimed to identify the medical care expenditure (MCE) trajectories in the last year of life of frail older adults by investigating the association between MCE and long-term care utilization in each trajectory., Methods: The retrospective cohort study of three municipalities in Japan included 405 decedents (median age at death, 85 years; 189 women [46.7%]) from a cohort of 1,658 frail older adults aged ≥65 years who were newly certified as support level in the long-term care insurance program from April 2012 to March 2013. This study used long-term care and medical insurance claim data from April 2012 to March 2017. The primary outcome was MCE over the 12 months preceding death. Group-based trajectory modeling was conducted to identify the MCE trajectories. A mixed-effect model was employed to examine the association between long-term care utilization and MCE in each trajectory., Results: Participants were stratified into four groups based on MCE trajectories over the 12 months preceding death as follows: rising (n = 159, 39.3%), persistently high (n = 143, 35.3%), minimal (n = 56, 13.8%), and descending (n = 47, 11.6%) groups. Home-based long-term care utilization was associated with increased MCE in the descending trajectory (coefficient, 1.48; 95% confidence interval [CI], 1.35-1.62). Facility-based long-term care utilization was associated with reduced MCE in the rising trajectory (coefficient, 0.59; 95% CI, 0.50-0.69). Both home-based (coefficient, 0.92; 95% CI, 0.85-0.99) and facility-based (coefficient; 0.53; 95% CI, 0.41-0.63) long-term care utilization were associated with reduced MCE in the persistently high trajectory., Conclusions: These findings may facilitate the integration of medical and long-term care models at the end of life in frail older adults., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Yoshiyuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Undernutrition and underweight are osteoporosis risk factors. Therefore, improving the health of underweight young women in Japan is an important medical issue. However, few studies have evaluated the association between being preconception underweight and postnatal osteoporotic fractures in young women., Methods: This retrospective cohort study used a Japanese nationwide claims database (JMDC Inc.) to evaluate the effect of preconception underweight on the incidence of osteoporotic fracture within two years after delivery. Data from 16,684 mothers who delivered their first singleton babies between January 2006 and December 2020 were analysed. The combination of disease codes of fractures at sites associated with osteoporosis and medical procedures for fractures was defined as the incidence of osteoporotic fractures, whereas the body mass index (BMI) recorded 12-36 months before delivery was used as the exposure. We estimated the incidence of osteoporotic fractures by BMI category using a Kaplan-Meier curve and examined the fracture risk using Cox hazard regression analyses., Results: Fifty-one women (0.31%) were affected by osteoporotic fractures within two years of delivery. More than 80% of these were rib fractures, and approximately 65% of fractures occurred after the first year postpartum. Preconception underweight (BMI < 18.5 kg/m 2 ) was significantly associated with the incidence of postpartum osteoporotic fractures. There was no significant association between low BMI and postnatal fractures, as analysed via multiple categorical logistic regression analysis., Conclusion: Appropriate control of preconception weight might be critical to improving the postpartum quality of life, subsequent bone health, and neonatal care environment., (© 2024. The Author(s).)

Background: The present study aimed to investigate prescription patterns for patients aged over 17 years with headaches in the REZULT database., Methods: We conducted a cross-sectional study (Study 1) of the proportion of over-prescription of acute medications (≥30 tablets/90 days for triptans, combination non-steroidal anti-inflammatory drugs (NSAIDs) and multiple types; ≥45 tablets/90 days for single NSAIDs) among patients with headache diagnosed in 2020. We longitudinally studied (Study 2) patients for >2 years from initial headache diagnosis (July 2010 to April 2022). The number of prescribed tablets was counted every 90 days., Results: In Study 1, headache was diagnosed in 200,055 of 3,638,125 (5.5%) patients: 13,651/200,055 (6.8%) received acute medication. Single NSAIDs were prescribed to 12,297/13,651 (90.1%) patients and triptans to 1710/13,651 (12.5%). Over-prescription was found in 2262/13,651 (16.6%) patients and 1200/13,651 (8.8%) patients received prophylactic medication. In Study 2, 408,183/6,840,618 (6.0%) patients were first diagnosed with headaches, which persisted for ≥2 years. Over time, the proportion of patients over-prescribed acute medications increased. Over 2 years, 37,617/408,183 (9.2%) patients were over-prescribed acute medications and 29,313/408,183 (7.2%) patients were prescribed prophylaxis at least once., Conclusions: According to real-world data, prophylaxis remains poorly prescribed, and both acute and prophylactic treatment rates for headaches have increased over time., Competing Interests: Declaration of conflicting interestsMasahito Katsuki received personal consultancy fees from Amgen Astellas BioPharma K.K., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K. and Otsuka Pharmaceutical Co., Ltd. during the conduct of the study.Yasuhiko Matsumori received personal consultancy fees from Amgen Astellas BioPharma K.K., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K. and Otsuka Pharmaceutical Co., Ltd. during the conduct of the study.Taisuke Ichihara and Yuya Yamada are employees of Japan System Techniques Co. Ltd.Keiichi Kaneko and Yasushi Kobayashi are employees in Bio-Medicines, Japan Drug Development & Medical Affairs at Eli Lilly Japan K.K. and own minor shares in Eli Lilly and Company.The other authors report no conflicts of interest concerning the materials or methods used in this study or the findings presented in this paper. This article and contents of this study were not published nor presented previously.

Background: Poor oral hygiene, generally manifesting as dental caries, gingivitis, or periodontitis, is a common chronic condition among both children and adults worldwide and has been reportedly associated with hypertension and arterial stiffness mainly in adult patients. However, these associations have not been well-studied in children and adults in the general population. Therefore, we conducted this cross-sectional study to clarify the associations between oral hygiene indices and high blood pressure (BP)/hypertension and arterial stiffness as assessed by the cardio-ankle vascular index (CAVI) in children along with their mothers. The association between maternal oral hygiene and high BP in children was also examined based on the hypothesis that maternal awareness of oral hygiene is related to their children's oral hygiene., Methods: This study was conducted as an Adjunct Study of the Aichi Regional Sub-Cohort of the Japan Environment and Children's Study. Participating children (n = 220, 85-104 months old) and their mothers (n = 217, 29-52 years old) underwent dental/intra-oral examination and BP and CAVI assessment. High BP in children and hypertension in mothers were diagnosed according to corresponding American guidelines. Logistic regression analysis or analysis of covariance was used to examine the associations of poor oral hygiene indices with BP and CAVI., Results: Maternal dental caries ≥1 was associated with their hypertension (adjusted odds ratio [aOR]: 2.72, 95% confidence interval (CI): 1.12-6.61). Maternal dental plaque ≥1/3 was associated with maternal hypertension and children's high BP (aOR, 95% CI: 4.71, 1.33-16.73 and 5.67, 1.22-25.04, respectively). Maximum pocket depth ≥4 mm was associated with children's high BP (aOR: 6.85, 95% CI: 1.24-38.01). No associations were observed between oral hygiene indices and CAVI in children; however, there was a significant association between dental plaque and CAVI in mothers (F = 5.62, p < 0.01)., Conclusions: The small sample size, especially the case number, made it necessary to refrain from drawing unambiguous conclusion. The hypothesis that warrants further investigation based on the present study results is that poor oral hygiene is associated with high BP in children and hypertension and arterial stiffness in mothers, and maternal oral hygiene is associated with high BP in children.

Objectives: The aim of this study was to compare the demographic characteristics of school-aged children with nocturnal enuresis and factors influencing hospital visits between two regions in Japan., Methods: A cross-sectional survey was conducted in Hirakata City, Osaka Prefecture, and Urayasu City, Chiba Prefecture. An anonymous online questionnaire was administered to all public elementary and junior high school students (aged 6-16 years) or their guardians. Questions included age, gender, perinatal history, frequency of nocturnal enuresis, frequency of bowel movements, comorbidities, and hospital visits for nocturnal enuresis., Results: The survey response rates were 15.4% in Hirakata City and 37.0% in Urayasu City. In total, 426 children with nocturnal enuresis in Hirakata City and 270 in Urayasu City were included in the final analysis. In both cities, the boy-girl ratio was approximately 2:1, and the prevalence of nocturnal enuresis gradually decreased with age. Multivariate analysis revealed that children aged ≥11 years had a significantly higher proportion of hospital visits (OR, 2.61; 95% CI: 1.49-4.56; p = 0.001; OR, 2.72; 95% CI: 1.12-6.64; p = 0.027, respectively). However, the frequency of nocturnal enuresis did not affect hospital visits., Conclusions: The findings of this study suggest that parents with school-aged children have low awareness that nocturnal enuresis is a health problem and therefore subject to medical consultation. Although the proportion of hospital visits increases for children aged ≥11 years, children and families suffering from nocturnal enuresis should be encouraged to see a doctor instead of adopting a "wait and see attitude," even at a young age., (© 2023 The Japanese Urological Association.)

Background: There is limited evidence regarding the relationship between Diabetes mellitus (DM) in middle age and mild cognitive impairment after a follow-up. Therefore, we investigated the relationship between fasting blood glucose (FBG) levels in middle age and cognitive function assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in later life, following over 15 years of follow-up in the Aichi Workers' Cohort Study in Japan., Methods: Participants were 253 former local government employees aged 60-79 years in 2018 who participated in a baseline survey conducted in 2002. Using baseline FBG levels and self-reported history, participants were classified into the normal, impaired fasting glucose (IFG) and, and DM groups. Total MoCA-J score ranges from 0 to 30, and cognitive impairment was defined as MoCA-J score ≤25 in this study. A general linear model was used to estimate the mean MoCA-J scores in the FBG groups, adjusted for age, sex, educational year, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, total cholesterol, and estimated glomerular filtration rate., Results: The mean MoCA-J score in the total population was 25.0, and the prevalence of MoCA-J score ≤25 was 49.0%. Multivariable-adjusted total MoCA-J scores were 25.2, 24.8, and 23.4 in the normal, IFG, and DM groups, respectively. The odds ratio of MoCA-J score ≤25 in the DM group was 3.29., Conclusion: FBG level in middle age was negatively associated with total MoCA-J scores assessed later in life, independent of confounding variables.

To determine the impact of the coverage of risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) as well as genetic testing for BRCA pathogenic variants by the national insurance system in Japan. We compared the clinical background of women who underwent RRSO at our institution before and after its coverage by the national insurance system. Those who underwent RRSO between January 2017 and December 2019 and between April 2020 and March 2022 were classified as Period. A and B, respectively. Overall, 134 women underwent RRSO during the study period. In Period A and B, 45 and 89 women underwent RRSO for the study period was 36 and 24 months, respectively. Compared with Period A, the number of women who underwent RRSO per month increased by threefold in Period B (p < 0.01). In addition, the number of women who underwent surgery for breast cancer along with RRSO increased in Period B (p < 0.01). Although the number of women who underwent concurrent RRM with RRSO in Period B increased, the difference was not statistically significant. Compared with Period A, the number of women diagnosed with BRCA pathogenic variant increased by 3.9-fold, and the proportion of women who underwent concurrent hysterectomy at the time of RRSO decreased from 66 to 7.9% in Period B (p < 0.01). Owing to the introduction of the national insurance system, the number of women who underwent RRSO and concurrent surgery for breast cancer at the time of RRSO increased in Japan., (© 2023. The Author(s).)

Insulin like growth factor-1 (IGF-1) plays important roles in metabolic functions, especially in adulthood. Additionally, obese subjects are reportedly predisposed to having low absolute IGF-1 levels. However, the prevalence and clinical characteristics of obese subjects with low IGF-1 levels are unknown. We examined 64 obese subjects with a body mass index (BMI) ≥ 35 kg/m 2 , with no history of endocrinological disorders, receiving inpatient care. IGF-1 levels were interpreted based on the IGF-1 standard deviation score (SDS) clinically used and standardized by age and sex (low IGF-1 group; ≤ - 2.0 SDS and standard IGF-1 group; - 2.0 < and <  + 2.0 SDS). Notably, 26.6% of the subjects had low IGF-1. Body fat mass and percentage, but not BMI, were significantly higher in the low than in the standard IGF-1 group. Furthermore, natural log-transformed high-sensitivity C-reactive protein, and the frequencies of dyslipidemia and hyperuricemia were higher in the low IGF-1 group. Moreover, among the subjects without diabetes, fasting glucose levels were significantly higher in the low IGF-1 group. Stepwise variable selection procedure revealed body fat percentage to be a parameter most strongly associated with low IGF-1. Thus, low IGF-1 levels may be an important marker of adiposity-associated metabolic disorders in obese patients., (© 2022. The Author(s).)

Various conjugative plasmids were obtained by exogenous plasmid capture, biparental mating, and/or triparental mating methods from different environmental samples in Japan. Based on phylogenetic analyses of their whole-nucleotide sequences, new IncP/P-1 plasmids that could be classified into novel subgroups were obtained. Mini-replicons of the plasmids were constructed, and each of them was incompatible with at least one of the IncP/P-1 plasmids, although they showed diverse iteron sequences in their oriV regions. There were two large clades of IncP/P-1 plasmids, clade I and II. Plasmids in clade I and II included antibiotic resistance genes. Notably, nucleotide compositions of newly found plasmids exhibited different tendencies compared with those of the previously well-studied IncP/P-1 plasmids. Indeed, the host range of plasmids of clade II was different from that of clade I. Although few PromA plasmids have been reported, the number of plasmids belonging to PromAβ, and -γ subgroups detected in this study was close to that of IncP/P-1 plasmids. The host ranges of PromAγ and PromAδ plasmids were broad and transferred to different and distinct classes of Proteobacteria . Interestingly, PromA plasmids and many IncP/P-1 plasmids do not carry any accessory genes. These findings indicate the presence of "hitherto-unnoticed" conjugative plasmids, including IncP/P-1 or PromA derivative ones in nature. These plasmids would have important roles in the exchange of various genes, including antibiotic resistance genes, among different bacteria in nature. IMPORTANCE Plasmids are known to spread among different bacteria. However, which plasmids spread among environmental samples and in which environments they are present is still poorly understood. This study showed that unidentified conjugative plasmids were present in various environments. Different novel IncP/P-1 plasmids were found, whose host ranges were different from those of known plasmids, showing wide diversity of IncP/P-1 plasmids. PromA plasmids, exhibiting a broad host range, were diversified into several subgroups and widely distributed in varied environments. These findings are important for understanding how bacteria naturally exchange their genes, including antibiotic resistance genes, a growing threat to human health worldwide.

There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants., Study Design: The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset., Results: A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05)., Conclusion: High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kaneko, Ito, Ebara, Kato, Matsuki, Tamada, Sato, Saitoh, Sugiura-Ogasawara, Yatsuya, Kamijima and The Japan Environment Children’s Study Group.)

Recently, along with increasing use of immune checkpoint inhibitors such as nivolumab, the incidence of immune-related adverse events, including type 1 diabetes mellitus, has become a serious problem. We report a patient who had immune checkpoint inhibitor‒associated type 1 diabetes mellitus that developed after a second mRNA-based SARS-CoV-2 vaccination.

In this real-world, retrospective cohort study of 9753 patients in Japan prescribed dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), we investigated DAPT duration and determined factors associated with early DAPT discontinuation and with event rates in patients who discontinued DAPT. The study period was April 1, 2012-March 31, 2018; endpoints comprised composite efficacy [death, myocardial infarction (MI), and stroke] and bleeding (intracranial, gastrointestinal, and requiring transfusion) endpoints. Overall, 68.8% of patients were continuing DAPT at 3 months post-PCI. Patients without major efficacy or safety events within 3 months after index PCI were included in a landmark analysis set (LAS; n = 7056), and categorized as DAPT ≥ 3 months (continuation) versus < 3 months (discontinuation). In the two LAS analysis groups, there was no difference in the composite bleeding endpoint (P = 0.067), although the incidence of the composite efficacy endpoint was higher in the discontinuation group (P < 0.001). In multivariate regression analysis, age ≥ 75 years, minor bleeding after PCI, history of cerebral infarction, history of cerebral or gastrointestinal bleeding, atrial fibrillation, dialysis, and anticoagulant use after PCI were associated with early DAPT discontinuation. Acute coronary syndrome, history of MI, kidney disorder, and anticoagulant use after PCI were associated with the composite efficacy endpoint in the discontinuation group. In conclusion, early DAPT discontinuation is more likely in patients at high bleeding risk, but may influence the occurrence of ischemic events in these patients. Determination of DAPT duration should take into account potential ischemic risk, even in patients at high bleeding risk., (© 2022. The Author(s).)

Background: Longitudinal adverse effects of neglect-related behaviors during postpartum, especially repeated maternal non-responsiveness to the crying baby on their neuropsychological developmental trajectory, have not been fully clarified., Objective: This study aimed to examine the association between postpartum maternal neglect-related behaviors and infant neuropsychological outcomes using the Japan Environment and Children's Study (JECS)., Participants and Setting: JECS data on 100,286 mother-child pairs were analyzed. Explanatory variables were "frequency of leaving the baby alone at home" (i.e., leaving the baby alone at home) and "frequency of ignoring the baby when he or she cries" (i.e., ignoring the crying baby) at one month postpartum. The outcomes were measured using the Japanese version of the Ages & Stages Questionnaires-Third Edition (J-ASQ-3)., Methods: After multiple imputations, logistic regression analysis was performed to evaluate the association between neglect-related behaviors and the J-ASQ-3 domains at each age., Results: The "sometimes or more" group of "ignoring the crying baby" from six months to three years reported relatively consistent significant associations with developmental delay in communication (maximum adjusted odds ratio [aOR]: 1.456, 95% confidence interval [CI]: 1.261-1.682), gross motor (maximum aOR: 1.279, 95% CI: 1.159-1.411), fine motor (maximum aOR: 1.274, 95% CI: 1.113-1.457), problem-solving (maximum aOR: 1.178, 95% CI: 1.104-1.256), and personal-social domains (maximum aOR: 1.326, 95% CI: 1.255-1.402). The adverse effects of "leaving the baby alone at home" disappeared in many domains by the age of one., Conclusions: Repeated maternal non-responsiveness to baby's crying during postpartum may suppress multiple neuropsychological development during early childhood., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Interruptions in undergraduate clinical clerkship during the COVID-19 pandemic have reduced the confidence and preparedness of residents beginning their postgraduate training. We explore the thoughts of new residents about this transition and reflect on the support needed., Methods: An exploratory qualitative case study was conducted with 51 residents. All had experienced interruptions in clinical training due to the pandemic and had just started their postgraduate training. Qualitative data were collected through 6 focus groups and 12 individual follow-up interviews. A thematic analysis was undertaken, and the data were categorised using a Strengths, Weaknesses, Opportunities, and Threats (SWOT) framework., Results: Graduates beginning their residency were aware of their professionalism and independence during the transition. They also faced the predicament of needing close supervision while their supervisors managed pandemic conditions. Residents emphasised the importance of developing relationships with colleagues and supervisors during the transition to residency and wanted direct observation and detailed feedback from their supervisors during procedures., Conclusions: The experiences of residents were not uniformly negative. In fact, some had developed a positive mindset when entering the clinical field. Medical faculty members reflecting on interactions with new residents and planning future clinical internships could benefit from placing a high value on building relationships among residents, who may expect direct observation and detailed feedback from their supervisors., Competing Interests: The authors have declared that no competing interests exist.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language., (© 2021 The Authors. Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)

Background: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year., Methods: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH 2 -FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer., Results: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH 2 -FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH 2 -FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60)., Conclusions: This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.

Context: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive., Objective: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA., Methods: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts., Results: The mean gestational age at blood sampling was 22.7 ± 4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20)., Conclusion: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65-84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94-2.48], Low; 1.86 [1.02-3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98-2.02], Low; 1.49 [1.04-2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64-11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk., (© 2021. The Author(s).)

The red alga Laurencia nipponica comprises various chemical races distributed relative to the ocean current in Japanese coastal areas. We investigated the chemical compositions and chemical races of L. nipponica distributed from the Kunashiri and Etorofu Islands, the confluence of the Soya warm current and Oya-shio cold current. Two new halogenated secondary metabolites, deacetylneonipponallene (1) and neopacifenol (2), along with four known compounds, deoxyprepacifenol (3), pacifenol (4), halo-chamigrene diether (5), and isolaurallene (6) were isolated from L. nipponica collected at Chikappunai, Kunashiri Island, while Zaimokuiwa (Kunashiri Island) and Sana (Etorofu Island) populations contained 3, 7-hydroxylaurene (7), 2,10-dibromo-3-chloro-9-hydroxy-α-chamigrene (8), and (3Z)-laurefucin (9). The structures of 1 and 2 were established using spectroscopic methods. The chemical races of L. nipponica distributed in this area were divided into 6- and 9-producing races. Interestingly, both races contained 4 as an additional race-index, as well as its derivatives, 2 and 5. To the best of our knowledge, this is the first example of a race comprising a mixture of two race-index compounds, suggesting that the convergence of two currents causes the production of new and diverse chemical races in this species., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Objectives: To evaluate whether the efficacy of desmopressin differs between patients with and without nocturnal polyuria., Methods: A total of 65 treatment-naïve children with monosymptomatic nocturnal enuresis were enrolled (45 boys; median age 8.9 years). Patients received desmopressin as their first-line treatment. Four different standards were used (Akashi and Hoashi >0.9 mL/kg/sleeping hour; Hamano >[age + 2] × 25 × 130% mL; the International Children's Continence Society >[age + 1] × 30 × 130% mL; and Rittig >[age + 9] × 20 mL) to assess nocturnal polyuria. The effectiveness of desmopressin was compared between patients with and without nocturnal polyuria according to each standard. A response was defined as a reduction in wet nights of >50%., Results: The desmopressin treatment efficacy rate was 54% for polyuria and 67% for non-polyuria patients (P = 0.20), 45% for polyuria and 68% for non-polyuria patients (P = 0.08), 54% for polyuria and 59% for non-polyuria patients (P = 0.80), and 52% for polyuria and 61% for non-polyuria patients (P = 0.61), for the Akashi and Hoashi's, Hamano's, International Children's Continence Society and Rittig's standards, respectively., Conclusions: No difference was observed in the short-term clinical efficacy of desmopressin regardless of the presence of nocturnal polyuria. Thus, this might be a feasible treatment option for patients with nocturnal enuresis without nocturnal polyuria., (© 2021 The Japanese Urological Association.)

On 11 March 2011, a catastrophic earthquake and subsequent tsunami hit the Pacific coast of northern Japan, devastating many of the towns, villages and coastal ecosystems located along the shoreline. To assess the impacts of the disaster, we investigated temporal dynamics of fish and epibenthic megafaunal community structure in relation to changes in a range of physical, biological and anthropogenic variables between 2007 and 2018 in Onagawa Bay. Commercially important fish such as greenlings, Japanese anchovy, flatfishes, rockfishes were consistently abundant in both larval and adult fish assemblages. While abundance, species richness, and Shannon index H' for adult fish and epibenthic megafaunal assemblages increased significantly soon after the disaster to peak values towards the end of the study period, the same metrics did not change accordingly for larval fish assemblages. Temporal dynamics of larval fish community clearly demonstrated significant seasonal variation along with changes in large-scale environmental conditions such as temperature and nutrients. However, anthropogenic components such as decline in human population, reduction in fishing pressure and the recovery of aquaculture operations significantly explained the observed post-disaster change in adult fish and epibenthic megafaunal communities. The pelagic and benthic components of Onagawa Bay appeared to have responded to the 2011 disaster very differently, and this study suggests the post-disaster recovery and dynamics of the coastal ecosystems may be regulated by how human societies respond to the impacts of a tsunami catastrophe through their influences on benthic habitat of ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

It is difficult to investigate clinical features in a single-center study because atypical periprosthetic femoral fracture (APFF) is rare. This study aims to perform a nationwide survey of APFF to investigate the characteristics of this fracture and compare the clinical outcome with that of typical periprosthetic femoral fracture (typical PFF). A nationwide survey was performed asking for cooperation from 183 councilors of the Japanese Society for Fracture Repair. The subjects were patients with APFF injured between 2008 and 2017. The control group was comprised of patients with typical PFF of our facility injured in the same period. A total of 43 patients met the APFF definition. The control group was comprised of 75 patients with typical PFF. The rate of bisphosphonate use was significantly higher in the APFFs group than in the typical PFF group (62.8% and 32%, p < 0.02). The rate of cemented stem was significantly higher in the APFFs group than in the typical PFF group (30.2% and 6.7%, p < 0.001). In the patients with arthroplasty for hip fracture, multivariable logistic regression analyses showed that APFF was an independent risk factor of complications following the initial management (Odds ratio 11.1, 95% confidence interval 1.05-117.2, p = 0.045). However, no significant association between PFF and APFF was observed in the patients with arthroplasty for other hip diseases. The risk of complications was higher in the APFF group than in the typical PFF group in the patients with arthroplasty for fracture. When AFPP after arthroplasty for the fracture is suspected, it may be necessary to add not only internal fixation with a normal plate but also some additional treatment., (© 2021. The Author(s).)

Perioperative oral management is widely recognized in the healthcare system of Japan. Conventionally, the surgeon refers patients with oral problems to a dental or oral surgery clinic in the hospital. However, frequent in-house referrals were found to increase the number of incoming patients resulting in unsustainable situations due to an insufficient workforce. In 2011, the Center for Perioperative Medicine was established at our hospital to function as a management gateway for patients scheduled to undergo surgery under general anesthesia. The "oral triage" system, wherein a dental hygienist conducts an oral screening to select patients who need preoperative oral hygiene and functional management, was established in 2012. A total of 37,557 patients who underwent surgery at our hospital from April 2010 to March 2019 (two years before and seven years after introducing the system) were evaluated in this study. The sustainability and effectiveness of introducing the system were examined in 7715 cancer surgery patients. An oral management intervention rate of 20% and a significant decrease in the incidence of postoperative pneumonia (aOR = 0.50, p = 0.03) indicated that this system could be useful as a sustainable and developmental oral management strategy to manage surgical patients with minimal human resources.

A total of 55 samples of intestinal contents from 28 raccoon dogs (Nyctereutes procyonoides) and 27 badgers (Males anakuma) in Miyazaki prefecture, Japan, were examined for the presence of Campylobacter species. C. jejuni and C. upsaliensis were isolated from 3.6% (n = 1) and 75% (n = 21) of raccoon dogs, respectively. In contrast, no Campylobacter spp. was isolated from the badgers examined. The C. upsaliensis isolates were subjected to antimicrobial susceptibility testing against 8 antimicrobial agents. This revealed that most of the isolates from raccoon dogs were susceptible to the antimicrobial agents examined, whereas strains isolated from healthy dogs in Miyazaki prefecture, showed high rates of resistance. Virulence genes (flaA, cadF, ciaB, cdtA, cdtB, and cdtC) were present in the C. jejuni isolate from a raccoon dog, with the exception of flaB. By contrast, all these virulence genes examined were present in all C. upsaliensis strains isolated from raccoon dogs and dogs. The genetic diversity of those isolates based on the nucleotide sequences of 7 housekeeping genes (adk, aspA, atpA, glnA, glyA, pgi, tkt) was compared with that of C. upsaliensis strains isolated from dogs and strains selected randomly from humans and dogs deposited in the Campylobacter MLST database. The major cluster of raccoon dog strains was separated from both human and dog strains by phylogenetic tree analysis. These results suggest that raccoon dogs are a reservoir of C. upsaliensis and that isolates may represent a population different from that in humans and dogs. To our knowledge, this is the first study to have demonstrated a high prevalence of C. upsaliensis in raccoon dogs., (© 2021. EcoHealth Alliance.)

Objective: To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey., Methods: Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center had any patients with ADS, and the MOG-IgG serostatus of the patients. In a follow-up survey, we requested more precise information on patients with ADS., Results: Initial survey: 263 replies providing information on 175 patients were received. MOG-IgG were examined in 78 patients and 54 of those (69%) were positive for MOG-IgG. Follow-up survey: The characteristic involvement was optic neuritis, with visual disturbance and optic pain as characteristic symptoms. The relapse rate was 44% in patients positive for MOG-IgG, which was higher than that in seronegative patients (38%). For acute phase treatments, corticosteroid (CS), plasma exchange, and intravenous immunoglobulin (IVIG) were useful. To prevent relapse, CS, intermittent IVIG, immunosuppressants, and monoclonal antibodies were useful, but the efficacies of disease modifying drugs were uncertain. Sequelae such as visual disturbance, cognitive impairment, motor dysfunction, and epilepsy were observed in 11% of patients with MOG-IgG., Conclusions: MOG antibody-associated diseases were found to be common among pediatric ADS patients. Since a variety of sequelae were observed in these patients, it is important to identify the appropriate treatment to ensure the best outcome. The presence of the MOG autoantibody should be taken into consideration as part of the diagnostic criteria for pediatric ADS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Examining the predictors of summative assessment performance is important for improving educational programs and structuring appropriate learning environments for trainees. However, predictors of certification examination performance in pediatric postgraduate education have not been comprehensively investigated in Japan., Methods: The Pediatric Board Examination database in Japan, which includes 1578 postgraduate trainees from 2015 to 2016, was analyzed. The examinations included multiple-choice questions (MCQs), case summary reports, and an interview, and the predictors for each of these components were investigated by multiple regression analysis., Results: The number of examination attempts and the training duration were significant negative predictors of the scores for the MCQ, case summary, and interview. Employment at a community hospital or private university hospital were negative predictors of the MCQ and case summary score, respectively. Female sex and the number of academic presentations positively predicted the case summary and interview scores. The number of research publications was a positive predictor of the MCQ score, and employment at a community hospital was a positive predictor of the case summary score., Conclusion: This study found that delayed and repeated examination taking were negative predictors, while the scholarly activity of trainees was a positive predictor, of pediatric board certification examination performance.

Introduction: Mycoplasma pneumoniae contributes to numerous pneumonia cases among children and young adults. Therefore, this study aimed to investigate the prevalence of M. pneumoniae infections among Japanese children, occurring since 2008., Methods: Nasopharyngeal swab specimens were obtained from all cases, following which real-time PCR was performed to identify M. pneumoniae. Further, the p1 genotypes of isolates were determined using the PCR restriction fragment length polymorphism typing method., Results: The annual rate of macrolide-resistant M. pneumoniae (MRMP) infections peaked at 81.8% in 2012 and decreased annually until 2015. Although the infection rate increased to 65.3% in 2016, it decreased again to 14.3% in 2018. Although >90% of isolates harbored the type 1 genotype until 2012, this rate decreased, and approximately 80% harbored p1 genotypes other than type 1 in 2018. Furthermore, the occurrence rate of MRMP among the type 1 isolates was very high (82.4%), whereas that among p1 genotypes other than type 1 was very low (6.5%)., Conclusions: MRMP occurrence potentially decreased owing to changes in not only antibiotic usage but also in the distribution of p1 genotype among isolates., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A novel mesophilic sulfate-reducing bacterium, strain HN2 T , was isolated from groundwater sampled from the subsurface siliceous mudstone of the Wakkanai Formation located in Horonobe, Hokkaido, Japan. The bacterium was Gram-negative and vibrio-shaped, and its motility was conferred by a single polar flagellum. Cells had desulfoviridin. Catalase and oxidase activities were not detected. It grew in the temperature range of 25-40 °C (optimum, 35 °C) and pH range of 6.3-8.1 (optimum, pH 7.2-7.6). It used sulfate, thiosulfate, dimethyl sulfoxide, anthraquinone-2,6-disulfonate, Fe 3+ , and manganese oxide, but not elemental sulfur, nitrite, nitrate, or fumarate as electron acceptors. The strain showed weak growth with sulfite as the electron acceptor. Fermentative growth with pyruvate, lactate and cysteine was observed in the absence of sulfate, but not with malate or fumarate. NaCl was not required, but the strain tolerated up to 40 g l -1 . Strain HN2 T did not require vitamins. The major cellular fatty acids were iso-C 15 : 0 (23.8 %), C 18 : 1  ω 9 t (18.4 %), C 18 : 0 (15.0 %), C 16 : 0 (14.5 %), and anteiso-C 17 :0 (10.1 %). The major respiratory quinone was menaquinone MK-6(H 2 ). The G+C content of the genomic DNA was 56.7 mol%. Based on 16S rRNA gene sequence analysis, the closest phylogenetic relative of strain HN2 T is Desulfovibrio psychrotolerans JS1 T (97.0 %). Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values of the strains HN2 T and D. psychrotolerans JS1 T were 22.2 and 79.8 %, respectively. Based on the phenotypic and molecular genetic evidence, we propose a novel species, D. subterraneus sp. nov. with the type strain HN2 T (=DSM 101010 T =NBRC 112213 T ).

To compare early vascular healing following cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation between groups with or without aggressive stent expansion in patients treated by CoCr-EES for stable coronary artery disease (CAD). Seventy-one stable CAD lesions underwent CoCr-EES implantation and analysis of serial optical coherence tomography (OCT) images obtained post-procedure and at early-term (1- or 3-month) follow-up. The endpoints of this study were neointimal thickness at the time of 1- or 3-month OCT and presence and healing of stent edge dissection. Aggressive stent expansion was defined as a lesion complying with ILUMIEN III sizing protocol; that is, external elastic lamina (EEL) diameter minus maximum balloon diameter ≤ 0.25 mm.  Comparing groups with and without aggressive stent expansion, median neointimal thickness at 1 and 3 months after CoCr-EES implantation was similar (1 month: 0.031 mm vs. 0.041 mm, respectively, p = 0.27; 3 months: 0.036 mm vs. 0.040 mm, respectively, p = 0.84). Regarding stent edge findings, the presence of any stent edge dissection immediately after percutaneous coronary intervention was also similar between the groups (25% vs. 15%, respectively; p = 0.30) and most stent edge dissections resolved completely within 3 months, regardless of location or dissection severity. After 1 year, no clinically driven target lesion revascularization or stent thrombosis was observed in either cohort. Even after aggressive stent expansion, early neointimal proliferation appeared modest with CoCr-EES implantation, and most stent edge dissections had resolved by 3 months. These findings may support the feasibility of EEL-based sizing by pre-stenting OCT.

Background: This study aimed to validate and determine the minimal clinically important difference (MCID) in the Japanese version of the International Knee Documentation Committee Subjective Knee Form (Japanese IKDC-SKF) for patients with anterior cruciate ligament (ACL) injuries., Methods: This prospective study was performed using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guideline to assess the measurement properties of reliability, responsiveness, validity, and interpretability of the Japanese IKDC-SKF., Results: A total of 152 patients were enrolled in the study. The Japanese IKDC-SKF had excellent internal consistency [Cronbach's alpha (95% confidence interval, CI) was 0.90 (0.88-0.92), and the test-retest reliability [intraclass correlation coefficient, ICC 2,1 (95% CI)] was 0.97 (0.94-0.98). The content validity (r), which was interpretable between the Japanese IKDC-SKF and the Japanese Anterior Cruciate Ligament questionnaire 25 was -0.87 (P < 0.001). The construct validity for the IKDC-SKF was 86% (six of seven hypotheses were consistent with the results), also indicating high validity. Responsiveness of the Japanese IKDC-SKF was confirmed, with an acceptable area under the curve of 0.81 and a large effect size (Cohen's d of 0.8). There were no floor or ceiling effects. The MCID for the Japanese IKDC-SKF for ACL injury was 10.7., Conclusions: Our results indicate that the Japanese version of the IKDC-SKF is a reliable, valid, and responsive measurement instrument with which to evaluate the physical function of patients with ACL injuries., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

This study aimed to determine the seasonal impact on the clinical onset of inflammatory neurological diseases of the central nervous system by analyzing the onset month with information on clinical manifestations in Japanese patients. As a result, patients with anti-aquaporin-4 antibodies (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD) showed spring-summer predominance of the clinical onset. Conversely, patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease showed autumn-winter predominance of the clinical onset. Both seasonal variations were irrespective of the clinical manifestation. Environmental factors with seasonal variation influence the development of neurological conditions related to AQP4-IgG and MOG-IgG., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Inhaler therapy is the mainstay of chronic obstructive pulmonary disease (COPD) management. Poor adherence causes disease exacerbation and affects patient mortality. Although the Adherence Starts with Knowledge-20 (ASK-20) questionnaire is a reliable tool for assessing medication adherence, the relationship between the ASK-20 and clinical factors in patients with COPD remains unknown. We investigated the relationship between the ASK-20 and clinical factors, and assessed real-world inhaler therapy use., Patients and Methods: A multicenter, cross-sectional study of outpatients with COPD undergoing inhaler treatment who completed the ASK-20 questionnaire was performed. We investigated COPD-related health status using the COPD Assessment Test (CAT), psychological status using the Hospital Anxiety and Depression Scale (HADS-anxiety and HADS-depression), respiratory function, patient satisfaction levels, and real-world inhaler therapy use., Results: Of the total 319 patients, 87% were male with a median age of 74 years. Most patients had mild or moderate COPD, according to Global Initiative for Chronic Obstructive Lung Disease stage. The total ASK-20 scores correlated significantly with the CAT, HADS-anxiety, and HADS-depression scores (r = 0.27, 0.33, and 0.29, respectively, p < 0.01). Multivariable analysis showed that CAT and HADS-anxiety scores had an independent and significant impact on the ASK-20 scores [β, standardized regression coefficient: 0.18 (95% CI, 0.03-0.35; p = 0.02), and 0.29 (95% CI, 0.17-0.42; p < 0.01), respectively]; however, the ASK-20 scores were not correlated with age, sex, body mass index, cohabitation, modified Medical Research Council Dyspnea Scale score, pulmonary function, disease duration, number of COPD exacerbations per year, comorbidities, inhaler numbers, nor inhaler components., Conclusion: The ASK-20 scores in patients with COPD were significantly associated with CAT and HADS scores. In Japan, Respimat was prescribed to younger patients and patients with lower CAT scores. The ASK-20, a simple evaluation method, is useful for identifying clinical factors affecting adherence in patients with COPD., Competing Interests: Shintaro Suzuki reports a grant from KAKENHI (20K03161) and a sponsored research grant from MylanEPD (JAPAN), outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2020 Akimoto et al.)

Background: Limited data is available on the use of a polyester graft limb with a helical stent configuration deployed in the external iliac artery (EIA) during endovascular aneurysm repair (EVAR), so we prospectively analyzed the efficacy of the Zenith Spiral-Z limb deployed in the EIA., Methods and results: Patients undergoing EVAR using a Zenith stent-graft and Spiral-Z limb deployed in the EIA were prospectively registered in 24 Japanese institutions from June 2017 to November 2017. In total, 65 patients (74 limbs) (mean age: 77.1±8.0 years, 87.7% men, mean abdominal aortic aneurysm (AAA) diameter: 51.9±7.2 mm, mean iliac artery aneurysm (IAA) diameter: 38.3±10.0 mm) were registered and followed up. The most common reason for deployment in the EIA was a common IAA (43 limbs, 58.1%), and 8 limbs (10.8%) had a bare nitinol stent placed at the Spiral-Z limb. A total of 61 patients (70 limbs) completed a 24-month follow-up. There were 2 Spiral-Z limb stenoses and 1 occlusion, leading to a primary patency of 95.5% and a secondary patency of 100%, at 24 months. Buttock claudication occurred in 24.3% of the limbs treated at 1 month but decreased to 4.3% at 24 months., Conclusions: Our multicenter prospective study showed that Spiral-Z limb deployed in the EIA was associated with satisfactory results and seems to be a durable option, even in the era of iliac branch devices.

Background: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients., Methods and results: Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m 2 ), and cardiac index (CI; L/min/m 2 ). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group., Conclusions: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Aims/introduction: The Japanese government started a nationwide screening program for metabolic syndrome (MetS) to prevent cardiovascular diseases and diabetes in 2008. Although impaired fasting glucose (IFG) is a strong predictor for type 2 diabetes mellitus, the program does not follow up IFG in non-MetS individuals. This study aimed to examine the risk and the population attributable fraction (PAF) of MetS and IFG for incidence of type 2 diabetes mellitus., Materials and Methods: Japanese workers (3,417 men and 714 women) aged 40-64 years without a history of diabetes were prospectively followed. MetS was defined as either abdominal obesity plus two or more metabolic risk factors, or being overweight in the case of normal waist circumference plus three or more metabolic risk factors. IFG was defined as fasting blood glucose 100-125 mg/dL., Results: During a mean 6.3 years, 240 type 2 diabetes mellitus cases were identified. Compared with those without MetS and IFG, the multivariable-adjusted hazard ratios (95% confidence interval) of non-MetS individuals with IFG, MetS individuals without IFG and MetS individuals with IFG for type 2 diabetes mellitus were 4.9 (3.4-7.1), 2.4 (1.6-3.5) and 8.3 (5.9-11.5), respectively. The corresponding PAFs for type 2 diabetes mellitus incidence were 15.6, 9.1 and 29.7%, respectively., Conclusions: IFG represented a higher risk and PAF than MetS for type 2 diabetes mellitus incidence in middle-aged Japanese individuals. The coexistence of MetS and IFG showed the highest risk and PAF for type 2 diabetes mellitus incidence. The current Japanese MetS screening program should be reconsidered to follow up non-MetS individuals with IFG., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

We investigated two sediment cores to understand whether a tsunami in Onagawa Bay, Japan caused environmental changes. The value of δ 13 C ranged from -21.9‰ to -24.3‰ and of δ 15 N ranged from 5.1 to 5.9‰. We conclude that the source of the sediment in the present study area was mainly oceanic and not terrestrial. The chlorophyll concentration ranged from 1.8 to 4.0 μg/g ww, and did not vary greatly between surface and bottom layers. We inferred that all layers were deposited after the tsunami. The major phytoplankton taxa in sediments were diatoms from DNA sequencing. The presence of harmful dinoflagellates was minor. The concentrations of several heavy metals decreased slightly after the tsunami. We inferred that heavy metals in sediments were diluted by the tsunami disturbance. The land in Onagawa suffered serious damage, but disturbance of the seabed was much less evident., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72&#95;73delGA, in BMPR1A. The proband's elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified., (© The Author(s) 2020. Published by Oxford University Press.)