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Regeneration of articular cartilage remains a challenge for patients who have undergone cartilage injury, osteochondritis dissecans and osteoarthritis. Here, we describe a new recombinant silk fibroin with basic fibroblast growth factor (bFGF) binding peptide, which has a genetically introduced sequence PLLQATLGGGS, named P7. In this study, we cultured a human mesenchymal cell line derived from bone marrow, UE6E7-16, in wild-type fibroin sponge (FS) and recombinant silk fibroin sponge with P7 peptide (P7 FS). We compared cell proliferation, chondrogenic differentiation and cartilaginous tissue formation between the two types of sponge. After stimulation with bFGF at 3 ng/mL, P7 FS showed significantly higher cell growth (1.2-fold) and higher cellular DNA content (5.6-fold) than did wild-type FS. To promote chondrogenic differentiation, cells were cultured in the presence of TGF-β at 10 ng/mL for 28 days. Immunostaining of P7 FS showed SOX9-positive cells comparable to wild-type FS. Alcian-Blue staining of P7 FS also showed cartilaginous tissue formation equivalent to wild-type FS. A significant increase in cell proliferation in P7 FS implies future clinical application of this transgenic fibroin for regeneration of articular cartilage. To produce cartilaginous tissue efficiently, transgenic fibroin sponges and culture conditions must be improved. Such changes should include the selection of growth factors involved in chondrogenic differentiation and cartilage formation.

Objectives: Previous studies have shown possible choroid plexus (CP) dysfunction in Alzheimer's disease (AD) and highlighted CP enlargement on magnetic resonance imaging (MRI) as a predictive factor of AD. However, few studies have assessed the relationship between CP volume (CPV) and mild cognitive impairment (MCI). In this large elderly population study, we investigated the changes in CPV in patients with MCI using MRI above 65 years., Methods: This cross-sectional study included 2144 participants (median age, 69 years; 60.9% females) who underwent 3T MRI; they were grouped as 218 MCI participants and 1904 cognitively healthy controls. The total intracranial volume (ICV), total brain volume (TBV), CPV, hippocampal volume (HV), and lateral ventricle volume (LVV) were calculated., Results: CPV/ICV was a significant independent predictor of MCI (p < 0.01) after adjusting for potential confounders (age, sex, hypertension, hyperlipidemia, diabetes, and education level). The CPV/ICV ratio was also a significant independent predictor of MCI after adjusting for the TBV/ICV ratio (p = 0.022) or HV/ICV ratio (p = 0.017), in addition to potential confounders. The CPV was significantly correlated with the LVV (r = 0.97, p < 0.01)., Conclusion: We identified a relationship between CPV and MCI, which could not be explained by the degree of brain atrophy. Our results support CP dysfunction in MCI., Clinical Relevance Statement: Choroid plexus volume measurement may serve as a valuable imaging biomarker for diagnosing and monitoring mild cognitive impairment. The enlargement of the choroid plexus, independent of brain atrophy, suggests its potential role in mild cognitive impairment pathology., Key Points: • The study examines choroid plexus volume in relation to cognitive decline in elderly. • Enlarged choroid plexus volume independently indicates mild cognitive impairment presence. • Choroid plexus volume could be a specific biomarker for early mild cognitive impairment diagnosis., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Previously, we demonstrated that childhood maltreatment could worsen depressive symptoms through neuroticism. On the one hand, some studies report that sleep disturbances are related to childhood maltreatment and neuroticism and worsens depressive symptoms. But, to our knowledge, no reports to date have shown the interrelatedness between childhood maltreatment, neuroticism, and depressive symptoms, and sleep disturbance in the one model. We hypothesized that sleep disturbance enhances the influence of maltreatment victimization in childhood or neuroticism on adulthood depressive symptoms and the mediation influence of neuroticism between maltreatment victimization in childhood and adulthood depressive symptoms., Subjects and Methods: Total 584 Japanese volunteer adults recruited through convenience sampling from 4/2017 to 4/2018 were assessed regarding their characteristics of demographics, history of childhood maltreatment, sleep disturbance, neuroticism, and depressive symptoms with questionnaires self-administered. Survey data were analyzed using simple moderation models and a moderating mediation model., Results: The interaction of sleep disturbance with childhood maltreatment or neuroticism on depressive symptoms was significantly positive. Furthermore, the moderating effect of sleep disturbance on the indirect effect of childhood maltreatment to depressive symptoms through neuroticism was significantly positive., Limitations: Because this was a cross-sectional study, a causal relationship could not be confirmed., Conclusions: Our findings indicate that individuals with milder sleep disturbance experience fewer depressive symptoms attributable to neuroticism and childhood maltreatment. Additionally, people with less sleep disturbance have fewer depressive symptoms arising from neuroticism owing to childhood maltreatment. Therefore, improvement of sleep disturbance will buffer the aggravating effect of childhood maltreatment, neuroticism caused by various factors, and neuroticism resulting from childhood maltreatment on depressive symptoms., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Jiro Masuya has received personal compensation from Otsuka Pharmaceutical, Eli Lilly, Astellas, MSD, Janssen Pharmaceutical, Takeda Pharmaceutical, Shionogi Pharmaceutical, and Meiji Yasuda Mental Health Foundation, as well as grants from Pfizer, and Mitsubishi Tanabe Pharma. Yu Tamada received honoraria from Otsuka Pharmaceutical, Sumitomo Pharma, Eisai, MSD and Meiji Seika Pharma. Takeshi Inoue has received personal fees from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Ono Pharmaceutical; a grant from Astellas; and grants and personal fees from Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Shionogi, Tsumura, Novartis Pharma, Eisai, Daiichi Sankyo, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. All other authors declare that they have no actual or potential conflicts of interest associated with this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Masuya 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.)

Purpose: A growing body of evidence suggests that oral health is associated with a wide range of health outcomes; however, opinions tend to vary because of inconsistent findings. This study aimed to simultaneously examine the association between oral health status and multiple health and well-being indicators using outcome-wide epidemiology., Methods: Data were obtained from the Japan Gerontological Evaluation Study. Oral health status was categorized as: ≥20 teeth, 10-19 teeth with dental prosthesis, 0-9 teeth with prosthesis, 10-19 teeth without prosthesis, and 0-9 teeth without prosthesis. We examined the associations between oral health status in 2013 and 35 health and well-being outcomes in 2019, including physical/cognitive health, psychological distress, subjective health, social well-being, prosocial/altruistic behaviors, and health behaviors, using two databases (n=32,827 and 15,905)., Results: Compared to individuals with ≥20 teeth, those with <20 teeth had a 10-33% higher risk of mortality and a 6-14% higher risk of functional disability six years later. Additionally, individuals with fewer than 20 teeth tended to go out less frequently and eat fewer vegetables and fruits. Furthermore, individuals with 0-9 teeth without a prosthesis were more likely to have severe functional disability (risk ratio (RR):1.17, 95% confidence interval (CI):1.05-1.31), engage in fewer intellectual activities (standardized difference: 0.17, 95% CI: 0.10-0.24), and feel more hopeless (RR: 1.21, 95% CI: 1.04-1.41)., Conclusions: The prevention of tooth loss and prosthodontic treatment may be associated with reduced mortality and functional disability, as well as maintenance of intellectual ability, frequency of going out, and improvements in dietary lifestyle.

Purpose: Laughter is expected to have health-protective effects, but the potential link between tooth loss and laughter remains unclear. Therefore, this study aimed to examine the association between tooth loss and a low frequency of laughter among older adults in Japan, to elucidate whether this association could be mitigated by dental prostheses, and to evaluate the magnitude of the association mediated by poor oral function., Methods: We used cross-sectional data from 157,708 functionally independent participants aged ≥65 years (46.3% male) from the Japan Gerontological Evaluation Study. A modified Poisson regression model was applied to examine the association between the number of remaining teeth (≥20/10-19/0-9), dental prostheses use, and infrequent laughter (i.e., laughing never or almost never). Causal mediation analysis was performed to assess whether the association was mediated by difficulties in eating hard foods, choking, or dry mouth., Results: Among the participants, 9,129 reported infrequent laughter. Participants with ≤9 and 10-19 teeth who did not use dental prostheses had a 1.29 and 1.14 times higher likelihood of infrequent laughter than those with ≥20 teeth, respectively. Furthermore, difficulty eating hard foods, choking, and dry mouth mediated 22.8%, 0.4%, and 4.3% of the association between fewer remaining teeth and infrequent laughter, respectively. Meanwhile, we did not find evidence for the differences in infrequent laughter between participants with ≤19 teeth using dental prostheses and those with ≥20 teeth., Conclusions: Tooth loss among individuals without dental prostheses was associated with infrequent laughter, and this association was mediated by poor oral function.

Objective: This study aimed to determine whether the frequency of eating together is associated with the incidence of functional disability in older adults who live alone., Methods: This 6-year observational prospective cohort study utilised self-reported questionnaires. Data were drawn from the participants of the Japan Gerontological Evaluation Study project between 2016 and 2022. The participants were independent older adults aged ≥65 years living alone in Japan. The primary outcome was the incidence of functional disability during the follow-up period, with the self-reported frequency of eating together serving as the explanatory variable. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models after adjusting for confounders associated with incident functional disability., Results: Among the 7167 participants, the mean age at baseline was 75.3 ± 6.5 years and 69.2% were female. About, 12.8% of participants (n = 917) developed functional disabilities during the observation period. The incidence rates were 11.7% for 'every day', 11.3% for 'several times a week', 11.5% for 'several times a month', 12.7% for 'several times a year' and 19.0% for 'seldom'. The frequency of eating together 'seldom' was significantly associated with an increased incidence of functional disability (HR: 1.55, 95% CI: 1.10-2.18)., Conclusion: Among older adults living alone, infrequent eating together ('seldom') was identified as a risk factor for developing functional disability., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Rationale and Objectives: Although hyperintensity in the anterior portion of the callosal splenium on FLAIR (aCS-hyperintensity) is a common finding in elderly adults, no previous studies have examined the clinical significance. In this large elderly population study, we aimed to investigate the associations of aCS-hyperintensity with vascular risk factors, cognitive decline, and other MRI measurements., Materials and Methods: This cross-sectional study included 2110 participants (median age, 69 years; 61.1% females) who underwent 3 T MRI. The participants were grouped as 215 with mild cognitive impairment (MCI) and 1895 cognitively normal older adults (NOAs). Two neuroradiologists evaluated aCS-hyperintensity by using a four-point scale (none, mild, moderate, and severe). Periventricular hyperintensities (PVHs) were also rated on a four-point scale according to the Fazekas scale. The total intracranial volume (ICV), total brain volume, choroid plexus volume (CPV), and lateral ventricle volume (LVV) were calculated., Results: Logistic regression analysis showed diabetes was the main predictor of aCS-hyperintensity after adjusting for potential confounders (age, sex, hypertension, and hyperlipidemia) (p < 0.01), whereas PVH was associated with hypertension (p < 0.01). aCS-hyperintensity rated as "severe" was associated with a presence of MCI (p < 0.01). For the imaging factors, LVV was an independent predictor of aCS-hyperintensity when brain volume and PVH grade were added to the analysis (p < 0.01)., Conclusion: Cerebral small vessel disease due to diabetes is a major contributor to the development of aCS-hyperintensity. Cerebrospinal fluid clearance failure may also relate to aCS-hyperintensity, which may offer new insights into the pathologic processes underlying MCI., 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 © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Aim: Various factors are thought to be involved in the development of depression, but the mechanisms are not yet clear. Although several reports have demonstrated that parental attitude experienced in childhood, depressive rumination, and sleep disturbances each influence depressive symptoms, and the association between two of these four variables, to our knowledge, no reports to date have investigated the association among the four variables., Methods: A questionnaire survey was administered to 576 adults who agreed to participate in this study between April 2017 and April 2018. Questionnaires assessed parental attitudes experienced in childhood, depressive rumination, sleep disturbances, and depressive symptoms in adulthood. The associations among the four variables were tested by structural equation modeling., Results: Regarding the direct effects, the parental attitude of "care" had a negative influence on depressive rumination and depressive symptoms, whereas "overprotection" had a positive influence on depressive rumination. Depressive rumination had a positive influence on sleep disturbance and depressive symptoms, whereas sleep disturbances had a positive influence on depressive symptoms. Regarding indirect effects, depressive rumination mediated the association between parental attitudes and sleep disturbances or depressive symptoms. Furthermore, sleep disturbances mediated the association between depressive rumination and depressive symptoms. Care and overprotection showed opposite effects. The goodness of fit of this model was high., Conclusion: The results of this study demonstrated that there were associations among the four variables. Clinical assessment and intervention of depressive rumination and sleep disturbances that are closely associated with previous parental attitudes may lead to an improvement of depressive symptoms., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: Yu Tamada has received personal fees from Otsuka Pharmaceutical, Sumitomo Pharma, Eisai, MSD, and Meiji Seika Pharma. Takeshi Inoue has received personal fees from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. Jiro Masuya has received personal fees from Otsuka Pharmaceutical, Eli Lilly, Astellas, and Meiji Yasuda Mental Health Foundation, and grants from Pfizer. All other authors declare that they have no actual or potential conflicts of interest associated with this study., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study., Methods: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted., Results: The mean follow-up period was 11 years, and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR 0.73; 95% CI, 0.55-0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction., Conclusion: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

Objectives: Exploring the effects of swallowing function on sleep quality could provide valuable insights into the potential impact of reduced swallowing function on sleep. However, pertinent studies are limited. Therefore, this study aimed to investigate the relationship between dysphagia risk and sleep health in community-dwelling older adults., Methods: Data for this cross-sectional study were obtained from the Shizuoka and Daiko studies conducted as part of the Japan Multi-Institutional Collaborative Cohort Study. Information on demographics, overall lifestyle, dysphagia risk, as well as sleep quality, duration, satisfaction, and regularity, was obtained using a self-administered questionnaire. Dysphagia risk and sleep quality were assessed using the Dysphagia Risk Assessment Questionnaire for the Community-dwelling Elderly and the Japanese version of the Pittsburgh Sleep Questionnaire Index, respectively. Multivariate logistic regression, adjusted for covariates, was employed to assess the association between dysphagia risk and sleep health., Results: Among the 3058 participants (1633 males, 1425 females) aged ≥60 years, 28.0 % exhibited dysphagia risk, and 19.1 % reported poor sleep quality. Those with dysphagia risk were more likely to experience poor sleep quality than those without dysphagia risk. In male participants, dysphagia was significantly associated with poor sleep quality, unsatisfactory sleep, and sleep irregularity, but was not significantly associated with unsatisfactory or irregular sleep in female participants. The Japanese version of the Pittsburgh Sleep Questionnaire Index components-subjective sleep quality, sleep latency, sleep disturbances, and daytime dysfunction-were associated with dysphagia risk in both sexes., Conclusions: Dysphagia risk is associated with sleep quality in older individuals in Japan. Thus, preserving swallowing function may contribute to enhancing sleep quality., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Secondary healthcare data use has been increasing in the dental research field. The validity of the number of remaining teeth assessed from Japanese dental claims data has been reported in several studies, but has not been tested in the general population in Japan., Objectives: To evaluate the validity of the number of remaining teeth assessed from Japanese dental claims data and assess its predictability against subsequent health deterioration., Methods: We used the claims data of residents of a municipality that implemented oral health screening programs. Using the number of teeth in the screening records as the reference standard, we assessed the validity of the claims-based number of teeth by calculating the mean differences. In addition, we assessed the association between the claims-based number of teeth and pneumococcal disease (PD) or Alzheimer's disease (AD) in adults aged ≥65 years using Cox proportional hazards analyses., Results: Of the 10,154 participants, the mean number of teeth assessed from the claims data was 20.9, that in the screening records was 20.5, and their mean difference was 0.5. During the 3-year follow-up, PD or AD onset was observed in 10.4% (3,212/30,838) and 5.3% (1,589/30,207) of participants, respectively. Compared with participants with ≥20 teeth, those with 1-9 teeth had a 1.29 (95% confidence interval [CI]: 1.17-1.43) or 1.19 (95% CI: 1.04-1.36) times higher risk of developing PD or AD, respectively., Conclusion: High validity of the claims-based number of teeth was observed. In addition, the claims-based number of teeth was associated with the risk of PD and AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tamada 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.)

Objective: Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality., Design: We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated FFQ. The hazard ratio (HR) and 95 % confidence interval (CI) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates., Setting: The Japan Multi-Institutional Collaborative Cohort Study., Participants: A total of 80 802 participants (34 555 males and 46 247 females), aged 35-69 years., Results: During a mean follow-up of 9·0 years, we identified 2482 deaths including 1495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HR (95 % CI) in females for all-cause mortality according to the intake were 0·68 (0·55, 0·85) for intakes 1-3 times/month, 0·72 (0·57, 0·90) for 1-2 times/week and 0·69 (0·54, 0·88) for ≥ 3 times/week, compared with the rare intake. The corresponding HR (95 % CI) in females for cancer mortality were 0·72 (0·54, 0·96), 0·71 (0·53, 0·96) and 0·64 (0·46, 0·89), respectively. No statistically significant association was observed in males., Conclusions: Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females.

Purpose: Correction of a gummy smile by orthodontic treatment alone has recently become feasible with the use of miniscrews. However, the optimal treatment mechanics remain unclear. Here we cephalometrically evaluated jaw and tooth displacement in cases where a gummy smile was improved using a level anchorage system (LAS)., Methods: Sixteen patients underwent orthodontic treatment using an LAS consisting of a modified transpalatal arch and midpalatal miniscrews. Cephalometric pretreatment and posttreatment measurements were compared using the paired t‑test to determine significant skeletal and dental changes. The Mann-Whitney U test was used for nonparametric data. Spearman's rank correlation coefficient was used to evaluate correlations between different variables and the vertical change in prosthion position which was used to indicate the amount of gingival exposure., Results: The changes noted after treatment were intrusion of the maxillary first molars (P < 0.001) combined with only minor extrusion of the mandibular first molars. Suppressed extrusion of the mandibular first molars was significantly correlated with greater upward movement of the prosthion (r = 0.676, P < 0.01). Upward movement of the prosthion was also significantly correlated with intrusion of the maxillary and mandibular incisors, anterior upward movement of the maxillary occlusal plane, and an increase of the SNP angle., Conclusions: Treatment involving the combined use of miniscrews and a modified transpalatal arch resulted in intrusion of the maxillary first molars and maxillary incisors and consequently elevated the maxillary occlusal plane. The results of this study suggest that intruding the maxillary occlusal plane and minimizing mandibular molar extrusion were effective to induce autorotation of the mandible and to improve a gummy smile., (© 2022. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Rewarming therapies for accidental hypothermia (AH) include extracorporeal membrane oxygenation (ECMO) and non-ECMO related (conventional) therapies. However, there are limited data available to inform the selection of conventional rewarming therapy. The aim of the present study was to explore what patients' factors and which rewarming therapy predicted favorable prognosis., Methods: This study is a secondary analysis of the Intensive Care with Extra Corporeal membrane oxygenation Rewarming in Accidentally Severe Hypothermia (ICE-CRASH) study, a multicenter prospective, observational study conducted in Japan. Enrolled in the ICE-CRASH study were patients aged ≥18 years with a core temperature of ≤32 °C who were transported to the emergency departments of 36 tertiary care hospitals in Japan between 1 December 2019 and 31 March 2022, among whom those who were rewarmed with conventional rewarming therapy were included in the present study. Logistic regression analysis was performed with 28-day survival as the objective variable; and seven factors including age, activities of daily living (ADL) independence, sequential organ failure assessment (SOFA) score, and each rewarming technique as explanatory variables. We performed linear regression analysis to identify whether each rewarming technique was associated with rewarming rate., Results: Of the 499 patients enrolled in the ICE-CRASH study, 371 were eligible for this secondary analysis. The median age was 81 years, 50.9% were male, and the median initial body temperature was 28.8 °C. Age (odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.94-1.00) and SOFA score (OR: 0.73, 95% CI: 0.67-0.81) were associated with lower survival, whereas ADL independence (OR: 2.31, 95% CI: 1.15-4.63) was associated with higher survival. No conventional rewarming therapy was associated with 28-day survival. Hot bath was associated with a high rewarming rate (regression coefficient: 1.14, 95% CI: 0.75-1.53)., Conclusion: No conventional rewarming therapy was associated with improved 28-day survival, which suggests that background factors such as age, ADL, and severity of condition contribute more to prognosis than does the selection of rewarming technique., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults., Methods: This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by P  < 0.05., Results: In multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment., Conclusions: Dairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure., Clinical Trial Registry Number and Website Where It Was Obtained: The Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000046175., Competing Interests: This study was supported by the 10.13039/501100002241Japan Science and Technology Agency (grant numbers JPMJCE1302, JPMJCA2201, and JPMJPF2210) and Megmilk Snow Brand Co., Ltd. (approval number 2022-30444). A.N., D.K., and H.M.U. are employees of the Megmilk Snow Brand. The Megmilk Snow Brand funded the Department of Precision Nutrition for Dairy Foods at Hirosaki University and provided human resources and infrastructure for this study. The Megmilk Snow Brand manufactures and sells dairy foods in Japan and some Asian and Oceanian countries. The other authors declare no conflicts of interest., (© 2024 The Authors.)

Background: The influence of the coronavirus disease (COVID-19) pandemic on dental care utilization may have differed according to individual characteristics or type of dental care provision. This study aimed to evaluate the changes in dental care utilization and per-attendance costs by age group and type of dental care during the COVID-19 pandemic in Japan., Methods: This time-series study used healthcare insurance claims data from 01/07/2019 to 09/27/2021 (143 weeks) from nine municipalities in Japan. Dental care utilization rate per week and average dental care cost per attendance by age groups (0-19y/20-64y/65-74y/≥ 75y) and types of dental care (outpatient/visiting) were used as outcome variables. COVID-19 pandemic waves in Japan were used as predictors: 1 st (03/23/2020-05/17/2020), 2 nd (06/22/2020-09/27/2020), 3 rd (10/26/2020-02/21/2021), 4 th (02/22/2021-06/07/2021), and 5 th (07/05/2021-09/13/2021) waves. Fixed effect models were employed to estimate the proportional changes., Results: In the fixed effect model, we observed large declines in dental care utilization during the 1 st (17.0-22.0%) and 2 nd waves (3.0-13.0%) compared to the non-pandemic wave period in all age groups. In contrast, the average dental care cost per attendance increased in all age groups by 5.2-8.6% during the 1 st wave., Conclusions: During the initial wave of the COVID-19 pandemic in Japan, dental care utilization decreased in all age groups, whereas the average dental care cost per attendance increased. The COVID-19 pandemic may have changed the dental care provision pattern towards less frequent and more concentrated dental care to avoid the risk of infection.

Background: Few prospective studies have examined the association between social disconnection and late-life suicide. Therefore, we conducted a large-scale prospective study of older adults in Japan to examine differences in suicide mortality according to specific aspects of social disconnectedness., Methods: We conducted a nationwide baseline survey of functionally independent older adults (age ≥65 years) from 12 municipalities in Japan from 2010 to 2011. We followed the participants (n = 46,144) for cause of death through December 2017 using vital statistics. Social disconnection was assessed based on the indicators of eating alone, a lack of instrumental/emotional support, no participation in community activities, and no contact with friends. We adopted Cox regression models with multiple imputation for missing values and calculated the population-attributable fraction (PAF)., Results: A total of 55 suicide deaths were recorded during an average follow-up of 7 years. Older adults with social disconnection had a marginally increased risk of suicide. The hazard ratio for eating alone vs. eating together was 2.81 (95% confidence interval [CI]: 1.47-5.37). The direction of these associations and point estimations did not largely change after controlling for depressive symptoms, an evident risk factor for suicidal behavior. The PAF indicated that eating alone was attributable to around 1800 (29%) of the suicide deaths among older adults annually in Japan., Conclusion: Avoidance of not only depressive symptoms, but also social disconnection including eating alone, is useful in suicide prevention among older adults., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hakutsurunishiki is a sake rice cultivar bred using Yamadabo (seed parent) and Wataribune 2 (pollen parent), equivalent to a Yamadanishiki sibling. This study evaluated the structural characteristics of the Hakutsurunishiki rice grain that contribute to the brewing characteristics of daiginjo-shu, via a comparison with Yamadanishiki. Hakutsurunishiki brown rice was a little heavy and had a large white core. Observing a cross-section of white rice after soaking revealed that the rice grain structure of Hakutsurunishiki was different from that of Yamadanishiki. Hakutsurunishiki white rice showed fewer voids than Yamadanishiki, promoting a slower water absorption rate. Glucose distribution in rice koji obtained by mass spectrometry imaging showed that Hakutsurunishiki rice koji, like Yamadanishiki, is tsuki-haze type, suggesting that its grain structure is suitable for making rice koji for daiginjo-shu. With these observations, we were able to clarify the structural characteristics of Hakutsurunishiki rice grain., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut microbiota and muscle strength indicators using grip strength/BMI in a large-scale study of community residents. The mean age of men ( n = 442) and women ( n = 588) was 50.5 (15.3) and 51.2 (15.9) years, respectively. The muscle strength indicator used was grip/BMI. The association between total read count and genus-level gut microbiota and muscle strength was analyzed. The mean grip/BMI was 1.8 (0.3) for men and 1.2 (0.2) for women. The genus of the gut microbiota that showed an association in both sexes was Eggerthella (men: β = 0.18, CI: 0.04-0.31, p = 0.009; women: β = 0.07, CI: 0.00-0.12, p = 0.028). Blautia , Eggerthella and Faecalibacterium were found to be significantly associated with grip/BMI in both the multiple regression analysis and Spearman's correlation analysis after the multiple comparison adjustment. These results suggest that an increase in Blautia and Eggerthella , coupled with a decrease in Faecalibacterium , may contribute to muscle strengthening or the suppression of muscle weakness.

Aim: Tooth loss has various causes; however, its cause-specific effects on health outcomes remain unclear. This study evaluated whether the association between past/current smoking and risk of dementia was mediated by tooth loss., Materials and Methods: This 9-year-follow-up prospective cohort study targeted adults aged ≥65 years. Dementia incidence during 2013-2019, smoking status (never, past/current) in 2010 and the number of remaining teeth (≤19, ≥20) in 2013 were the outcome, exposure and mediator, respectively. We used causal mediation analysis to fit the Cox proportional hazards model and estimated the hazard ratio (HR) and 95% confidence interval (CI) of the natural indirect effect (NIE) of smoking on dementia incidence through tooth loss and their mediated proportions., Results: Among 32,986 participants (mean age 72.6 years [1 SD = 5.4]; men 48.4%), the dementia incidence during follow-up was 2.11/100 person-years. Tooth loss significantly mediated the association between past/current smoking and dementia incidence; the NIE of fewer remaining teeth for past/current smokers compared to never smokers was HR = 1.03 (95% CI: 1.02-1.05), and the mediated proportion was 18.0%., Conclusions: Tooth loss significantly mediates the association between past/current smoking and an increased risk of dementia among older adults., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Bivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan., Methods: We adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 - odds ratio) × 100%., Results: A total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14-20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults., Conclusions: Bivalent vaccines are effective against COVID-19 infections among older adults without a history of infection., (© 2024. The Author(s).)

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by severe lung fibrosis and a poor prognosis. Although the biomolecules related to IPF have been extensively studied, molecular mechanisms of the pathogenesis and their association with serum biomarkers and clinical findings have not been fully elucidated. We constructed a Bayesian network using multimodal data consisting of a proteome dataset from serum extracellular vesicles, laboratory examinations, and clinical findings from 206 patients with IPF and 36 controls. Differential protein expression analysis was also performed by edgeR and incorporated into the constructed network. We have successfully visualized the relationship between biomolecules and clinical findings with this approach. The IPF-specific network included modules associated with TGF-β signaling (TGFB1 and LRC32), fibrosis-related (A2MG and PZP), myofibroblast and inflammation (LRP1 and ITIH4), complement-related (SAA1 and SAA2), as well as serum markers, and clinical symptoms (KL-6, SP-D and fine crackles). Notably, it identified SAA2 associated with lymphocyte counts and PSPB connected with the serum markers KL-6 and SP-D, along with fine crackles as clinical manifestations. These results contribute to the elucidation of the pathogenesis of IPF and potential therapeutic targets., (© 2024. The Author(s).)

Complex structures in living cells and tissues induce wavefront errors when light waves pass through them, and images observed with optical microscopes are undesirably blurred. This problem is especially serious for living plant cells because images are strikingly degraded even within a single cell. Adaptive optics (AO) is expected to be a solution to this problem by correcting such wavefront errors, thus enabling high-resolution imaging. In particular, scene-based AO involves wavefront sensing based on the image correlation between subapertures in a Shack-Hartmann wavefront sensor and thus does not require an intense point light source. However, the complex 3D structures of living cells often cause low correlation between subimages, leading to loss of accuracy in wavefront sensing. This paper proposes a novel method for scene-based sensing using only image correlations between adjacent subapertures. The method can minimize changes between subimages to be correlated and thus prevent inaccuracy in phase estimation. Using an artificial test target mimicking the optical properties of a layer of living plant cells, an imaging performance with a Strehl ratio of approximately 0.5 was confirmed. Upon observation of chloroplast autofluorescence inside living leaf cells of the moss Physcomitrium patens, recovered resolution images were successfully obtained even with complex biological structures. Under bright-field illumination, the proposed method outperformed the conventional method, demonstrating the future potential of this method for label- and damage-free AO microscopy. Several points for improvement in terms of the effect of AO correction are discussed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The influence of psychosocial factors on differentiating between melancholic depression (MEL) and non-melancholic depression (NMEL) remains unclear. In this study, we aimed to investigate the interrelationship between dysfunctional parenting, personality traits, stressful life events, and the diagnosis of MEL and NMEL among patients with major depressive disorder (MDD)., Methods: Ninety-eight patients with MDD completed the following self-administered questionnaires: the Parental Bonding Instrument (PBI) for dysfunctional parenting, the short version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) for affective temperaments, and the Life Experiences Survey (LES) for stressful life events. The data were analyzed using single and multiple regression analyses and path analysis., Results: Dysfunctional parenting did not have a significant direct effect on MEL. However, paternal care had a significant indirect effect on MEL through depressive temperament. The total indirect effect of paternal care on MEL was significant (indirect path coefficient = 0.161, p <0.05). In other words, low levels of paternal care were associated with the development of NMEL via increased depressive temperament. None of the paths from paternal care to MEL via negative change scores of the LES were significant., Limitations: This study used cross-sectional data, so the possibility that current depressive status may affect the assessment of LES and TEMPS-A cannot be ruled out., Conclusions: We found that low levels of paternal care did not directly affect the development of NMEL, but affected the development of NMEL through the mediation of depressive temperament rather than stressful life events., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: YT received honoraria from Otsuka Pharmaceutical, Sumitomo Pharma, Eisai, MSD and Meiji Seika Pharma. TI has received personal compensation from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. AS has received personal compensation from Otsuka Pharmaceutical, Meiji Seika Pharma, Takeda Pharmaceutical, and Sumitomo Pharma. HT has received lecture fees from Sumitomo Pharma, Otsuka Pharmaceutical, Takeda Pharmaceutical, Pfizer, Yoshitomi Pharmaceutical, and Viatris. MT has received lecture fees from Kyowa Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, Takeda Pharmaceutical, and Lundbeck. MS has received lecture fees from Viatris. YF has received honoraria from Sumitomo Pharma, and research grants from Shionogi and Sumitomo Pharma. SO has received honoraria from Viatris and Takeda Pharmaceutical. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Tamada 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.)

The development of useful biomaterials has resulted in significant advances in various fields of science and technology. The demand for new biomaterial designs and manufacturing techniques continues to grow, with the goal of building a sustainable society. In this study, two types of DNA-cationic surfactant complexes were synthesized using commercially available deoxyribonucleic acid from herring sperm DNA (hsDNA, <50 bp) and deoxyribonucleic acid from salmon testes DNA (stDNA, ~2000 bp). The DNA-surfactant complexes were blended with a polylactic acid (PLA) biopolymer and electrospun to obtain nanofibers, and then copper nanoparticles were synthesized on nanofibrous webs. Scanning electron microscopic images showed that all nanofibers possessed uniform morphology. Interestingly, different diameters were observed depending on the base pairs in the DNA complex. Transmission electron microscopy showed uniform growth of copper nanoparticles on the nanofibers. Fourier-transform infrared spectroscopy spectra confirmed the uniform blending of both types of DNA complexes in PLA. Both stDNA- and hsDNA-derived nanofibers showed greater biocompatibility than native PLA nanofibers. Furthermore, they exerted significant antibacterial activity in the presence of copper nanoparticles. This study demonstrates that DNA is a potentially useful material to generate electrospun nanofibrous webs for use in biomedical sciences and technologies., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Laughter has a protective effect on human health. The spread of coronavirus disease 2019 (COVID-19) has changed opportunities for face-to-face communication and might decrease opportunities for laughter. This cross-sectional study aimed to investigate whether the decrease in face-to-face communication during the COVID-19 pandemic is associated with a decrease in laughter. Additionally, we investigated whether an increase in online communication mitigates this association. Data from the "Japan COVID-19 and Society Internet Survey (JACSIS)," conducted between August and September 2020, were used. Participants aged 15-79 years were included in this study. The outcome was a decrease in laughter before the onset of the COVID-19 pandemic. The explanatory variables were decreased face-to-face communication with friends and increased online communication (text message, telephone, and video contact). Causal mediation analysis was used to calculate prevalence ratios (PRs) and 95 % confidence intervals (CIs) of the controlled direct effects of increased online communication. Furthermore, the proportions eliminated (PEs) by an increase in online communication were calculated. Among the 25,482 participants, 40.4 % had decreased face-to-face communication and 21.4 % had a decreased frequency of laughter. After adjusting for confounders, a decrease in face-to-face communication was significantly associated with a decrease in laughter (PR = 1.62, 95 %CI = 1.55-1.70). PEs for decrease in laughter were 27.2 % (95 %CI = -2.0 to 56.4) for text-based communication, 36.1 % (95 %CI = 12.3-59.8) for telephone-based communication, and 28.6 % (95 %CI = 0.6-56.6) for video-based communication. Although a decrease in face-to-face communication was associated with a decrease in laughter during the COVID-19 pandemic, online communication, particularly telephone-based communication, mitigated this association., Competing Interests: 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., (© 2023 The Authors.)

Aim: The risk of falls owing to simultaneous use of multiple hypnotics has not been clarified. The aim of this study was to assess the association between the simultaneous use of 2 hypnotics and the occurrence of falls in hospitalized patients., Methods: A matched case-control study was conducted at Tokyo Medical University Hospital in Tokyo, Japan, utilizing data from medical records. Cases were 434 hospitalized patients who experienced falls during their hospital stay between January 2016 and December 2016, and controls were 434 hospitalized patients without falls, individually matched by age, sex, and clinical department. The outcome was the occurrence of an in-hospital fall. The associations between the use of 1 hypnotic and falls, and between the use of 2 hypnotics and falls were assessed by conditional logistic regression analyses. The main multivariable conditional logistic regression model was adjusted for potential risk factors, including the use of other classes of psychotropics (antipsychotics, antidepressants, and anxiolytics), in addition to patient characteristics., Results: The main multivariable conditional logistic regression analyses showed that the simultaneous use of 2 hypnotics (odds ratio [OR] = 2.986; 95% confidence interval [CI], 1.041-8.567), but not the use of a single hypnotic (OR = 1.252; 95% CI, 0.843-1.859), was significantly associated with an increased OR of falls., Conclusion: The simultaneous use of 2 hypnotics is a risk factor for falls among hospitalized patients, whereas the use of a single hypnotic may not., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Akiyoshi Shimura has received personal fees from Dainippon Sumitomo Pharma and Eisai. Jiro Masuya has received personal fees from Otsuka Pharmaceutical, Eli Lilly, Astellas, and Meiji Yasuda Mental Health Foundation, and grants from Pfizer. Shinji Higashi has received personal fees from Dainippon Sumitomo Pharma and Novartis Pharma. Takeshi Inoue is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma, and has received personal fees from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal fees from Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma. Yota Fujimura has received research and grant support from Novartis Pharma, Otsuka Pharmaceutical, Astellas, Dainippon Sumitomo Pharma, and Shionogi. The other authors have no actual or potential conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Morishita 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.)

COVID-19 remains a global health threat. Compliance with nonpharmaceutical interventions is essential because of limited effectiveness of COVID-19 vaccines, emergence of highly contagious variants, and declining COVID-19 antibody titers over time. We evaluated compliance with 14 nonpharmaceutical intervention-related COVID-19 preventive behaviors, including mask wearing, ventilation, and surface sanitation, in a longitudinal study in Japan using 4 waves of Internet survey data obtained during 2020-2022. Compliance with most preventive behaviors increased or remained stable during the 2-year period, except for surface sanitation and going out behaviors; compliance with ventilation behavior substantially decreased in winter. Compliance patterns identified from latent class analysis showed that the number of persons in the low compliance class decreased, whereas those in the personal hygiene class increased. Our findings reflect the relaxation of mobility restriction policy in Japan, where the COVID-19 pandemic continues. Policymakers should consider behavioral changes caused by new policies to improve COVID-19 prevention strategies.

Abstract: The association between major depressive disorder (MDD) and personality traits has been extensively studied. However, differences in personality traits between patients with melancholic MDD (MEL) and nonmelancholic MDD (NMEL) remain unclear. In this study, we aimed to determine whether neuroticism, which has been associated with MDD, and the five affective temperament subtypes assessed by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) can be used to distinguish MEL and NMEL. A total of 106 patients with MDD (MEL, n = 52; NMEL, n = 54) and 212 age- and sex-matched healthy controls answered the Eysenck Personality Questionnaire-revised and the short version of TEMPS-A. In hierarchical logistic regression analysis, only depressive temperament scores were identified as a statistically significant feature distinguishing NMEL from MEL. Depressive temperament scores assessed by the short version of TEMPS-A were found to be significantly higher in NMEL patients than in MEL patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Although the effectiveness of coronavirus disease 2019 (COVID-19) vaccines is a crucial public health concern, evidence from Western Pacific countries is limited, including Japan. This study aimed to estimate the COVID-19 vaccines effectiveness (VE) against infection during the Delta variant predominance (July-September 2021) in Japan., Methods: We performed a test-negative study using COVID-19 test data of ≥20-year-old residents in four municipalities who were tested in medical institutions between July 1 and September 30, 2021. We extracted COVID-19 test data from healthcare claims data, and the vaccination status at the testing date was ascertained using the Vaccination Record System data. Confirmed positive cases were identified using data from the national system for COVID-19, Health Center Real-time Information-sharing System on COVID-19. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. VE was calculated as (1 - odds ratio) × 100%., Results: This study included 530 positive and 15,650 negative results. Adjusted manufacturer-unspecified VE was 4.1% (95% confidence interval [CI], -36.5-32.6) at 0-13 days after the first dose, 45.2% (95% CI, 13.4-65.3) at ≥14 days after the first dose, 85.2% (95% CI, 69.9-92.7) at 0-13 days after the second dose, and 79.6% (95% CI, 72.6-84.8) at ≥14 days after the second dose. In addition, the VE after the second dose was highest at 14-34 days after the dose (VE, 89.1%; 95% CI, 80.5-93.9)., Conclusions: High real-world effectiveness of COVID-19 vaccines, especially two doses, against infection during the Delta variant predominance in Japan was confirmed., 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 © 2023 Elsevier Ltd. All rights reserved.)

Although altered networks inside the hippocampus (hippocampal intra-networks) have been observed in dementia, the evaluation of hippocampal intra-networks using magnetic resonance imaging (MRI) is challenging. We employed conventional structural imaging and incident component analysis (ICA) to investigate the structural covariance of the hippocampal intra-networks. We aimed to assess altered hippocampal intra-networks in patients with mild cognitive impairment (MCI). A cross-sectional study of 2122 participants with 3T MRI (median age 69 years, 60.9% female) were divided into 218 patients with MCI and 1904 cognitively normal older adults (CNOA). By employing 3D T1-weighted imaging, voxels within the hippocampus were entered into the ICA analysis to extract the structural covariance intra-networks within the hippocampus. The ICA extracted 16 intra-networks from the hippocampal structural images, which were divided into two bilateral networks and 14 ipsilateral networks. Of the 16 intra-networks, two (one bilateral network and one ipsilateral networks) were significant predictors of MCI from the CNOA after adjusting for age, sex, education, disease history, and hippocampal volume/total intracranial volume ratio. In conclusion, we found that the relationship between hippocampal intra-networks and MCI was independent from the hippocampal volume. Our results suggest that altered hippocampal intra-networks may reflect a different pathology in MCI from that of brain atrophy., (© 2023. Springer Nature Limited.)

Aim: Understanding the appropriate prescription of psychotropics for hospitalized patients in terms of preventing falls is an important issue. The aim of this study was to assess the associations between the occurrence of falls and the use of various individual psychotropics in hospitalized patients., Methods: A retrospective matched case-control study was conducted on adult patients admitted to every department of Tokyo Medical University Hospital, with the outcome being in-hospital falls. A total of 447 hospitalized patients who had had in-hospital falls at some point in their hospitalization between January 2016 and December 2016 were included as cases. A total of 447 hospitalized patients who did not have in-hospital falls, and were individually matched to the cases by sex, age, and clinical department, were included as controls. All data were extracted from electronic medical records. Conditional logistic regression analyses were conducted to assess the association between the exposure to 16 psychotropic medications and the occurrence of in-hospital falls. The multivariable logistic regression model adjusted sex, age, clinical department, body mass index, fall risk score on the fall risk assessment measure, and use of psychotropic medications., Results: The multivariable conditional logistic regression model showed a significant association between the use of risperidone (odds ratio [OR] = 3.730; 95% confidence interval [CI] = 1.229-11.325) and flunitrazepam (OR = 4.120; 95% CI = 1.105-15.364) and an increased OR of falls among hospitalized patients., Conclusion: The use of risperidone and flunitrazepam were identified as risk factors for falls among hospitalized patients., Competing Interests: Jiro Masuya has received personal fees from Otsuka Pharmaceutical, Eli Lilly, Astellas, MSD, Janssen Pharmaceutical, Takeda Pharmaceutical, Shionogi Pharmaceutical, and Meiji Yasuda Mental Health Foundation, as well as grants from Pfizer, and Mitsubishi Tanabe Pharma. Yu Tamada has received honoraria from Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, and Eisai. Yota Fujimura has received honoraria and a research grant from Sumitomo Pharma, and research grants from Otsuka Pharmaceutical, and Shionogi. Takeshi Inoue is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma, and has received personal fees from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal fees from Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma. The other authors have no actual or potential conflicts of interest to declare., (© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Aim: Productivity loss in the workplace due to physical or mental health problems, which is called presenteeism, leads to large financial losses. Personal and work environment factors, as well as physical and mental illnesses are associated with presenteeism, but the detailed underlying mechanism remains unclear. In this study, we analyzed the effects of perceived childhood rearing on the presenteeism of adult workers, and the mediating effects of trait anxiety and depressive rumination., Methods: In 2017 and 2018, a cross-sectional paper-based survey was conducted, and written consent from 447 adult workers was obtained. Demographic information and results from the Parental Bonding Instrument, trait anxiety of State-Trait Anxiety Inventory Form Y, Ruminative Responses Scale, and Work Limitations Questionnaire were surveyed. Multiple regression analyses and structural equation modeling were conducted., Results: The low perceived quality of rearing from parents in childhood, i.e., low care and high overprotection, indirectly worsened current presenteeism via trait anxiety and depressive rumination. Presenteeism was directly worsened by trait anxiety and depressive rumination, and the low perceived quality of rearing from parents directly affected trait anxiety and depressive rumination, and trait anxiety affected depressive rumination., Conclusion: The results of this study clarified the long-term influences of the low perceived quality of rearing experienced in childhood on adulthood presenteeism via trait anxiety and depressive rumination. Therefore, assessing the quality of childhood rearing, trait anxiety, and depressive rumination of individuals may help to elucidate the causes of presenteeism in the workplace, and how to manage it effectively., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Yota Fujimura has received personal compensation from Sumitomo Pharma, and grants from Otsuka Pharmaceutical, Sumitomo Pharma, and Shionogi. Takeshi Inoue has received personal compensation from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. Jiro Masuya has received personal compensation from Otsuka Pharmaceutical, Eli Lilly, Astellas, and Meiji Yasuda Mental Health Foundation, and grants from Pfizer. All other authors declare that they have no actual or potential conflicts of interest associated with this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Shimasaki 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.)

Introduction: The population-attributable risk of oral status for incident functional disability remains unknown. We investigated the impact of a range of oral statuses (number of remaining teeth, chewing difficulty, dry mouth, and choking) on incident functional disability., Methods: Participants (n = 44,083) aged ≥ 65 years from the Japan Gerontological Evaluation Study were evaluated. The outcome variable was incident functional disability, and the explanatory variables were four select oral statuses. The possible confounders were included as covariates. Using the Cox proportional hazards model, we calculated hazard ratios (HRs), 95% confidence intervals (CIs), and their population-attributable fractions (PAFs)., Results: The mean age of the participants was 73.7 (standard deviation=6.0) years at baseline, and 53.2% were women. A total of 8,091 participants (18.4%) developed functional disabilities during the follow-up period. Among the four oral statuses, the incidence rate of functional disability was the highest in those with chewing difficulty (3.27/100 person-years), followed by those with dry mouth (3.20/100 person-years), choking (3.10/100 person-years), and ≤19 remaining teeth (2.89/100 person-years). After adjusting for all covariates, chewing difficulty showed the highest risk of functional disability (HR=1.22, 95%CI=1.16-1.28), followed by ≤19 remaining teeth (HR=1.18, 95%CI=1.12-1.25), dry mouth (HR=1.18, 95%CI=1.12-1.24), and choking (HR=1.10, 95%CI=1.04-1.17). Regarding PAF, ≤19 remaining teeth (12.0%) were the largest, followed by chewing difficulty (7.2%), dry mouth (4.6%), and choking (1.9%)., Conclusions: Maintaining a good oral status may reduce the risk of functional disability later in life. Given its population contribution, tooth loss had the largest impact among the four oral conditions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Early disease detection and prevention methods based on effective interventions are gaining attention worldwide. Progress in precision medicine has revealed that substantial heterogeneity exists in health data at the individual level and that complex health factors are involved in chronic disease development. Machine-learning techniques have enabled precise personal-level disease prediction by capturing individual differences in multivariate data. However, it is challenging to identify what aspects should be improved for disease prevention based on future disease-onset prediction because of the complex relationships among multiple biomarkers. Here, we present a health-disease phase diagram (HDPD) that represents an individual's health state by visualizing the future-onset boundary values of multiple biomarkers that fluctuate early in the disease progression process. In HDPDs, future-onset predictions are represented by perturbing multiple biomarker values while accounting for dependencies among variables. We constructed HDPDs for 11 diseases using longitudinal health checkup cohort data of 3,238 individuals, comprising 3,215 measurement items and genetic data. The improvement of biomarker values to the non-onset region in HDPD remarkably prevented future disease onset in 7 out of 11 diseases. HDPDs can represent individual physiological states in the onset process and be used as intervention goals for disease prevention., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risks of mortality., Objectives: We examined long-term associations of carbohydrate and fat intakes with mortality., Methods: In this cohort study, 34,893 men and 46,440 women aged 35-69 y (mean body mass index of 23.7 and 22.2 kg/m 2 , respectively) were followed up from the baseline survey (2004-2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percentage of energy intakes of carbohydrate and fat., Results: During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to <55% of energy from carbohydrate, those who consumed <40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19-2.12; P-trend = 0.002). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93-3.13) for ≥65% of energy from carbohydrate compared with that for 50% to <55% (P-trend = 0.005). Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11-2.90) compared with that for 20% to <25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively)., Conclusions: An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies reported that the experience of maltreatment in childhood reduces subjective well-being in adulthood and that neuroticism is negatively associated with subjective well-being. However, the interrelationship between childhood maltreatment, adult life events, neuroticism, and subjective well-being has not been analyzed to date., Methods: A total of 404 adult volunteers provided responses to the following questionnaires: 1) Childhood Abuse and Trauma Scale, 2) Life Experiences Survey, 3) Neuroticism Subscale of the Shortened Eysenck Personality Questionnaire-Revised, and 4) Subjective Well-Being Inventory. The path model was used to analyze possible interrelationships among these parameters., Results: The effect of childhood abuse on subjective well-being was indirect and was mediated by neuroticism. The effect of neuroticism on the negative, but not positive, change score on the Life Experiences Survey was significant. The indirect effect of neuroticism on subjective well-being was not significant via either negative or positive change scores., Conclusions: This study demonstrated that age, subjective social status, neuroticism, and negative and positive life events were significantly associated with subjective well-being. Furthermore, using path analysis, we demonstrated the mediating role of neuroticism in the indirect effect of childhood abuse on subjective well-being., (© 2023. The Author(s).)

Background: Personality traits, such as neuroticism, that results in vulnerability to stress, and resilience, a measure of stress coping, are closely associated with the onset of depressive symptoms, whereas regular physical activity habits have been shown to reduce depressive symptoms. In this study, the mediating effects of neuroticism and resilience between physical activity duration and depressive symptoms were investigated by a covariance structure analysis., Methods: Between April 2017 and April 2018, 526 adult volunteers were surveyed using self-administered questionnaires. Demographic information, habitual physical activity duration (PAD), neuroticism, and resilience were investigated. The effects of these factors on depressive symptoms were analyzed by a covariance structure analysis. This study was conducted with the approval of the Medical Ethics Committee of Tokyo Medical University., Results: The dose-response curves of physical activity duration and depression scores were U-shaped: the optimal physical activity duration for the lowest depression score was 25.7 h/week. We found that the greater the difference from the optimal PAD, the higher the neuroticism and the lower the resilience, and the more severe the depressive symptoms. Covariance structure analysis demonstrated that neuroticism and resilience significantly and completely mediated the effects of the difference from the optimal PAD on depressive symptoms (coefficient of determination R 2 = 0.349)., Conclusion: Our study suggests that there is an optimal PAD that reduces depressive symptoms, and that a greater difference from the optimal PAD increases depressive symptoms through neuroticism and resilience.

Multicellular organisms rely on intercellular communication systems to organize their cellular functions. In studies focusing on intercellular communication, the key experimental techniques include the generation of chimeric tissue using transgenic DNA recombination systems represented by the CRE/ loxP system. If an experimental system enables the induction of chimeras at highly targeted cell(s), it will facilitate the reproducibility and precision of experiments. However, multiple technical limitations have made this challenging. The stochastic nature of DNA recombination events, especially, hampers reproducible generation of intended chimeric patterns. Infrared laser-evoked gene operator (IR-LEGO), a microscopic system that irradiates targeted cells using an IR laser, can induce heat shock-mediated expression of transgenes, for example, CRE recombinase gene, in the cells. In this study, we developed a method that induces CRE/ loxP recombination in the target cell(s) of plant roots and leaves in a highly specific manner. We combined IR-LEGO, an improved heat-shock-specific promoter, and dexamethasone-dependent regulation of CRE. The optimal IR-laser power and irradiation duration were estimated via exhaustive irradiation trials and subsequent statistical modeling. Under optimized conditions, CRE/ loxP recombination was efficiently induced without cellular damage. We also found that the induction efficiency varied among tissue types and cellular sizes. The developed method offers an experimental system to generate a precisely designed chimeric tissue, and thus, will be useful for analyzing intercellular communication at high resolution in roots and leaves., 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 © 2023 Tomoi, Tameshige, Betsuyaku, Hamada, Sakamoto, Uchida, Torii, Shimizu, Tamada, Urawa, Okada, Fukuda, Tatematsu, Kamei and Betsuyaku.)

Decreased swallowing function increases the risk of choking and aspiration pneumonia. Videofluoroscopy and computed tomography allow for detailed observation of the swallowing movements but have radiation risks. Therefore, we developed a method using surface electromyography (sEMG) to noninvasively assess swallowing function without radiation exposure. A 44-channel flexible sEMG sensor was used to measure the sEMG signals of the hyoid muscles during swallowing in 14 healthy young adult and 14 elderly subjects. Muscle synergy analysis was performed to extract the muscle synergies from the sEMG signals, and the three synergies were extracted from the hyoid muscle activities during the swallowing experiments. The experimental results showed that the three synergies represent the oral, early pharyngeal, and late pharyngeal swallowing phases and that swallowing strength is tuned by the strength of the muscle activities, whereas swallowing volume is controlled by adjusting muscle activation timing. In addition, the timing of the swallowing reflex is slower in elderly individuals. The results confirm that the proposed approach successfully quantifies swallowing function from sEMG signals, mapping the signals to the swallowing phases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Bipolar disorder is a leading disorder contributing to global disease burden, and bipolar depression often becomes severe and refractory. Therefore, clarifying the pathophysiology of bipolar disorder is an urgent issue. Previous reports suggested that factors, such as affective temperaments and childhood maltreatment, aggravate bipolar depression severity. However, to our knowledge, no reports to date have clarified the interrelationship between the above factors and bipolar depression severity. We here hypothesized that childhood maltreatment worsens bipolar depression severity via increasing affective temperaments. To test this hypothesis, a covariance structural analysis was conducted., Methods: The following information was evaluated for a total of 75 people with bipolar disorder using self-administered questionnaires: demographic characteristics, depressive symptoms (Patient Health Questionnaire-9), history of childhood maltreatment (Child Abuse and Trauma Scale), and affective temperaments (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire). The results were analyzed using covariance structure analysis., Results: A significant indirect effect of childhood maltreatment on bipolar depression severity via increasing affective temperaments was identified, whereas the direct effect of childhood maltreatment was not significant., Conclusion: Our results reveal that affective temperaments can mediate the adverse effects of childhood maltreatment on the severity of bipolar depression., Competing Interests: Jiro Masuya has received personal compensation from Otsuka Pharmaceutical, Eli Lilly, Astellas, and Meiji Yasuda Mental Health Foundation, and grants from Pfizer. Yota Fujimura has received research and grant support from Novartis Pharma, Otsuka Pharmaceutical, Astellas, Dainippon Sumitomo Pharma, and Shionogi. Shinji Higashi has received honoraria from Dainippon Sumitomo Pharma and Novartis Pharma. Takeshi Inoue has received personal compensation from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. Ichiro Kusumi has received personal compensation from Astellas, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Nippon Chemiphar, Novartis Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Mitsubishi Tanabe Pharma, Shionogi, and Yoshitomiyakuhin; has received research/grant support from AbbVie GK, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Takeda Pharmaceutical, Tanabe Mitsubishi Pharma, Shionogi, and Yoshitomiyakuhin; and is a member of the advisory boards of Dainippon Sumitomo Pharma and Tanabe Mitsubishi Pharma. The other authors declare that they have no actual or potential conflicts of interest associated with this study. Yu Tamada received honoraria from Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, and Eisai., (© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults., Methods: A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy ("sometimes," and "often/very often" use versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated., Results: During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs for "sometimes" were 0.81 (95% confidence interval [CI], 0.67-0.97) for emotional expression, 0.79 (95% CI, 0.66-0.95) for emotional support-seeking, and 0.80 (95% CI, 0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (P for interaction = 0.03)., Conclusion: In a large Japanese sample, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.

Daily dietary habits directly or indirectly influence the intestinal microbiota, and the resulting changes in its composition and metabolic activity alter the health conditions of the host. Although many studies have analyzed the association between individual nutrients/food items and intestinal microbiota, the assessment of the diet and intestinal microbiota from a macroscopic perspective has not yet been performed in Japan. Therefore, we focused on vegetables and fruits and aimed to identify dietary patterns of high intake of these foods and to examine their relationship with the intestinal microbiota. This cross-sectional study included 1019 healthy individuals aged ≥20 years in a rural area in northern Japan. Six dietary patterns were detected by factor analysis using the brief-type self-administered diet history questionnaire (BDHQ) data to identify the "vege pattern", which was the dietary pattern rich in vegetables and fruits. Permutational multivariate analysis of variance revealed changes in β-diversity according to dietary patterns. In multivariable-adjusted models, the adherence to the vege pattern was positively correlated with α-diversity. This is the first study to reveal a correlation between intestinal microbiota and dietary habits rich in vegetables and fruits in a rural area of Japan.

Background: Previous studies have reported that physical activity can prevent the onset of depression and reduces anxiety. In the present study, the hypothesis that total physical activity time influences depressive symptoms via state and trait anxiety was tested by a path analysis., Methods: Self-administered questionnaires were used to survey 526 general adult volunteers from April 2017 to April 2018. Demographic information, physical activity, and state and trait anxiety were investigated., Results: The association between physical activity time and depressive symptoms was expressed as a U-shape curve. The results of the covariance structure analysis showed that differences from the optimal physical activity time (DOT) had direct positive effects on state and trait anxiety. DOT affected depressive symptoms only via trait anxiety, and this was a complete mediation model., Conclusion: The present study suggests that an optimal physical activity time exists for depressive symptoms. The path model demonstrated an association between the three factors of optimal physical activity time, trait anxiety, and depressive symptoms, and the effect was fully mediated by trait anxiety.

A simple method by which the functional peptide of Gly-Arg-Gly-Asp-Ser (GRGDS) is immobilized on the surface of silk fibroin (SF) films via Gly-Ala-Gly-Ala-Gly-Ser (GAGAGS) sequences is proposed. GAGAGS, a repeating amino acid sequence in the crystal region of Bombyx mori SF, performs a key role in interacting with and immobilizing SF molecules. Immobilization by this proposed method involves no chemical reaction, thereby preserving the original properties of the SF molecule. The density of GRGDS peptides existing on SF film was found to be higher in the GAGAGS-bound type than in the non-GAGAGS-bound type. Furthermore, results showed that the amount of immobilized (GAGAGS)GRGDS peptide increased as the β-sheet crystallization was promoted in the SF film. Fibroblasts, which adhered to the surface of the SF film, showed more extensibility because of the (GAGAGS)GRGDS immobilization, which suggests that the cell adhesion activity of RGD is functioning effectively., (© 2022 Wiley-VCH GmbH.)

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs., Competing Interests: Declaration of competing interest Tetsuya Matsumoto received speaker honoraria from MSD K·K., and Pfizer Japan Inc., Intestu Kobayashi received scholarship donations from Nippon Becton Dickinson Company, Ltd., Tatsuyoshi Kawamura speaker honoraria from Maruho Co., Ltd., and Eli Lilly Japan K.K. and received scholarship donations from AbbVie GK., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Plant cells are surrounded by a cell wall and do not migrate, which makes the regulation of cell division orientation crucial for development. Regulatory mechanisms controlling cell division orientation may have contributed to the evolution of body organization in land plants. The GRAS family of transcription factors was transferred horizontally from soil bacteria to an algal common ancestor of land plants. SHORTROOT ( SHR ) and SCARECROW ( SCR ) genes in this family regulate formative periclinal cell divisions in the roots of flowering plants, but their roles in nonflowering plants and their evolution have not been studied in relation to body organization. Here, we show that SHR cell autonomously inhibits formative periclinal cell divisions indispensable for leaf vein formation in the moss Physcomitrium patens , and SHR expression is positively and negatively regulated by SCR and the GRAS member LATERAL SUPPRESSOR , respectively. While precursor cells of a leaf vein lacking SHR usually follow the geometry rule of dividing along the division plane with the minimum surface area, SHR overrides this rule and forces cells to divide nonpericlinally. Together, these results imply that these bacterially derived GRAS transcription factors were involved in the establishment of the genetic regulatory networks modulating cell division orientation in the common ancestor of land plants and were later adapted to function in flowering plant and moss lineages for their specific body organizations.