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Anna Satake,1 Wataru Kobayashi,1 Yoshihiro Tamura,1 Toshiaki Oyama,1 Haruka Fukuta,1 Akinari Inui,2 Kahori Sawada,2 Kazunari Ihara,2 Takao Noguchi,1 Koichi Murashita,3 Shigeyuki Nakaji2 1Department of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan; 2Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan; 3COI Research Initiatives Organization, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanCorrespondence: Anna SatakeDepartment of Oral and Maxillofacial Surgery, Hirosaki University Graduate School of Medicine, 53 Honcho, Hirosaki-shi, Aomori, JapanTel +81 172 39 5127Fax +81 17 239 5128Email anna12@hirosaki-u.ac.jpPurpose: Oral frailty or the loss of oral functionality can be a symptomatic precursor of overall frailty. Previous studies have suggested that decreased tongue pressure causes a decline in ingesting and swallowing function and poor nutrition. This study investigated what factor(s) contribute to tongue pressure, thereby leading to frailty.Patients and methods: For the purposes of the present study, 467 residents of Hirosaki city in northern Japan aged≥60 years who completed a questionnaire about frailty and underwent an intraoral assessment, which included number of teeth, presence or absence of periodontitis, tongue pressure, and oral diadochokinesis (ODK) were recruited.Results: Of the 467 participants with complete data sets, frailty was identified in 13 (7.5%) of 173 males and in 34 (11.6%) of 294 females. Significantly fewer teeth, lower tongue pressure, and a reduced diadochokinetic syllable rate were more prevalent among frail than among healthy residents. Multivariable logistic regression analysis revealed that age, body mass index, number of teeth, and tongue pressure significantly contributed to frailty, whereas ODK did not. Multiple regression analysis showed that tongue pressure was positively associated with muscle index and number of teeth.Conclusion: The results of the present study suggest that fewer teeth and lower tongue pressure, but not ODK function, are risk factors for developing overall frailty among older residents.Keywords: aging, low nutrition, number of teeth, oral diadochokinesis

Akinari Inui,1 Ippei Takahashi,2 Sizuka Kurauchi,2 Yuki Soma,2 Toshiaki Oyama,1 Yoshihiro Tamura,1 Takao Noguchi,1 Kouichi Murashita,3 Shigeyuki Nakaji,2 Wataru Kobayashi1 1Department of Oral and Maxillofacial Surgery, 2Department of Social Medicine, 3COI Research Initiatives Organization, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori Prefecture, Japan Purpose: Prevention, early detection and effective rehabilitation of dysphagia are important issues to be considered in an aging society. Previous studies have shown conflicting findings regarding the association between dysphagia and its potential risk factors, including age, malnutrition, oral conditions, lifestyle and medical history. Herein, we assessed the prevalence and association of dysphagia with potential risk factors in 50- to 79-year-old adults dwelling in a community in Japan. Patients and methods: In this study, there were 532 participants (185 males and 347 females). Participants who responded positively to the question “Do you sometimes choke on drinks/food such as tea and soup?” or those who presented with abnormal repetitive saliva swallowing test findings were diagnosed with dysphagia. The data collected from these participants included the following: number of teeth, occurrence of oral dryness, age, body mass index, serum albumin concentration, smoking, drinking and exercise habits, presence of diseases, such as diabetes mellitus and hypertension, and questions from the Mini–Mental State Examination. Results: Dysphagia was observed in 33 males (17.8%) and 76 females (21.9%). To explore the effect of the potential risk factors on the prevalence of dysphagia, a model was built by multivariate logistic regression analysis. Using the forced entry method, oral dryness (odds ratio [OR] =3.683 and P=0.003 in males; OR =1.797 and P=0.032 in females) and the number of teeth (OR =0.946 and P=0.038 in males) were found to be significantly related to dysphagia. Conclusion: This cross-sectional study demonstrated associations between oral conditions and dysphagia. Factors such as oral dryness and number of teeth may contribute to dysphagia more so than aging, lifestyle and comorbidity in community-dwelling adults over the age of 50. Keywords: oral dryness, number of teeth, swallow, nutrition, lifestyle

Purpose: This study aimed to clarify the relationship between the oral environment and psychological factors as predictor variables of sleep quality, in addition to inferring the relevant mechanisms of sleep and temporomandibular disorders (TMDs) by analyzing the relationship between TMDs and stress., Methods: This cross-sectional study analyzed data from 1,032 participants, comprising 420 men and 612 women, from the 2017 Iwaki Health Promotion Project using multiple regression analysis. The primary endpoints were the scores of each item in the Pittsburgh Sleep Quality Index (PSQI) and its sum. Predictor variables included the number of teeth; TMDs; stress, assessed using the World Health Organization-5 (WHO-5); sleep bruxism; and oral health-related quality of life, assessed using the oral health impact profile-14 (OHIP14). The confounding factors included age, body mass index, and alcohol intake., Results: Multiple regression analysis revealed that TMDs (β value = 0.293, p = 0.034) and stress (β value = 1.3, p < 0.001) were significantly correlated with the PSQI total score. In addition, TMDs were significantly correlated with stress (β value = 0.076, p = 0.007)., Conclusion: The significant relationship between sleep and TMDs suggests that mental stress contributes to the development sleep disorders and consequently is associated with the development of TMD symptoms., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethics approval and consent to participate This study was approved by the Ethics Committee of Hirosaki University. (Approval No. 2021-030). Written informed consent was obtained from all the participants. Presentation at a conference No., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The association between visceral fat area (VFA) and locomotive syndrome (LS) has been extensively studied in the older population; however, the association between VFA and early-stage LS (stage 1 [LS1]) remains unclear. In this cross-sectional study, we investigated this association across different age groups. The study involved 1,236 (524 male and 712 female) participants (aged 20-85 years). Multiple regression analysis adjusted for sex, body mass index, skeletal muscle mass index, T-score, exercise habits, smoking status, and alcohol consumption revealed a significant association between LS1 and VFA across all VFA quartiles. The adjusted odds ratio OR for quartiles 2, 3, and 4 was 1.84, 2.68, and 4.12, respectively. The association between LS1 and VFA across the age groups-high VFA (> 73 cm 2 ) and non-older (< 65 years) (OR, 1.87; 95% CI, 1.28-2.72; p = 0.001), low VFA (≤ 73 cm 2 ) and older (≥ 65 years) (OR, 3.16; 95% CI, 1.94-5.14; p < 0.001), and high VFA and older groups (OR, 6.43; 95% CI, 3.98-10.4; p < 0.001)-was significantly stronger than that in the low VFA and non-older group. In summary, our findings suggest that managing VFA through diet and exercise is crucial for preventing LS1 across all age groups., (© 2024. The Author(s).)

Objectives: This study examined the impact of the Center of Healthy Aging Program (CHAP) on the cognitive function and economic burden associated with dementia., Methods: This observational study utilised Iwaki cohort data. We included participants with mini-mental state examination (MMSE) scores and categorised them into pre- and post-CHAP groups based on their year of entry into the cohort (before 2013 or after) (index year). We defined participants with suspected severe cognitive impairment and suspected mild cognitive impairment using their MMSE scores, with their incidence being the first observation meeting these definitions during the follow-up period. We compared the incidence rates between the pre- and post-CHAP groups using Cox proportional hazard analysis. Medical and caregiving costs were estimated based on the projected number of residents in Iwaki area with suspected mild cognitive impairment and sSCI during hypothetical 10 years of the CHAP implemented or not and compared., Results: Of the 2,569 participants, 1716 and 853 were included in the pre- and post-CHAP groups, respectively. The incidence rate of suspected mild cognitive impairment was significantly lower in the post-CHAP group even after adjusted known factors associated with cognitive disorders. No cases of suspected severe cognitive impairment occurred in the post-CHAP group during the follow-up period. Estimated costs of JPY 1,628,450 (USD 11562.00 or EUR 10259.24, JPY 100  =  USD 0.71 or EUR 0.63) and JPY 789,560 (USD 5605.88 or EUR 4974.23) per person per year were projected after 10 years with and without the CHAP, respectively., Conclusions: We demonstrated a reduction in the incidence rate of suspected mild cognitive impairment among residents who participated in the CHAP and a decrease in the medical and caregiving costs associated with suspected severe cognitive impairment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS was an employee of Medilead, Inc. and serves as a director of Healthcare Consulting, Inc. KK holds the position of Executive Vice President of Integrated Clinical Care Informatics, Inc. AI received grants from Abbott Japan Inc., Abbvie G.K., Becton, Dickinson and Company, Creative-Ceuticals Inc., Eli Lilly Japan K.K., Gilead Sciences K.K., Intuitive Surgical G.K., Milliman Inc., Pfizer Inc., Sanofi Pasteur Inc., and Terumo Corporation, and personal fees from Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., CSL Behring Japan Inc., FUJIFILM Corporation, Sanofi K.K., and Takeda Pharmaceutical Co., Ltd. outside the submitted work., (Copyright: © 2024 Shoji 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: 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: This study evaluates cost reduction in participants of a health awareness program (the Center of Healthy Aging Program, CHAP) in a Japanese rural area, characterized by an annual check-up and personalized interview on health issues and related risks immediately after the check-up., Methods: This is a cross-sectional study using medical and caregiving costs and Japan-specific health check-up results in Hirosaki residents stored by the local government, which were individually-based linked to the CHAP information collected by Hirosaki University. This is the first study that used anonymized data with individually-based linkages to both a research institute and a local government in Japan under a strict limitation regarding linking to third-party data. We included residents who had been continuously enrolled for > 6 months as of 1 July 2015. We compared 5-year all-cause costs between three groups (with CHAP, with Japan-specific health check-up, and no check-up) using a multivariate negative binomial regression model considering risk factors including lifestyle habits and an inverse probability weight to adjust for baseline characteristics: age, sex, Charlson comorbidity index, baseline care level, and risk score of coronary heart diseases., Results: A total of 384, 9805, and 32,630 residents aged 40-74 years were included for the CHAP, Japan-specific health check-up, and no check-up groups, respectively. The Japan-specific health check-up group showed older and higher Charlson comorbidity index than the others. After inverse probability weight adjusting, the amount of all-cause medical costs was significantly lower only in the CHAP group. Faster walking speed and exercise habits were independently associated with lower all-cause medical and caregiving costs., Conclusions: We demonstrated a 5-year all-cause cost reduction in residents who participated in the CHAP and also suggested the effect of exercise habits in Hirosaki, which indicated the significance of individually-based data linkages to external third-party data for all local governments to improve the health condition of residents., (© 2024. The Author(s).)

Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera's regression coefficients ( Alistipes , Blautia , Coprococcus , Dorea , Faecalibacterium , Holdemania , Lactobacillus , Mitsuokella , and Oscillibacter ) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, Alistipes , Blautia , Coprococcus , Dorea , Faecalibacterium , and Oscillibacter were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process.

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: Several studies have reported that the coronavirus disease (COVID-19) pandemic has increased sedentary behaviour and obesity; however, these analyses used self-reported data, and the association between sedentary behaviour and visceral fat and adipocytokines during the COVID-19 pandemic remains unclear. We aimed to investigate the association of the COVID-19 pandemic with objectively measured sedentary behaviour and these obesity-related factors., Methods: Longitudinal analysis was conducted on 257 Japanese participants who underwent health check-ups in 2018 before and in 2020 during the COVID-19 pandemic. For both time points, sedentary behaviour was measured using an accelerometer for at least 7 days, visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis, and blood adiponectin level was measured using latex agglutination turbidimetric immunoassay. Multiple linear regression was performed to determine the association between sedentary behaviour and these outcomes., Results: Compared with data in 2018, sedentary behaviour and VFA were significantly increased (P < 0.001, P = 0.006) whereas adiponectin level was significantly decreased (P < 0.001) in 2020. Increased sedentary behaviour was significantly associated with an increase in VFA (β = 3.85, 95% CI 1.22-6.49, P = 0.004) and a decrease in adiponectin level (β = -0.04, 95% CI -0.06 to -0.01, P = 0.005). However, the association of sedentary behaviour with adiponectin level was not significant after considering the effects of VFA., Conclusions: The COVID-19 pandemic was associated with objectively measured sedentary behaviour and obesity-related factors in Japanese adults. Additionally, an increase in sedentary behaviour was associated with an increase in VFA, whereas the association of sedentary behaviour with adiponectin was partly mediated by VFA. These results suggest that avoiding increasing sedentary time is important to prevent visceral adiposity thereby ameliorating adiponectin, especially during behavioural limitations such as the COVID-19 pandemic., (© 2023. The Author(s).)

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.

Affordable and accessible behaviour-based interventions that do not overwhelm or demoralise overweight/obese individuals are needed. Combining clothing with behaviour change techniques might be an option. This is because clothing is a social norm, and clothing and motivation for weight loss are associated with the common desire to look better. Therefore, we conducted a single-blind randomised controlled trial to examine the effect of an intervention that combined behaviour change techniques, including simplified goal setting and self-monitoring, with a body compression corrective garment (BCCG), which exerts continuous but minimal tactile pressure on the hips and abdomen. We enrolled healthy community-dwelling adults with a body mass index ≥ 25 kg/m 2 and assigned 35 and 34 participants to the intervention and control groups, respectively. The reduction in body weight was 1.3 kg more in the intervention group than in the control group after the 12-week intervention period ( p < 0.05, repeated-measures mixed model). In addition, eating behaviour and body appreciation showed significant improvement in the intervention group compared with the control group. Our newly developed intervention improved eating behaviour and body appreciation and reduced the body weight of overweight/obese participants. Wearing a BCCG seems to facilitate behavioural changes and lead to weight loss.

Background: Since dementia is preventable with early interventions, biomarkers that assist in diagnosing early stages of dementia, such as mild cognitive impairment (MCI), are urgently needed., Methods: Multiomics analysis of amnestic MCI (aMCI) peripheral blood (n = 25) was performed covering the transcriptome, microRNA, proteome, and metabolome. Validation analysis for microRNAs was conducted in an independent cohort (n = 12). Artificial intelligence was used to identify the most important features for predicting aMCI., Findings: We found that hsa-miR-4455 is the best biomarker in all omics analyses. The diagnostic index taking a ratio of hsa-miR-4455 to hsa-let-7b-3p predicted aMCI patients against healthy subjects with 97% overall accuracy. An integrated review of multiomics data suggested that a subset of T cells and the GCN (general control nonderepressible) pathway are associated with aMCI., Interpretation: The multiomics approach has enabled aMCI biomarkers with high specificity and illuminated the accompanying changes in peripheral blood. Future large-scale studies are necessary to validate candidate biomarkers for clinical use., 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 © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

To promote health awareness and improve life expectancy in Hirosaki, a Japanese rural area, the Center of Healthy Aging Program (CHAP) was founded in 2013. The most important characteristic of CHAP is a personalized interview just after the checkup to discuss individual results. We evaluated the clinical and economic effects of CHAP by analyzing the cohort data of voluntary participants from annual health checkups since 2005 in the Iwaki district of Hirosaki. We calculated 10-year incidence risk scores for coronary heart diseases (CHDs) and stroke, and compared the risk-score trend before and after the start of CHAP by adjusting other risk factors using multivariate generalized linear regression analyses. We also predicted the 10-year incidences of CHDs and stroke based on the risk scores, for future scenarios of the two conditions, with and without CHAP, and compared them to their treatment costs between scenarios. The number of participants ranged between 808 and 1,167, from 2008 to 2016. The mean age (55 years) and proportion of women (60%) did not significantly change throughout the period. After adjusting for sex, age, outside temperature on the checkup date, the preparation effect of CHAP in 2012, and risk scores in the previous year, the annual increases in risk scores of CHDs and stroke were significant even after CHAP (+0.413, p <0.001; +0.169, p <0.001, respectively), but slightly less compared to before CHAP (+2.638, p <0.001; +1.155, p <0.001, respectively). Assuming the trend continued until 2021, the 10-year incidences of CHDs and stroke have decreases by 22,486 and 9,603, respectively, and treatment costs decreased by JPY 21,973 and 16,056 million, respectively. CHAP contributes to a significant decrease in the incidences of CHDs and stroke, and reduces economic burden on the local government., Competing Interests: The potential competing interests of authors (if any) are otherwise summarized in the following sentences. AS is employee of Medilead Inc. KK is COE of Integrated Clinical Care Informatics, Inc. AI has received grants from Abbott Japan Inc., Abbvie G.K., Becton, Dickinson and Company, Creative-Ceuticals Inc., Eli Lilly Japan K.K., Gilead Sciences K.K., Intuitive Surgical G.K., Milliman Inc., Pfizer Inc., Sanofi Pasteur Inc., and Terumo Corporation, and personal fees from Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., CSL Behring Japan Inc., FUJIFILM Corporation, Sanofi K.K., and Takeda Pharmaceutical Co., Ltd. outside the submitted work. These do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Shoji 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.)

To reveal direct effects of various protein sources on digestive physiology of red seabream, Pagrus major (38.5 ± 0.4 g), six different protein sources of fishmeal (FM), soybean meal (SBM), corn gluten meal (CGM), soy protein concentrate (SPC), poultry by-product meal (PBM), and poultry-feather meal (PFM) were orally administered to fish (2 mg protein/g body weight) and sampled at 1.5 h and 3 h after administration. Gallbladder weight of fish administered FM, PBM, and PFM decreased after administration (p < 0.0001), while no difference was observed in the other ingredients compared to a non-protein sham control group, indicating that animal protein sources could more strongly stimulate bile secretion than plant protein sources in red seabream. Trypsin and chymotrypsin activity in the intestinal content markedly increased by the FM, SBM, and PFM administration (p < 0.0001). Lipase and amylase activity was also increased by FM and SBM but also by CGM for lipase and by PBM and PFM for amylase (p < 0.0001). These indicate that stimulation effect of the secretion of digestive enzymes is largely different among the protein sources. This might be due to the absorptive capacity of the protein source since intestinal absorption parameter genes (anpep, cpa, ggt1, and atp1a2) also increased by the FM, SBM, PBM or PFM (p < 0.05). In addition to the secretion levels of bile and digestive enzymes, gene expression levels of bile related genes (cyp7a1, cyp8b1, and shp) and digestion-regulating genes (casr and cck) were increased by the FM, SBM, PFM, and/or PBM administration, suggesting that animal proteins and SBM could be potent digestive stimulants compared to CGM and SPC. This study first revealed that single protein sources directly influence digestive enzyme secretion and bile secretion in fish. Information about the direct effect of each single source on digestive physiology could help to design feed formulation with less fishmeal., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The correlation between diabetes-related biomarkers and quality of life (QOL) remains unclear. In this cross-sectional study, we investigated the correlation between diabetes-related biomarkers and QOL in a general Japanese population who underwent health checkups as a part of the Iwaki Health Promotion Project. Male and female participants aged ≥ 20 years from Iwaki District, Hirosaki City, Aomori Prefecture who participated in the 2019 medical evaluation were recruited. QOL was evaluated using the Short Form Health Survey 36 (SF-36). Fasting blood glucose, homeostatic model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), glycoalbumin, and plasma pentosidine were also evaluated as diabetes-related markers. Of the 1065 recruited participants, 1053 completed the clinical and QOL evaluations. Multivariate regression analysis revealed that upregulated diabetes-related markers levels were correlated with decreased SF-36 scores. Blood glucose, HOMA-IR, HbA1c, glycoalbumin, and plasma pentosidine levels were correlated with general health. Moreover, plasma pentosidine levels were correlated with role physical, social functioning, and role emotional in addition to general health. These results indicated that the levels of diabetes-related biomarkers, particularly the levels of plasma pentosidine, a glycation marker, were associated with QOL in our cohort.

Background: Several studies have reported that obesity is associated with influenza infection; however, the role of visceral fat remains unclear. The aim of this study was to investigate the association between visceral fat and influenza infection in community-dwelling Japanese adults., Methods: A cross-sectional study was performed using data from an annual community-based health check-up conducted from May to June in 2019. In total, 1,040 Japanese adults aged 20-89 years were enrolled in this study. Influenza infection status was determined by participants' responses to a self-administered questionnaire. The visceral fat area (VFA) was measured using a bioimpedance-type visceral fat meter. Participants were classified into four groups using the following cut-off points: VFA < 100 cm2 was set as the reference category according to the Japanese criteria, 100 ≤ VFA < 150 cm2, 150 ≤ VFA < 200 cm2, and 200 cm2 ≤ VFA. Logistic regression models were used to assess the association between VFA and influenza infection., Results: In total, 119 participants had influenza infections in the past year. In the multivariate adjusted model, a higher VFA was significantly associated with increased influenza infection; the adjusted odds ratio for 200 cm2 ≤ VFA was 5.03 [95% confidence interval (CI): 1.07-23.6], that for 150 ≤ VFA < 200 cm2 was 1.97 (95% CI: 0.71-5.45), and that for 100 ≤ VFA < 150 cm2 was 1.62 (95% CI: 0.84-3.12), compared with that for VFA < 100 cm2 (p for trend = 0.049). These findings were confirmed in the same cohort the following year., Conclusions: Our results suggest that visceral fat accumulation is associated with influenza infection. Large-scale prospective studies using diagnostic information for influenza infection are required to confirm this association., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: authors K.K., N.O., T.Y., K.M., and Y.K. are employees of Kao Corporation (Tokyo, Japan). All other authors declare no potential competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Amylase genes reside in a structurally complex locus, and their copy numbers vary greatly, and several studies have reported their association with obesity. The mechanism of this effect was partially explained by changes in the oral and gut microbiome compositions; however, a detailed mechanism has been unclarified. In this study, we showed their association with diabetes in addition to obesity, and further discovered a plausible mechanism of this association based on the function of commensal bacteria. First, we confirmed that the amylase copy number in the population tends to be larger than that reported in other studies and that there is a positive association between obesity and diabetes (p = 1.89E-2 and 8.63E-3). Second, we identified that relative abundance of some genus level microbiome, Capnocytophaga, Dialister, and previously reported bacteria, were significantly associated with amylase copy numbers. Finally, through functional gene-set analysis using shotgun sequencing, we observed that the abundance of genes in the Acarbose pathway in the gut microbiome was significantly decreased with an increase in the amylase copy number (p-value = 5.80E-4). Our findings can partly explain the mechanism underlying obesity and diabetes in populations with high amylase copy numbers., (© 2022. The Author(s).)

The high-affinity/low-capacity system Slc15a2 (PepT2) is responsible for the reuptake of di/tripeptides from the renal proximal tubule, but it also operates in many other tissues and organs. Information regarding PepT2 in teleost fish is limited and, to date, functional data are available from the zebrafish (Danio rerio) only. Here, we report the identification of two slc15a2 genes in the Atlantic salmon (Salmo salar) genome, namely slc15a2a and slc15a2b. The two encoded PepT2 proteins share 87% identity and resemble both structurally and functionally the canonical vertebrate PepT2 system. The mRNA tissue distribution analyses reveal a widespread distribution of slc15a2a transcripts, being more abundant in the brain and gills, while slc15a2b transcripts are mainly expressed in the kidney and the distal part of the gastrointestinal tract. The function of the two transporters was investigated by heterologous expression in Xenopus laevis oocytes and two-electrode voltage-clamp recordings of transport and presteady-state currents. Both PepT2a and PepT2b in the presence of Gly-Gln elicit pH-dependent and Na + independent inward currents. The biophysical and kinetic analysis of the recorded currents defined the transport properties, confirming that the two Atlantic salmon PepT2 proteins behave as high-affinity/low-capacity transporters. The recent structures and the previous kinetic schemes of rat and human PepT2 qualitatively account for the characteristics of the two Atlantic salmon proteins. This study is the first to report on the functional expression of two PepT2-type transporters that operate in the same vertebrate organism as a result of (a) gene duplication process(es). KEY POINTS: Two slc15a2-type genes, slc15a2a and slc15a2b coding for PepT2-type peptide transporters were found in the Atlantic salmon. slc15a2a transcripts, widely distributed in the fish tissues, are abundant in the brain and gills, while slc15a2b transcripts are mainly expressed in the kidney and distal gastrointestinal tract. Amino acids involved in vertebrate Slc15 transport function are conserved in PepT2a and PepT2b proteins. Detailed kinetic analysis indicates that both PepT2a and PepT2b operate as high-affinity transporters. The kinetic schemes and structures proposed for the mammalian models of PepT2 are suitable to explain the function of the two Atlantic salmon transporters., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The association between sedentary behaviour and sleep quality (SQ) remains unclear, partly due to the limited methodology for assessing sedentary time and the influence of obesity. This study aimed to examine the association between objectively measured sedentary time and poor SQ, as well as the association of visceral fat accumulation. This cross-sectional study used health check-up data obtained from 721 Japanese adults. Sedentary time and physical activity were measured using an accelerometer for ≥7 days, with ≥10 measurement hours per day. Poor SQ was determined by a Pittsburgh Sleep Quality Index score of ≥ 6. Visceral fat was measured using the abdominal bioimpedance method. A logistic regression model was used to analyse the association between sedentary time and SQ. We found that higher sedentary time was associated with poorer SQ. This association remained significant after adjustment for several covariates, including visceral fat. Compared with the lowest tertile of sedentary time, the second and highest tertile had a significantly higher OR of poor SQ (Tertile 2: OR = 2.06 [95% CI 1.14,3,73]; Tertile 3: OR = 2.76 [95% CI 1.49, 5.11]). These results suggest that managing sedentary time itself might contribute to improving SQ.

Intestinal microflora has been associated with obesity. While visceral fat is more strongly associated with cardiovascular disorder, a complication linked to obesity, than the body mass index (BMI), the association between intestinal microflora and obesity (as defined in terms of BMI) has been studied widely. However, the link between visceral fat area (VFA) and intestinal microflora has been little studied. In this study, we investigate the association between intestinal microflora and VFA and BMI using a longitudinal study on Japanese subjects with different VFA statuses ( N = 767). Principal component analysis of the changes in intestinal microflora composition over the one-year study period revealed the different associations between intestinal microflora and VFA and BMI. As determined by 16S rRNA amplicon sequencing, changes in the abundance ratio of two microbial genera- Blautia and Flavonifractor -were significantly associated with VFA changes and changes in the abundance ratio of four different microbial genera were significantly associated with BMI changes, suggesting that the associated intestinal microbes are different. Furthermore, as determined by metagenomic shotgun sequences, changes in the abundance ratios of two Blautia species- Blautia &nbsp; hansenii and Blautia &nbsp; producta -were significantly and negatively associated with VFA changes. Our findings might be used to develop a new treatment for visceral fat.

Although the Asian population exhibits excessive sedentary behaviour and has a high susceptibility to metabolic syndrome (MetS), the nature of these associations remains unclear. This study aimed to investigate the association of sedentary time with cardiometabolic health and examine the association of reallocating sedentary time to light physical activity (LPA) or moderate-vigorous physical activity (MVPA) on cardiometabolic health in Japanese adults. A cross-sectional study was performed using data obtained from 758 Japanese adults. We assessed sedentary time, LPA, and MVPA using an accelerometer. Linear and logistic regression models were used to analyse the association between sedentary time and cardiometabolic risk factors. An isotemporal substitution model was used to estimate the theoretical influence of reallocating sedentary time to LPA or MVPA. A longer sedentary time was associated with worse cardiometabolic health, including MetS. Reallocating 30 min of sedentary time to LPA was significantly associated with lower body mass index, visceral fat, insulin resistance, triglyceride, and MetS levels and increased muscle mass and HDL-C (all P < 0.05). Reallocating 30 min of sedentary time to MVPA was strongly associated with the aforementioned factors. These results demonstrate the potential beneficial effects of reallocating sedentary time to LPA and MVPA on cardiometabolic health of Asians., (© 2022. The Author(s).)

Hypertension (HT) is an important risk factor for mortality and morbidity. Previous studies showed that cadmium (Cd) was associated with increased blood pressures and the prevalence of HT. This study hypothesized that Cd, regardless of its level, may increase blood pressures/HT. The objective of this study was to examine the associations between a low level of serum Cd concentration and blood pressures/HT among a general population in the Iwaki area, Japan. This was a cross-sectional study, conducted in the Aomori prefecture with 1144 volunteers aged over 19 years old, who were participants of the Iwaki health check-up in 2014. The study assessed questionnaire survey, body composition, and serum Cd concentrations. Median serum Cd concentration was 0.06 ng/mL (interquartile range 0.05-0.08 ng/mL) among our study population. Compared to the lowest quintile of serum Cd concentration group, the highest quintile of serum Cd concentration group had 4.9 mmHg higher systolic blood pressure (SBP) (95% confidence interval [CI] 1.53-8.31, p < 0.01) and 2.4 mmHg higher diastolic blood pressure (DBP) (95% CI 0.36-4.34, p < 0.05), compared to the lowest quintile group. Similarly, the highest quintile of serum Cd concentration group had 1.7 times higher prevalence of HT (95% CI 1.10-2.51, p < 0.05) than the lowest quintile group. This study identified that higher serum Cd concentration was significantly, positively, associated with SBP and DBP and HT prevalence. This study provided evidence for the associations between environmental exposure to Cd and blood pressures/HT which should be considered for future preventive measures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Telomere (TL) is a biomarker of biological aging, and its shortening is associated with major risk factors for cardiovascular diseases (CVD). This study aimed to identify whether TL is associated with arterial stiffness as reflected by brachial-ankle pulse wave velocity (baPWV). This population-based cross-sectional study involved 1065 individuals in the Iwaki area, Japan. Total TL length and TL G-tail length were measured by hybridization protection assay. The baPWV was measured on the right and left sides using a non-invasive vascular screening device. The associations between TL and baPWV were assessed by multivariate linear regression. Compared with the shortest total TL tertile, the longest total TL group showed a significant decrease in baPWV (lowest vs. highest tertile: adjusted beta: -41.24, 95% confidence interval (CI): -76.81, -5.68). The mean baPWV decreased with a longer TL (TL G-tail length: p trend < 0.001, total TL: p trend < 0.001). TL G-tail and total TL lengths were inversely associated with baPWV, implicating TL shortening in the development of CVD. This study provides evidence of the factors influencing CVD risks at a very early stage when individuals can still take necessary precautions before CVD gives rise to a symptomatic health outcome.

In mammals, knockout of LEPR results in a hyperphagic, morbid obese, and diabetic phenotype, which supports that leptin plays an important role in the control of appetite and energy metabolism, and that its receptor, LEPR, mediates these effects. To date, little is known about the role(s) of lepr in teleost physiology. We investigated a zebrafish (Danio rerio) homozygous lepr knockout (lepr -/- ) line generated by CRISPR/Cas9 in comparison to its wt counterpart with respect to nutrient acquisition, energy allocation, and metabolism. The metabolic characterization included oxygen consumption rate and morphometric parameters (yolk sac area, standard length, wet weight, and condition factor) as proxies for use and allocation of energy in developing (embryos, larvae, and juveniles) zebrafish and showed no particular differences between the two lines, in agreement with previous studies. One exception was found in oxygen consumption at 72 hpf, when zebrafish switch from embryonic to early larval stages and food-seeking behavior could be observed. In this case, the metabolic rate was significantly lower in lepr -/- than in wt. Both phenotypes showed similar responses, with respect to metabolic rate, to acute alterations (22 and 34 °C) in water temperature (measured in terms of Q 10 and activation energy) compared to the standard (28 °C) rearing conditions. To assess lepr involvement in signaling the processing and handling of incoming nutrients when an exogenous meal is digested and absorbed, we conducted an in vivo analysis in lepr -/- and wt early (8 days post-fertilization) zebrafish larvae. The larvae were administered a bolus of protein hydrolysate (0%, 1%, 5%, and 15% lactalbumin) directly into the digestive tract lumen, and changes in the mRNA expression profile before and after (1 and 3 h) administration were quantified. The analysis showed transcriptional differences in the expressions of genes involved in the control of appetite and energy metabolism (cart, npy, agrp, and mc4r), sensing (casr, t1r1, t1r3, t1r2-1, t1r2-2, pept1a, and pept1b), and digestion (cck, pyy, try, ct, and amy), with more pronounced effects observed in the orexigenic than in the anorexigenic pathways, suggesting a role of lepr in their regulations. Differences in the mRNA levels of these genes in lepr -/- vs. wt larvae were also observed. Altogether, our analyses suggest an influence of lepr on physiological processes involved in nutrient acquisition, mainly control of food intake and digestion, during early development, whereas metabolism, energy allocation, and growth seem to be only slightly influenced., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The relationship between chronic kidney disease (CKD) and the gut microbiome, which interact through chronic inflammation, uraemic toxin production and immune response regulation, has gained interest in the development of CKD therapies. However, reports using shotgun metagenomic analysis of the gut microbiome are scarce, especially for early CKD. Here we characterized gut microbiome differences between non-CKD participants and ones with early CKD using metagenomic sequencing., Methods: In total, 74 non-CKD participants and 37 participants with early CKD were included based on propensity score matching, controlling for various factors including dietary intake. Stool samples were collected from participants and subjected to shotgun sequencing. Bacterial and pathway abundances were profiled at the species level with MetaPhlAn2 and HUMAnN2, respectively, and overall microbiome differences were determined using Bray-Curtis dissimilarities. Diabetic and non-diabetic populations were analysed separately., Results: For diabetic and non-diabetic participants, the mean estimated glomerular filtration rates of the CKD group were 53.71 [standard deviation (SD) 3.87] and 53.72 (SD 4.44), whereas those of the non-CKD group were 72.63 (SD 7.72) and 76.10 (SD 9.84), respectively. Alpha and beta diversities were not significantly different between groups. Based on taxonomic analysis, butyrate-producing species Roseburia inulinivorans, Ruminococcus torques and Ruminococcus lactaris were more abundant in the non-CKD group, whereas Bacteroides caccae and Bacteroides coprocora were more abundant in the non-diabetic CKD group., Conclusions: Although gut microbiome changes in individuals with early CKD were subtle, the results suggest that changes related to producing short-chain fatty acids can already be observed in early CKD., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)