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Background Walkable neighbourhoods promote physical activity and prevent obesity, but there is limited evidence to inform urban planning strategies for public health within the context of rural Japan. This study describes associations between neighbourhood walkability and obesity in Toyama, a regional municipality in Japan. Methods A cross-sectional analysis of the Toyama Prefecture National Health Insurance data (n  = 3454) in 2016 using Analysis of Covariance (ANCOVA) and binary logistic regression. Walk Score® was used to estimate neighbourhood walkability. Results Residents from highly walkable neighbourhoods generally had lower mean body mass index (BMI), but significant associations between neighbourhood walkability and BMI and prevalence of obesity were only observed in women (adjusted OR: 0.46, 95% CI: 0.26–0.80). Men below 65 years old had higher obesity prevalence (adjusted OR: 1.76, 95% CI: 1.34–2.30). Daily alcohol consumption was associated with lower odds of being obese among men (adjusted OR: 0.72, 95% CI: 0.55–0.95). Hypertension, diabetes mellitus and dyslipidaemia were associated with higher obesity prevalence among residents, regardless of gender. Conclusions Walkable environment may improve health outcomes for rural communities in Japan. Further studies are required to create equitable and inclusive living spaces for men and women to access healthier lifestyle choices. [ABSTRACT FROM AUTHOR]

The aim of the present study was to clarify the structural relationship between health-related habits and psychosocial factors during adolescence/early adulthood. An anonymous, self-administered questionnaire was provided to 1141 third- and fourth-year students at eight academic departments from six universities in regional Japanese cities. Surveys included items addressing participants' demographic characteristics, psychosocial factors (individual-level social capital, self-efficacy, mental health (from health-related quality of life SF-36v2), and sense of coherence (SOC)), and health-related habits. A multiple indicator analysis based on structural equation modeling was conducted to examine the structural relationship between health-related habits and these factors. Valid responses were obtained from 952 participants. The final model demonstrated a high level of goodness of fit. While the path from SOC to health-related habits was significant, those from self-efficacy to health-related habits and from mental health to health-related habits were not significant. The path coefficient from SOC to health-related habits was greater than the path coefficient from background characteristics. In the multiple population comparison that considered gender, a nearly identical model was supported for men and women. Psychosocial factors related to health-related habits were social capital, self-efficacy, mental health, and SOC. Furthermore, it was suggested that SOC functions as an intervening factor for maintaining a healthy lifestyle. It was observed that individual psychosocial factors influence health-related habits more than their background characteristics. Findings highlight that supporting the building of social relationships and social environments is essential to promote a healthy lifestyle among university students. [ABSTRACT FROM AUTHOR]

Objective. B cells play an important role in the pathogenesis of autoimmune diseases. The role of Bruton's tyrosine kinase (Btk) in cytokine-induced human B cell differentiation and class-switch recombination remains incompletely defined. This study analysed the effect of Btk on human activated B cells. Methods. Purified B cells from healthy subjects were stimulated with B cell receptor (BCR) and other stimuli with or without a Btk inhibitor and gene expression was measured. The B cell line BJAB was used to assess Btk-associated signalling cascades. Phosphorylated Btk (p-Btk) in peripheral blood B cells obtained from 10 healthy subjects and 41 patients with RA was measured by flow cytometry and compared with patient backgrounds. Results. IL-21 signalling, in concert with BCR, CD40 and BAFF signals, led to robust expression of differentiation- and class-switch DNA recombination-related genes and IgG production in human B cells, all of which were significantly suppressed by the Btk inhibitor. Although phosphorylation of STAT1 and STAT3 was induced by co-stimulation with IL-21, BCR and CD40, STAT1 phosphorylation in the nucleus, but not in the cytoplasm, was exclusively impaired by Btk blockade. High levels of p-Btk were noted in B cells of RA patients compared with controls and they correlated significantly with titres of RF among RF-positive patients. Conclusion. The findings elucidate a model in which Btk not only plays a fundamental role in the regulation of BCR signalling, but may also mediate crosstalk with cytokine signalling pathways through regulation of IL-21-induced phosphorylation of STAT1 in the nuclei of human B cells. Btk appears to have pathological relevance in RA. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effectiveness of brief intervention (BI) conducted in the workplace for heavy drinkers. Methods: A randomized controlled trial was conducted at six companies in Japan. Participants were heavy drinkers who met the inclusion criteria and were randomized into three groups: the BI group, BI with diary group and a control group. Outcomes (total drinks, binge drinking episodes and alcohol-free days) were evaluated at 3 and 12 months. Results: The 304 participants recruited were allocated to the three groups and 277 participated in all follow-up evaluations. Dropout rates in the respective groups were 7.0, 14.9 and 5.5%. Some improvements were observed in all the groups. In particular, alcohol-free days in the BI group were significantly increased by 93.0% at 12 months. Total drinks at 12 months were reduced by 41 g per week in the BI group compared with the control group, although the intergroup difference was not significant. Conclusion: BI in the workplace is effective for increasing the number of alcohol-free days. However, the effectiveness on decreasing alcohol consumption was unclear, which could be explained by alcohol screening itself causing a reduction in drinking. [ABSTRACT FROM PUBLISHER]

Objective. The mechanisms of ectopic calcification in inflammatory diseases are poorly understood. We investigated the effects of inflammatory cytokines on the mechanisms of calcification in human adipose tissue-derived mesenchymal stem cells (hADSCs).Methods. The effects of inflammatory cytokines were evaluated using hADSCs cultured in osteoblast induction medium. mRNA expression was measured by real-time PCR and protein levels were measured by western blotting. Cell mineralization was evaluated by Alizarin Red S staining.Results. In hADSCs, administration of IL-6/soluble IL-6 receptor (sIL-6R), TNF or IL-1β accelerated calcification through enhanced expression of an osteoblast differentiation marker, runt-related transcription factor 2 (RUNX2). IL-6/sIL-6R had the greatest effect. The transcription of mRNA for receptor tyrosine kinase-like orphan receptor 2 (ROR2), involved in the non-canonical wingless-type (WNT) MMTV integration site pathway, was increased, while β-catenin expression, an essential factor in the canonical WNT signalling pathway for osteoblast differentiation, did not change. Suppression of signal transducer and activator of transcription 3 (STAT3), but not STAT1, by small interfering RNA (siRNA) exerted a strong inhibitory effect on RUNX2 and ROR2 expression, and inhibited accelerated calcification.Conclusion. IL-6/sIL-6R stimulation accelerated the ROR2/WNT5A pathway in hADSCs in a STAT3-dependent manner, resulting in augmented calcification. These results suggest that the mechanisms of ectopic calcification accelerated by IL-6 in hADSCs may be involved in chronic inflammatory tissues and that IL-6 inhibitors may be beneficial in the treatment of ectopic calcification in inflammatory diseases. [ABSTRACT FROM PUBLISHER]

Objective. The aim of this study was to characterize arthropathies of the hands associated with anti-aminoacyl tRNA synthetase (ARS) autoantibodies.Methods. Fifty-six patients with anti-ARS antibodies were selected from consecutive patients who visited Keio University Hospital between1983 and 2011, based on their joint symptoms and the availability of hand X-rays. Their clinical characteristics, anti-CCP antibodies, RF, and hand X-ray findings were retrospectively examined.Results. Based on characteristic hand X-ray findings, the anti-ARS-positive patients with joint symptoms could largely be categorized into three groups. The predominant group (64%) was patients with no significant X-ray findings. The remaining patients with destructive changes were classified into two distinct groups. One group had mainly erosions in the PIP and MCP joints and/or ankylosis of the wrists with anti-CCP and RF, which is consistent with the features of RA. The other group showed subluxation of the thumbs and periarticular calcification that was independent of anti-CCP or RF, which is exclusively found in anti-Jo-1-positive patients.Conclusion. Autoantibody profiles, including anti-CCP, RF and individual anti-ARS specificities, are useful in classifying anti-ARS-associated arthropathies of the hands into RA or anti-Jo-1-related disorders. [ABSTRACT FROM PUBLISHER]

Objective. In RA, response to TNF blockers may be associated with a profile of cytokine production unique to each patient. This study sought to predict the response to biologic agents by examining pro-inflammatory cytokine synthesis in stimulated whole blood cultures (WBCs).Methods. We measured the concentration of TNF-α, IL-1β and IL-6 in supernatants of lipopolysaccharide (LPS)-stimulated WBCs obtained from RA patients (n = 41) before anti-TNF therapy (infliximab, 13; etanercept, 26; and adalimumab, 2) and from healthy controls (n = 12). At 24 weeks after biologics, whole bloods were again drawn from 14 of 41 patients. Response was defined by the European League Against Rheumatism response criteria after 24 weeks of therapy.Results. Among 41 patients, 32 were responders (good 14/moderate 18), while 9 were non-responders. All cytokines measured were significantly lower in RA patients than in controls. In RA, IL-1β production was lower in non-responders than in responders [median (interquartile range): 3.5 (1.5–9.4) vs 10.0 (5.1–93.1) pg/ml, P = 0.048]. The area under the curve from a receiver operating characteristic curve analysis for the prediction of response using IL-1β was 0.717 (95% CI 0.520, 0.914). The sensitivity and specificity of IL-1β (cut-off value 4.84 pg/ml) was 78.1 and 77.8%, respectively. All cytokines were significantly higher 6 months later compared with their respective baseline.Conclusion. IL-1β measurement in LPS-stimulated WBC is useful to predict responsiveness to anti-TNF agents. Cytokine production capacities in LPS-stimulated WBCs are up-regulated by biologics. [ABSTRACT FROM PUBLISHER]

Children in early adolescence and their mothers were studied to clarify the association between a child's sense of coherence (SOC) and its mother's SOC, the quality of family relationships as gauged by the mother, and the child's positive life experiences at home. An anonymous self-administered group questionnaire was given to all 1540 students of a high school in Tokyo, and a similar questionnaire was sent by mail to their legal guardians. Responses were received from 1505 students (response rate: 97.7%) and 989 legal guardians (response rate: 64.2%); questionnaires completed by legal guardians who were the mothers of the students were paired with the corresponding child's questionnaire. The SOC scores of mothers and students were calculated, and hierarchical multiple regression analysis was performed with the student's SOC as a dependent variable. Results for boys revealed that a mother's SOC was directly related to the child's SOC, regardless of family relationships and participation in decision-making at home. For girls, a mother's SOC was related to family relationships and was indirectly related to the child's SOC through the child's participation in decision-making at home. Results revealed that for both boys and girls, a mother's SOC had an effect on the child's SOC, and this corroborates the hypothesis of Antonovsky. [ABSTRACT FROM AUTHOR]

Objective. Although findings of nail-fold capillary changes and reduced red blood cell velocity in SSc patients are well established, studies in adult-onset DM patients are scarce. Our objective was to assess the changes and red blood cell velocity in finger nail-fold capillaries using nail-fold video capillaroscopy (NVC) in patients with adult-onset DM.Methods. This study included 50 patients with adult-onset DM and 20 healthy subjects. A semi-quantitative rating scale was used to score capillaroscopy changes. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps.Results. Thirty-seven (74%) patients showed the scleroderma NVC pattern. Patients with the scleroderma pattern exhibited elevated serum creatine kinase levels more frequently and increased visual analogue scale of muscle disease activity. Scores of loss of capillaries were associated with muscle and global disease activity, whereas scores of haemorrhages were associated with skin disease activity. However, NVC findings were not significantly associated with lung involvement. The scores of irregularly enlarged capillaries, haemorrhages and loss of capillaries were reduced after stabilization of disease activity by treatment. The mean red blood cell velocity was not significantly reduced in DM patients compared with healthy controls and was not changed by treatment.Conclusion. Our results suggest that changes in nail-fold capillaries reflect disease activity in DM. Furthermore, the differences found in red blood cell velocity may reflect somewhat distinct microcirculation injuries in DM and SSc. [ABSTRACT FROM PUBLISHER]

Aims: The purpose of this study was to determine whether diabetes affects relationships between alcohol intake and atherosclerotic risk factors. Methods: Age- and alcohol intake-matched groups of Japanese men with and without diabetes (each group: n = 1440) were prepared. Relationships of alcohol intake with atherosclerotic risk factors were compared among four subgroups divided by alcohol intake [non-, light (<22 g/day), moderate (≥22 and <44 g/day) and heavy (≥44 g/day) drinkers]. Results: Both in diabetic and non-diabetic groups, blood pressure was significantly higher in moderate and heavy drinkers than in non-drinkers, triglycerides were significantly higher in heavy drinkers than in non-drinkers, and high-density lipoprotein (HDL) cholesterol was significantly higher in all drinker groups than in non-drinkers. In the diabetic group, body mass index (BMI) was significantly lower (P < 0.01) in moderate and heavy drinkers than in non-drinkers [26.11 ± 0.17 kg/m2 (non-drinkers) vs. 24.83 ± 0.19 kg/m2 (moderate drinkers) vs. 24.97 ± 0.23 kg/m2 (heavy drinkers)], while these differences were not found in the non-diabetic group [23.33 ± 0.13 kg/m2 (non-drinkers) vs. 23.30 ± 0.15 kg/m2 (moderate drinkers) vs. 23.46 ± 0.18 kg/m2 (heavy drinkers)]. Both in the diabetic and non-diabetic groups, low-density lipoprotein (LDL) cholesterol was significantly lower in moderate and heavy drinkers than in non-drinkers. In the non-diabetic group, LDL cholesterol was also significantly lower in light drinkers than in non-drinkers [124.7 ± 1.3 mg/dl (non-drinkers) vs. 114.5 ± 2.4 mg/dl (light drinkers), P < 0.01], while this difference was not found in the diabetic group [123.6 ± 1.4 mg/dl (non-drinkers) vs. 123.1 ± 2.6 mg/dl (light drinkers)]. Conclusion: The positive associations of alcohol intake with blood pressure, triglycerides and HDL cholesterol are similar in men with and without diabetes, while the negative associations of alcohol intake with BMI and LDL cholesterol are stronger and weaker, respectively, in men with diabetes than in men without diabetes. [ABSTRACT FROM AUTHOR]