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Background/Objectives: Animal studies have demonstrated that soy isoflavones exert antidiabetic effects. However, evidence regarding the association between soyfood intake, a unique source of isoflavones, and type 2 diabetes remains inconclusive. This study assessed the relationship between habitual intakes of soyfoods and major isoflavones and risk of type 2 diabetes in Vietnamese adults. Subjects/Methods: A hospital-based case-control study was conducted in Vietnam during 2013–2015. A total of 599 newly diagnosed diabetic cases (age 40–65 years) and 599 hospital-based controls, frequency matched by age and sex, were recruited in Hanoi, capital city of Vietnam. Information on frequency and quantity of soyfood and isoflavone intake, together with demographics, habitual diet and lifestyle characteristics, was obtained from direct interviews using a validated and reliable questionnaire. Unconditional logistic regression analyses were performed to examine the association between soy variables and type 2 diabetes risk. Results: Higher intake of total soyfoods was significantly associated with a lower risk of type 2 diabetes; the adjusted odds ratio (OR) for the highest versus the lowest intake was 0.31 (95% confidence interval (CI): 0.21–0.46; P <0.001). An inverse dose–response relationship of similar magnitude was also observed for total isoflavone intake (OR: 0.35; 95% CI: 0.24 to 0.49; P <0.001). In addition, inverse associations of specific soyfoods (soy milk, tofu and mung bean sprout) and major isoflavones (daidzein, genistein and glycitein) with the type 2 diabetes risk were evident. Conclusions: Soyfood and isoflavone intake was associated with a lower type 2 diabetes risk in Vietnamese adults.

Aims/hypothesis Systemic pro- and anti-inflammatory cytokines are associated with both type 1 and type 2 diabetes, while their role in latent autoimmune diabetes in adults (LADA) is unclear. Therefore, we compared cytokine concentrations in patients with LADA, type 1 or type 2 diabetes and healthy individuals to test the hypothesis that differences of cytokine concentrations between all groups are attributable to diabetes type and BMI. Methods The pro-inflammatory cytokines IL-6 and TNF-α, and the anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and IL-10 were measured in 90 participants with type 1 diabetes, 61 with LADA, 465 with type 2 diabetes and 41 control participants using multiple regression models adjusted for BMI, sex, age, blood pressure and diabetes duration. Results Patients with type 2 diabetes had higher concentrations of systemic IL-1RA, IL-6 and TNF-α cytokines than patients with either LADA or type 1 diabetes ( p  < 0.0001 for all differences). Cytokine concentrations in controls were lower than those in all diabetes types ( p  < 0.04). Increased BMI was positively associated with higher systemic cytokine concentrations in all diabetes types ( p  < 0.0001). Despite the association of cytokines with anthropometric data, differences between diabetes forms persisted also after adjusting analysis for the confounders BMI, age, sex, disease duration and blood pressure ( p  < 0.04). Conclusions/interpretation Although body mass associates positively with pro- and anti-inflammatory cytokine levels, patients with type 2 diabetes have higher cytokine levels independent of the prevailing BMI. LADA and type 1 diabetes could not be distinguished by systemic cytokines.

Cognitive judgement bias (CJB) refers to the interpretation of ambiguous stimuli in a negative (pessimistic) or positive (optimistic) way. Negative CJB is observed in depression and anxiety, conditions that burden affected individuals and their caregivers. Pre-clinical animal research is key to understanding CJB and developing therapies for affective and anxiety disorders, so a translationally relevant CJB test would be a useful addition to the existing pre-clinical rodent touchscreen test battery. Here, a CJB task in mouse touchscreen operant chambers was adapted and validated using pharmacological agents, bupropion and tetrabenazine, known to induce positive and negative CJB, respectively. Further, negative shifts in CJB were observed following an injection procedure (handling and intraperitoneal injection with a saline solution), demonstrating the sensitivity of the task. Interestingly, whereas social isolation has been linked to changes in affective state in humans, 8 weeks of single-housing in mice did not alter CJB but did induce anxiety-like behaviour in an open field. Collectively, these results present a validated task to assess CJB in mice, which will facilitate future explorations into the underlying neurobiology and potential treatment of affective and anxiety disorders.

Background/Objectives: The association between vitamin D status and insulin resistance (IR) has been less studied among Asians, and it remains elusive whether calcium could modify such an association. We examined the association of serum 25-hydroxyvitamin D (25(OH)D) concentrations with IR markers and the potential effect modification by calcium intake among a Japanese population. Subjects/Methods: The authors analyzed data ( n= 494) from a cross-sectional survey conducted in 2009 among a Japanese working population aged 20–68 years. Fasting serum 25(OH)D and insulin, as well as fasting plasma glucose were determined, and homeostatic model assessment of IR (HOMA-IR) was calculated. Calcium intake was assessed using a validated diet history questionnaire. Multiple linear regression was done with adjustment of potential confounding variables. Results: Fasting insulin and HOMA-IR were significantly inversely associated with 25(OH)D concentration across quartiles of 25(OH)D after fully adjusting for covariates ( P trend =0.04 and 0.02, respectively). Across clinically relevant categories of 25(OH)D, compared with participants in the vitamin D sufficiency group, those in the vitamin D insufficiency group had a 5% higher HOMA-IR score, and those in the hypovitaminosis D group had an 18% higher HOMA-IR score ( P trend =0.01). In an analysis by calcium intake, the HOMA-IR score was highest among participants with both a low calcium intake and lowest 25(OH)D concentrations, with significant inverse trend being observed in the group with lower calcium intake ( P trend =0.02). Conclusions: Our findings suggest that low vitamin D status is associated with IR among Japanese adults.

Aims/hypothesis Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes. Methods The beta cell function of 118 patients with type 1 diabetes of duration of 0.75–4.97 years was tested using a standardised liquid mixed meal test (MMT). Serum samples obtained at −5 to 120 min were analysed by multiplex bead-based technology for proinflammatory (IL-6, TNF-α), anti-inflammatory (IL-1 receptor antagonist [IL-1RA]) and regulatory (IL-10, TGF-β 1–3 ) cytokines, and by standard procedures for C-peptide. Differences in beta cell function between patient groups were assessed using stepwise multiple regression analysis adjusting for sex, age, duration of diabetes, BMI, HbA 1c and fasting blood glucose. Results High fasting systemic concentrations of the proinflammatory cytokines IL-6 and TNF-α were associated with increased fasting and stimulated C-peptide concentrations even after adjustment for confounders ( p  < 0.03). Interestingly, increased concentrations of anti-inflammatory/regulatory IL-1RA, IL-10, TGF-β 1 and TGF-β 2 were associated with lower fasting and stimulated C-peptide levels ( p  < 0.04), losing significance on adjustment for anthropometric variables. During the MMT, circulating concentrations of IL-6 and TNF-α increased ( p  < 0.001) while those of IL-10 and TGF-β 1 decreased ( p  < 0.02) and IL-1RA and TGF-β 2 remained unchanged. Conclusions/interpretation The association between better preserved beta cell function in longer term type 1 diabetes and increased systemic proinflammatory cytokines and decreased anti-inflammatory and regulatory cytokines is suggestive of ongoing inflammatory disease activity that might be perpetuated by the remaining beta cells. These findings should be considered when designing immune intervention studies aimed at patients with longer term type 1 diabetes and residual beta cell function.

Background/objectives: Vitamin B6 is suggested to have a protective role against depression. However, the association between vitamin B6 intake and depression remains inconclusive, and few studies have examined the relationship between circulating vitamin B6 concentrations and depressive symptoms. Here, we investigated the cross-sectional and prospective associations between serum pyridoxal concentrations and depressive symptoms among Japanese workers. Subjects/methods: Participants were 422 municipal employees (aged 21–67 years) who participated in a baseline survey in 2006 for cross-sectional analysis, and 210 subjects without depressive symptoms at baseline (2006) who completed both baseline and follow-up (2009) surveys for prospective analysis. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression analysis was used to estimate the odds ratio of depressive symptoms (CES-D scale of ⩾19) according to tertile of serum pyridoxal with adjustment for potential confounding variables. Results: In the cross-sectional analysis, serum pyridoxal concentrations were significantly associated with a decreased prevalence of depressive symptoms ( P for trend=0.03); the multivariable-adjusted odds ratio of depressive symptoms for the highest tertile of pyridoxal was 0.54 (95% confidence interval 0.30–0.96) compared with the lowest tertile. In longitudinal analyses, higher serum pyridoxal concentrations at baseline were associated with a trend toward reduced depressive symptoms after 3 years; the multivariable-adjusted odds ratio of depressive symptoms for the highest versus the lowest tertile of pyridoxal concentration was 0.55 (95% confidence interval 0.13–2.32). Conclusions: A higher vitamin B6 status may be associated with a decreased risk of depressive symptoms in Japanese.

AimsTo assess the association between physical activity (PA) during pregnancy and the prevalence of gestational diabetes mellitus (GDM) accounting for sitting time.MethodsThe study used data from a cohort study of 2030 pregnant women in Vietnam. Women were recruited from six hospitals in Ha Noi, Hai Phong, and Ho Chi Minh City. Baseline measurements including PA and GDM were taken at 24–28 weeks of gestation. PA was assessed during the past 3 months before the interview using the interviewer-administered Pregnancy Physical Activity Questionnaire. GDM was diagnosed at 24–28 weeks of gestation using the 2013 World Health Organization criteria.Results1987 out of 2030 pregnant women were included in the final analysis, of which 432 had GDM (21.7%). Women undertaking the highest level (upper tertile) of PA during pregnancy appeared to have a lower risk of GDM [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.53–0.94, Ptrend 0.017] when compared to those at the lowest tertile of PA. Similarly, women with increased levels of moderate-intensive activity and household/caregiving activity during pregnancy were associated with reduced risks of GDM (OR 0.66, 95% CI 0.50–0.86, Ptrend 0.002 and OR 0.72, 95% CI 0.55–0.95, Ptrend 0.020, respectively). These apparent inverse associations were not attenuated by their sitting time. There were no significant associations between sitting time, light-intensity activity, vigorous-intensity activity, occupation, sports/exercise, commuting, or meeting exercise guidelines and GDM risk.ConclusionsHigh levels of PA, particularly moderate-intensity and household/caregiving activities during pregnancy were associated with a lower prevalence of GDM independent of sitting time.

Background/Objectives: Although adipokines and insulin resistance are known to be correlated with body fatness, it is unclear whether they are independently related to weight gain experience. We examined the associations of serum adipokines and marker of insulin resistance with past weight gain during adulthood by taking the degree of attained body mass index (BMI) level into consideration. Subjects/Methods: Subjects were 399 Japanese municipal employees, aged ⩾30 years, who participated in a health survey. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Weight change during adulthood was calculated as the difference between measured current weight and recalled weight at the age of 20 years. Multiple regression was performed to calculate mean adipokine levels and homeostasis model assessment of insulin resistance (HOMA-IR) according to weight gain (<5 kg, 5–9.9 kg, or ⩾10 kg) with adjustment for current BMI. Results: Weight gain from the age of 20 years was significantly and positively associated with leptin levels even after adjustment for current BMI ( P for trend <0.001), whereas it was significantly and inversely associated with adiponectin levels in a BMI-adjusted model among subjects aged ⩾40 years ( P for trend=0.03). Weight gain was associated with HOMA-IR in a BMI-unadjusted model ( P for trend <0.001), but this association was largely attenuated after adjustment for BMI. Resistin, plasminogen activator inhibitor-1 and visfatin were not associated with past weight gain. Conclusions: Results suggest that a large weight gain during adulthood is associated with higher leptin and lower adiponectin levels independently of the degree of attained BMI level.

Purpose To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d’Urologie and International Consultation on Urological Diseases. Methods A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. Results The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. Conclusions The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.

The paper discusses flow modeling in closed-loop sewage systems. These systems take place in reconstruction and development of sewage systems. The waste flow values which are distributed over individual closed-loop sewers are proposed to be determined on the basis of the solution of the conservation equation for mass and energy. This article presents these equations for the cases of pressure-flow and free-flow of drains and calculating examples of all these cases. The issues of improving the reliability of sewage systems by transferring them to a closed-loop structure are considered.