White matter hyperintensity volume, local efficiency, and information processing speed scores are interrelated, and local network alterations as response to white matter abnormality explain detrime... Background Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matt...

Aims/hypothesis: Biomarkers of endothelial dysfunction and low-grade inflammation are important in the pathogenesis of CVD and can potentially be modified by physical activity and sedentary behaviour. Effects of physical activity on biomarkers of endothelial dysfunction may be especially prominent in type 2 diabetes. Methods: In the population-based Maastricht Study (n = 2363, 51.5% male, 28.3% type 2 diabetes, 15.1% prediabetes [defined as impaired glucose tolerance and impaired fasting glucose]), we determined biomarkers of endothelial dysfunction and low-grade inflammation, and combined z scores were calculated. Physical activity and sedentary behaviour were measured by activPAL. Linear regression analyses were used with adjustment for demographic, lifestyle and cardiovascular risk factors. Results: The association between total, light, moderate-to-vigorous and vigorous intensity physical activity and sedentary time on the one hand and biomarkers of endothelial dysfunction on the other were generally significant and were consistently stronger in prediabetes and type 2 diabetes as compared with normal glucose metabolism status (p for interaction 0.05). Conclusions/interpretation: Physical activity and sedentary behaviour are associated with biomarkers of endothelial dysfunction and low-grade inflammation. For biomarkers of endothelial dysfunction, associations between physical activity and sedentary behaviour were consistently stronger in (pre)diabetes than in normal glucose metabolism. Whether increasing physical activity or decreasing sedentary time can positively influence biomarkers of endothelial dysfunction in individuals with prediabetes and type 2 diabetes requires further study. Graphical

Purpose The role of diet in bladder carcinogenesis has yet to be established. To date most studies have investigated dietary components individually, rather than as dietary patterns, which may provide stronger evidence for any influence of diet on bladder carcinogenesis. The Mediterranean diet has been associated with many health benefits, but few studies have investigated its association with bladder cancer risk. Methods We investigated the potential association between the Mediterranean diet score (MDS) and risk of developing bladder cancer by pooling 13 prospective cohort studies included in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study and applying a Cox regression analysis. Results Dietary data from 646,222 study participants, including 3639 incident bladder cancer cases, were analysed. We observed an inverse association between Mediterranean diet and bladder cancer risk (HR_high 0.85 [95% CI 0.77, 0.93]). When stratifying the results on non-muscle-invasive or muscle-invasive disease or sex the association remained similar and the HR estimate was consistently below 1.00 both for medium and high adherence to the Mediterranean diet. A consistent association was observed when disregarding fat or alcohol intake. Conclusion We found evidence that adherence to the Mediterranean diet was associated with reduced risk of developing bladder cancer, suggesting a positive effect of the diet as a whole and not just one component.

Summary The P2X₇ receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X₇ receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X₇ receptor and the risk of osteoporosis. Introduction The purpose of this study was to determine whether genetic variation in the P2X₇ receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients. Methods Six hundred ninety women and 231 men aged ≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck. Results Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p = 0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p = 0.018 and p = 0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40 % decrease in risk of a lower T-score value (OR = 0.58 [95%CI, 0.33–1.00]). Conclusion Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment.

Higher intakes of whole grains and dietary fiber have been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for cancer. Because the evidence of association with bladder cancer (BC) is limited, we aimed to assess associations with BC risk for intakes of whole grains, refined grains, and dietary fiber. We pooled individual data from 574,726 participants in 13 cohort studies, 3214 of whom developed incident BC. HRs, with corresponding 95% CIs, were estimated using Cox regression models stratified on cohort. Dose–response relations were examined using fractional polynomial regression models. We found that higher intake of total whole grain was associated with lower risk of BC (comparing highest with lowest intake tertile: HR: 0.87; 95% CI: 0.77, 0.98; HR per 1-SD increment: 0.95; 95% CI: 0.91, 0.99; P for trend: 0.023). No association was observed for intake of total refined grain. Intake of total dietary fiber was also inversely associated with BC risk (comparing highest with lowest intake tertile: HR: 0.86; 95% CI: 0.76, 0.98; HR per 1-SD increment: 0.91; 95% CI: 0.82, 0.98; P for trend: 0.021). In addition, dose–response analyses gave estimated HRs of 0.97 (95% CI: 0.95, 0.99) for intake of total whole grain and 0.96 (95% CI: 0.94, 0.98) for intake of total dietary fiber per 5-g daily increment. When considered jointly, highest intake of whole grains with the highest intake of dietary fiber showed 28% reduced risk (95% CI: 0.54, 0.93; P for trend: 0.031) of BC compared with the lowest intakes, suggesting potential synergism. Higher intakes of total whole grain and total dietary fiber are associated with reduced risk of BC individually and jointly. Further studies are needed to clarify the underlying mechanisms for these findings.

Tea has been shown to be associated with reduced risk of several diseases including cardiovascular diseases, stroke, metabolic syndrome, and obesity. However, the results on the relationship between tea consumption and bladder cancer are conflicting. This research aimed to assess the association between tea consumption and risk of bladder cancer using a pooled analysis of prospective cohort data. Individual data from 532,949 participants in 12 cohort studies, were pooled for analyses. Cox regression models stratified by study centre was used to estimate hazard ratios (HR) and corresponding 95% CIs. Fractional polynomial regression models were used to examine the dose-response relationship. A higher level of tea consumption was associated with lower risk of bladder cancer incidence (compared with no tea consumption: HR = 0.87, 95% C.I. = 0.77-0.98 for low consumption; HR = 0.86, 95% C.I. = 0.77-0.96 for moderate consumption; HR = 0.84, 95% C.I. = 0.75-0.95 for high consumption). When stratified by sex and smoking status, this reduced risk was statistically significant among men and current and former smokers. In addition, dose-response analyses showed a lower bladder cancer risk with increment of 100 ml of tea consumption per day (HR-increment = 0.97; 95% CI = 0.96-0.98). A similar inverse association was found among males, current and former smokers while never smokers and females showed non-significant results, suggesting potential sex-dependent effect. Higher consumption of tea is associated with reduced risk of bladder cancer with potential interaction with sex and smoking status. Further studies are needed to clarify the mechanisms for a protective effect of tea (e.g. inhibition of the survival and proliferation of cancer cells and anti-inflammatory mechanisms) and its interaction with smoking and sex.