Effect estimates derived from administrative units were smaller than those derived from tailored empirically derived buffer measures. Substantively, a 10% increase in the percentage of fast food restaurants using a "classic" network buffer was associated with a 6.3 (SE=1.17) point higher DIS (P< .001). The relationship between the percentage of supermarkets and DIS, however, was null. We observed high correlation coefficients between buffer-based density measures of supermarkets and fast food restaurants (r=0.73-0.83), which made it difficult to estimate independent associations by food outlet type. Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures. Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures. The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28±12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70ml dose per day of either BRJ (~12.5mmol nitrate per day; n=11) or non-nitrate calorie matched control (n=11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800m) reached on day 17 of the expedition. Data were collected at baseline (44m altitude), at 2350m (day 9), 3400m (day 12) and 4800m (day 17). BRJ enhanced the salivary levels of nitrite (p=0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800m in the control group (p=0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800m compared with baseline (p=0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p=0.61). BRJ did not affect the burden of HA illness (p=1.00). BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness. BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.Beta-cell death and dysfunction are involved in the development of type 1 and 2 diabetes. ER-stress impairs beta-cells function resulting in pro-apoptotic stimuli that promote cell death. Hence, the identification of protective mechanisms in response to ER-stress could lead to novel therapeutic targets and insight in the pathology of these diseases. Here, we report the identification of proteins involved in dysregulated pathways upon thapsigargin treatment of MIN6 cells. Utilizing quantitative proteomics we identified upregulation of proteins involved in protein folding, unfolded protein response, redox homeostasis, proteasome processes associated with endoplasmic reticulum and downregulation of TCA cycle, cellular respiration, lipid metabolism and ribosome assembly processes associated to mitochondria and eukaryotic initiation translation factor components. Subsequently, pro-inflammatory cytokine treatment was performed to mimic pathological changes observed in beta-cells during diabetes. https://www.selleckchem.com/products/disodium-r-2-hydroxyglutarate.html Cytokines induced ER stress and impaired mitochondrial function in beta-cells corroborating the results obtained with the proteomic approach. HSPB1 levels are increased by prolactin on pancreatic beta-cells and this protein is a key factor for cytoprotection although its role has not been fully elucidated. Here we show that while up-regulation of HSPB1 was able to restore the mitochondrial dysfunction induced by beta-cells' exposure to inflammatory cytokines, silencing of this chaperone abrogated the beneficial effects promoted by PRL. Taken together, our results outline the importance of HSPB1 to mitigate beta-cell dysfunction. Further studies are needed to elucidate its role in diabetes.Disrupted ovarian development induced by chemical exposure may impair fertility later in life. Since androgens are essential for early ovarian development, we speculated that perinatal exposure to a binary mixture of the known anti-androgens DEHP and procymidone could alter steroid synthesis, disrupt ovarian follicle recruitment and ultimately maturation in female rat offspring. Wistar rat dams were exposed by oral gavage from gestation day 7 to postnatatal day 22 to two mixture doses known to alter reproductive development in male offspring (low 10 mg/kg bw/day of procymidone and 30 mg/kg bw/day of DEHP; high 20 mg/kg bw/day of procymidone and 60 mg/kg bw/day of DEHP). The Effects on plasma steroid hormones, ovarian follicle distribution and expression of markers related to steroid synthesis were examined in female offspring. In prepubertal offspring, we observed an increased number of newly recruited (primary) follicles in exposed animals compared to controls, and the plasma steroid hormone profile was altered by exposure levels of progesterone, corticosterone and estrone were dose dependently elevated, whereas androgen levels were unaffected. In adulthood, a trend towards a smaller number of early-stage follicles may point to accelerated loss of follicle reserves, which is disconcerting. The changes in follicle distribution in exposed ovaries may reflect the combined influence of androgen receptor antagonism and altered ovarian steroid synthesis. This study adds to a growing body of evidence showing altered ovarian development following exposure to human relevant chemicals with possible severe consequences for female fertility.