Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the ...essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.
Abstract Childhood obesity is a global concern. The objectives of this meta-analytical study were to evaluate the effectiveness of school-based childhood obesity prevention programs, and to examine ...program components (moderators). The methods included searching databases (PubMed, Google Scholar, and the university's EBSCOhost Web service) as well as handsearching reference lists of articles published in English. Selection criteria for studies to be included in the meta-analysis were limited to studies that reported body mass index (BMI) or skinfold thickness as outcome measures and were school-based obesity prevention interventions; cross-sectional design studies were excluded. We hypothesized the meta-analysis would yield a summary effect size of magnitude which would indicate that school-based interventions have been effective in improving children's BMI or skinfold thickness values. A total of 26 114 children from 27 school-based childhood obesity prevention programs provided 54 effect sizes. A random-effects model calculated a small summary effect size of 0.039 (95% confidence interval −0.013 to 0.092). Heterogeneity among studies was observed which disappeared after pooling studies that used a randomized controlled trial design with one program moderator (physical activity or nutrition). We failed to accept our hypothesis and concluded that overall, school-based interventions have not been effective for improving body mass index or skinfold thickness to curb childhood obesity; however, randomized controlled trials that focused on physical activity or nutrition appeared to produce promising results.
To assess minority college undergraduate and graduate students' self-reported stress, ethnic identity, and skin complexion as predictors of perceptions of racial discrimination.
The participants (N = ...172) were college-aged minority students. A hierarchical multiple regression analysis was conducted to examine the predictive relationship of the study variables on perceived racial discrimination.
Skin complexion (β = .34, p < .05) and ethnic identity (β = .25, p < .05) had a positive (increased frequency) relationship with racial discrimination. When separated by sex, stress was a statistically significant predictor β = .24, p < .05) of racial discrimination for males only.
Understanding the predictors of perceived racial discrimination may allow for the development of interventions that alleviate the stress associated with discrimination.
Noble gases record fluid interactions in multiphase subsurface environments through fractionation processes during fluid equilibration. Water in the presence of hydrocarbons at the subsurface ...acquires a distinct elemental signature due to the difference in solubility between these two fluids. We find the atmospheric noble gas signature in produced water is partially preserved after hydrocarbons production and water disposal to unlined ponds at the surface. This signature is distinct from meteoric water and can be used to trace oil-field water seepage into groundwater aquifers. We analyse groundwater (n = 30) and fluid disposal pond (n = 2) samples from areas overlying or adjacent to the Fruitvale, Lost Hills, and South Belridge Oil Fields in the San Joaquin Basin, California, USA. Methane (2.8 × 10−7 to 3 × 10−2 cm3 STP/cm3) was detected in 27 of 30 groundwater samples. Using atmospheric noble gas signatures, the presence of oil-field water was identified in 3 samples, which had equilibrated with thermogenic hydrocarbons in the reservoir. Two (of the three) samples also had a shallow microbial methane component, acquired when produced water was deposited in a disposal pond at the surface. An additional 6 samples contained benzene and toluene, indicative of interaction with oil-field water; however, the noble gas signatures of these samples are not anomalous. Based on low tritium and 14C contents (≤ 0.3 TU and 0.87–6.9 pcm, respectively), the source of oil-field water is likely deep, which could include both anthropogenic and natural processes. Incorporating noble gas analytical techniques into the groundwater monitoring programme allows us to 1) differentiate between thermogenic and microbial hydrocarbon gas sources in instances when methane isotope data are unavailable, 2) identify the carrier phase of oil-field constituents in the aquifer (gas, oil-field water, or a combination), and 3) differentiate between leakage from a surface source (disposal ponds) and from the hydrocarbon reservoir (either along natural or anthropogenic pathways such as faulty wells).
Obesity is a national health concern and the focus of many health promotion programs. The purpose of this study was to evaluate the behavioral impact of a 12-week obesity prevention program on a ...university campus. Participants were provided questionnaires with weights, heights, and body mass indices (BMIs) determined at the pre-phase weigh-in and post-phase weigh-out. At the weigh-in, participants received pedometers and information about upcoming educational sessions to assist them with reaching their health behavior goals. A total of 247 (38.2% of 646) individuals (79.4% women) completed the program. A mean weight loss of 1.8 kg caused a decrease in BMI from 29.3 at weigh-in to 28.7 at weigh-out (p = .002). Pre- and post-questionnaires indicated increases (p < 0.001) in physical activity; using pedometers; and intakes of fruits, vegetables, and water at the end of the program. The 6-month follow-up questionnaire (33.2% response rate) indicated healthy habits were being maintained for fruit and vegetable consumption. Further intervention development to incorporate innovative strategies for promoting healthy behaviors among students and employees on university campuses could help decrease the prevalence of obesity.
Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other ...surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures.
The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations.
Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to "no prophylaxis" strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results.
The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 95% CI: -£784 to £1,103, probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 95% CI: -£101 to £665; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs.
For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.
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