Search

Background: One-carbon metabolism (OCM) is involved in RNA, DNA synthesis and in epigenetic regulation. Pathway gene analysis is more likely to capture potential gene-disease associations comparing to single gene analysis. We investigated whether genetic variants in folate network as well as their interactions would predict subsequent acute myocardial infarction (AMI) in patients undergoing elective coronary angiography for stable angina pectoris (SAP). Methods: A total of 2381 subjects (98% Caucasian) recruited to the Western Norway B Vitamin Intervention Trial (WENBIT) in 2000-2004 were studied. Patients were followed until a subsequent AMI or end of 2006. We genotyped 18 commonly investigated single nucleotide polymorphisms (SNPs) in 13 genes in the OCM network. Predictable variants were selected based on both out-of-bag importance scores from random survival forests and their incremental effects from recursive nested analysis. We then assessed gene-gene interactions among those predictive variants with generalized logistic model and calculated hazard ratio (HR), confidence interval (CI) for each predictor in Cox proportional hazard models. Results: There are 204 (8.57%) patients who experienced an AMI throughout 4.9 years (median) follow-up. We observed no violation from Hardy-Weinberg equilibrium in 15 SNPs in our population. Four SNPs (rs1076991, rs1021737, rs1801133 and rs3733890) in folate network were identified as promising candidates for predicting AMI risk. Interestingly, only rs1076991 associated significantly with AMI (HR=1.30, 95% CI: 1.10-1.52), indicating the other SNPs primarily mediate their risk bygene-gene interactions. There was a strong and stable interaction between the dominant model of rs3733890 and dominant model of rs34489327 (P for interaction: 0.003; HR =2.23, 95% CI: 1.27-3.92, adjusted for age, gender, smoking, diabetes mellitus, hypertension, extent of CAD by angiography (0-3), apolipoprotein (Apo) A1 and B, left ventricular ejection fraction and estimated glomerular filtration rate). Further adjustment for vitamins involved in OCM (folate, B2, B6, B12), the substrates (betaine and homocysteine) and products (methionine and dimethylglycine) of the betaine--homocysteine Smethyltransferase (BHMT) had minimal influence on the estimate. Conclusions: Prior studies show that BHMT transcription is associated with cotranscription of Apo B and that the rs3733890 of this gene is associated with higher dimethylglycine levels. We have recently shown that elevated plasma dimethylglycine is associated with increased risk of AMI and improves risk prediction in patients with SAP independent of Apo B levels. The current investigation extends previous knowledge, suggesting that a genetic variant in BHMT may modulate the risk of AMI by interfering with thymidylate synthesis independent of plasma dimethylglycine. [ABSTRACT FROM AUTHOR]

Background: Claims about what improves or harms our health are ubiquitous. People need to be able to assess the reliability of these claims. We aimed to evaluate an intervention designed to teach primary school children to assess claims about the effects of treatments (ie, any action intended to maintain or improve health).Methods: In this cluster-randomised controlled trial, we included primary schools in the central region of Uganda that taught year-5 children (aged 10-12 years). We excluded international schools, special needs schools for children with auditory and visual impairments, schools that had participated in user-testing and piloting of the resources, infant and nursery schools, adult education schools, and schools that were difficult for us to access in terms of travel time. We randomly allocated a representative sample of eligible schools to either an intervention or control group. Intervention schools received the Informed Health Choices primary school resources (textbooks, exercise books, and a teachers' guide). Teachers attended a 2 day introductory workshop and gave nine 80 min lessons during one school term. The lessons addressed 12 concepts essential to assessing claims about treatment effects and making informed health choices. We did not intervene in the control schools. The primary outcome, measured at the end of the school term, was the mean score on a test with two multiple-choice questions for each of the 12 concepts and the proportion of children with passing scores on the same test. This trial is registered with the Pan African Clinical Trial Registry, number PACTR201606001679337.Findings: Between April 11, 2016, and June 8, 2016, 2960 schools were assessed for eligibility; 2029 were eligible, and a random sample of 170 were invited to recruitment meetings. After recruitment meetings, 120 eligible schools consented and were randomly assigned to either the intervention group (n=60, 76 teachers and 6383 children) or control group (n=60, 67 teachers and 4430 children). The mean score in the multiple-choice test for the intervention schools was 62·4% (SD 18·8) compared with 43·1% (15·2) for the control schools (adjusted mean difference 20·0%, 95% CI 17·3-22·7; p<0·00001). In the intervention schools, 3967 (69%) of 5753 children achieved a predetermined passing score (≥13 of 24 correct answers) compared with 1186 (27%) of 4430 children in the control schools (adjusted difference 50%, 95% CI 44-55). The intervention was effective for children with different levels of reading skills, but was more effective for children with better reading skills.Interpretation: The use of the Informed Health Choices primary school learning resources, after an introductory workshop for the teachers, led to a large improvement in the ability of children to assess claims about the effects of treatments. The results show that it is possible to teach primary school children to think critically in schools with large student to teacher ratios and few resources. Future studies should address how to scale up use of the resources, long-term effects, including effects on actual health choices, transferability to other countries, and how to build on this programme with additional primary and secondary school learning resources.Funding: Research Council of Norway. [ABSTRACT FROM AUTHOR]

OBJECTIVE : We examined the effects of different concentrations of sodium fluoride on the morphological characteristics and the unfolded protein response signaling pathway (UPR) in rat ameloblasts. METHODS : Eighty Wistar rats were randomly divided into one control and three experimental groups. Rats in each group were fed with water containing fluoride ion (F) concentrations of <0.3 mg F/L (control), 50 mg F/L (low-dose group), 100 mg F/L (middle-dose group), and 150 mg F/L (high-dose group). After 12 weeks of treatment, the rats were killed and each mandible was dissected out for sectioning to observe the characteristic morphology of ameloblasts during tooth development by HE staining. Simultaneously, we analyzed the expression of immunoglobulin binding protein (BiP), X-box binding protein (XBP1), inositol-requiring enzyme 1 (XBIre1 α ), and activating transcription factor 6 (ATF6) in ameloblasts by in situ hybridization. RESULTS : The results indicated that fluoride affects the morphology and differentiation of ameloblasts during tooth development. The mRNA expression of BiP, XBP1, Ire1 α , and ATF6 increased significantly with increasing fluoride concentrations in drinking water (p<0.05 or p<0.01). In addition, the expression of these proteins increased gradually, but significantly, with tooth development in a dose-dependent manner in the experimental groups, particularly at the transition and maturity periods (p<0.05 or p<0.01). CONCLUSION : Our study suggests that fluoride undermined the morphology and differentiation of ameloblasts during tooth development and initiated an endoplasmic reticulum (ER) stress response. UPR responses play a role in the development of dental fluorosis and might lead to dental fluorosis. [ABSTRACT FROM AUTHOR]

Developing low cost and highly robust electrocatalysts for oxygen evolution reaction, hydrogen evolution reaction (HER), and oxygen reduction reaction (ORR) is of great importance for the efficient conversion of sustainable energy sources. Herein, we report a facile pyrolysis strategy for the controllable synthesis of NiCo@NiS/S-CNTs with NiCo@NiS nanoparticles anchored on sulfur-doped carbon nanotubes (CNTs). The obtained NiCo@NiS/S-CNT electrocatalyst exhibits excellent dual-functional catalytic activities under an alkaline condition, an ORR performance with an onset potential of −30 mV, and a half-wave potential of −150 mV (versus Ag/AgCl) while the overpotential for the HER is −1.16 V (versus Ag/AgCl) at a current density of 10 mA cm−2. It was found that the incorporation of sulfur can regulate the electronic structure of CNTs to accelerate the electron transfer performance and generate new catalytic sites, thus contributing to greatly enhancing both the activity and stability of the catalytic process. This work provides a promising way for the rational design of efficient and robust catalysts for sustainable energy conversion. [ABSTRACT FROM AUTHOR]