Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Effect of stannous chloride combined with caffeine on fecundity of Drosophila prosaltans

The present study analyzed the number of progeny of stannous chloride- and/or caffeine-treated Drosophila prosaltans. A significant decreasing effect was observed in every case when compared to the control, except for the smallest stannous chloride dose used. Combinations of both substances using two different stannous chloride doses did not differ significantly from each other but number of progeny decreased 15% with the higher concentration combination when compared with caffeine-treated flies. The present results and data in the literature indicate that the effects of continuous ingestion of stannous chloride should be studied.<br>A fecundidade de Drosophila prosaltans foi analisada em indivíduos tratados com íon estanoso, cafeína ou íon estanoso, em duas concentrações, combinado com cafeína. Em todos os casos, a fecundidade foi significativamente menor quando comparada com o controle, exceto na menor concentração de íon estanoso. Nas combinações das duas substâncias, a redução não foi significativamente maior que a causada pela cafeína sozinha, podendo indicar que o efeito das duas substâncias juntas corresponde ao próprio efeito da cafeína separada. Mas a redução da fecundidade foi 15% maior no tratamento que utilizou íon estanoso em maior concentração, sugerindo que seu efeito tóxico nesse parâmetro, mesmo em combinação com a cafeína, não deve ser desconsiderado

Local boundary conditions for NMR-relaxation in digitized porous media

We narrow the gap between simulations of nuclear magnetic resonance dynamics on digital domains (such as CT-images) and measurements in D-dimensional porous media. We point out with two basic domains, the ball and the cube in D dimensions, that due to a digital uncertainty in representing the real pore surfaces of dimension D − 1, there is a systematic error in simulated dynamics. We then reduce this error by introducing local Robin boundary conditions