Early childhood is a critical stage for the foundation and development of both the microbiome and host. Early-life antibiotic exposures, cesarean section, and formula feeding could disrupt microbiome establishment and adversely affect health later in life. We profiled microbial development during the first two years of life in a cohort of 43 US infants, and identify multiple disturbances associated with antibiotic exposures, cesarean section, and diet. Antibiotics delayed microbiome development and suppressed Clostridiales, including Lachnospiraceae. Cesarean section led to depleted Bacteroidetes populations, altering establishment of maternal bacteria. Formula-feeding was associated with age-dependent diversity deviations. These findings illustrate the complexity of early-life microbiome development, and microbiota disturbances with antibiotic use, cesarean section, and formula feeding that may contribute to obesity, asthma, and other disorders.
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.
BackgroundLifetime stroke risk has been calculated in a limited number of selected populations. We determined lifetime risk of stroke globally and at the regional and country level.MethodsUsing Global Burden of Disease Study estimates of stroke incidence and the competing risks of non-stroke mortality, we estimated the cumulative lifetime risk of ischemic stroke, hemorrhagic stroke, and total stroke (with 95% uncertainty intervals [UI]) for 195 countries among adults over 25 years) for the years 1990 and 2016 and according to the GBD Study Socio-Demographic Index (SDI).ResultsThe global estimated lifetime risk of stroke from age 25 onward was 24.9% (95% UI: 23.5–26.2): 24.7% (23.3–26.0) in men and 25.1% (23.7–26.5) in women. The lifetime risk of ischemic stroke was 18.3% and of hemorrhagic stroke was 8.2%. The risk of stroke was 23.5% in high SDI countries, 31.1% in high-middle SDI countries, and 13.2% in low SDI countries with UIs not overlapping for these categories. The greatest estimated risk of stroke was in East Asia (38.8%) and Central and Eastern Europe (31.7 and 31.6 %%), and lowest in Eastern Sub-Saharan Africa (11.8%). From 1990 to 2016, there was a relative increase of 8.9% in global lifetime risk.ConclusionsThe global lifetime risk of stroke is approximately 25% starting at age 25 in both men and women. There is geographical variation in the lifetime risk of stroke, with particularly high risk in East Asia, Central and Eastern Europe.
Summary Background Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35–77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. Methods In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18–75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. Findings 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10·1–50·0 μg/L, 50·1–150·0 μg/L, and 150·1–864·0 μg/L with at least 10·0 μg/L in well water were 1·34 (95% CI 0·99–1·82), 1·09 (0·81–1·47), and 1·68 (1·26–2·23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. Interpretation Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. Funding US National Institutes of Health.
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