The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30–69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11–1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.

Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework.

India’s national COVID death totals remain undetermined. Using an independent nationally representative survey of 0.14 million (M) adults, we compared COVID mortality during the 2020 and 2021 viral waves to expected all-cause mortality. COVID constituted 29% (95% confidence interval, 28 to 31%) of deaths from June 2020 to July 2021, corresponding to 3.2 M (3.1 to 3.4) deaths, of which 2.7 M (2.6 to 2.9) occurred in April to July 2021 (when COVID doubled all-cause mortality). A subsurvey of 57,000 adults showed similar temporal increases in mortality, with COVID and non-COVID deaths peaking similarly. Two government data sources found that, when compared to prepandemic periods, all-cause mortality was 27% (23 to 32%) higher in 0.2 M health facilities and 26% (21 to 31%) higher in civil registration deaths in 10 states; both increases occurred mostly in 2021. The analyses find that India’s cumulative COVID deaths by September 2021 were six to seven times higher than reported officially.

Understanding how plant species coexist in tropical rainforests is one of the biggest challenges in community ecology. One prominent hypothesis suggests that rare species are at an advantage because trees have lower survival in areas of high conspecific density due to increased attack by natural enemies, a process known as negative density dependence (NDD). A consensus is emerging that NDD is important for plant‐species coexistence in tropical forests. Most evidence comes from short‐term studies, but testing the prediction that NDD decreases the spatial aggregation of tree populations provides a long‐term perspective. While spatial distributions have provided only weak evidence for NDD so far, the opposing effects of environmental heterogeneity might have confounded previous analyses. Here we use a novel statistical technique to control for environmental heterogeneity while testing whether spatial aggregation decreases with tree size in four tropical forests. We provide evidence for NDD in 22% of the 139 tree species analyzed and show that environmental heterogeneity can obscure the spatial signal of NDD. Environmental heterogeneity contributed to aggregation in 84% of species. We conclude that both biotic interactions and environmental heterogeneity play crucial roles in shaping tree dynamics in tropical forests.

Background—: Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease. Recent evidence indicates that PCSK9 also modulates the metabolism of triglyceride-rich apolipoprotein B (apoB) lipoproteins, another important coronary heart disease risk factor. Here, we studied the effects of physiological levels of PCSK9 on intestinal triglyceride-rich apoB lipoprotein production and elucidated for the first time the cellular and molecular mechanisms involved. Methods and Results—: Treatment of human enterocytes (CaCo-2 cells) with recombinant human PCSK9 (10 μg/mL for 24 hours) increased cellular and secreted apoB48 and apoB100 by 40% to 55% each ( P <0.01 versus untreated cells), whereas short-term deletion of PCSK9 expression reversed this effect. PCSK9 stimulation of apoB was due to a 1.5-fold increase in apoB mRNA ( P <0.01) and to enhanced apoB protein stability through both LDLR-dependent and LDLR-independent mechanisms. PCSK9 decreased LDLR protein ( P <0.01) and increased cellular apoB stability via activation of microsomal triglyceride transfer protein. PCSK9 also increased levels of the lipid-generating enzymes FAS, SCD , and DGAT2 ( P <0.05). In mice, human PCSK9 at physiological levels increased intestinal microsomal triglyceride transfer protein levels and activity regardless of LDLR expression. Conclusions—: PCSK9 markedly increases intestinal triglyceride-rich apoB production through mechanisms mediated in part by transcriptional effects on apoB, microsomal triglyceride transfer protein, and lipogenic genes and in part by posttranscriptional effects on the LDLR and microsomal triglyceride transfer protein. These findings indicate that targeted PCSK9-based therapies may also be effective in the management of postprandial hypertriglyceridemia.