1965 US Voting Rights Act Impact on Black and Black Versus White Infant Death Rates in Jim Crow States, 1959-1980 and 2017-2021.

Objectives. To investigate the impact of the US Voting Rights Act (VRA) of 1965 on Black and Black versus White infant deaths in Jim Crow states. Methods. Using data from 1959 to 1980 and 2017 to 2021, we applied difference-in-differences methods to quantify differential pre-post VRA changes in infant deaths in VRA-exposed versus unexposed counties, controlling for population size and social, economic, and health system characteristics. VRA-exposed counties, identified by Section 4, were subject to government interventions to remove existing racist voter suppression policies. Results. Black infant deaths in VRA-exposed counties decreased by an average of 11.4 (95% confidence interval [CI] = 1.7, 21.0) additional deaths beyond the decrease experienced by unexposed counties between the pre-VRA period (1959-1965) and the post-VRA period (1966-1970). This translates to 6703 (95% CI = 999.6, 12 348) or 17.5% (95% CI = 3.1%, 28.1%) fewer deaths than would have been experienced in the absence of the VRA. The equivalent differential changes were not significant among the White or total population. Conclusions. Passage of the VRA led to pronounced reductions in Black infant deaths in Southern counties subject to government intervention because these counties had particularly egregious voter suppression practices. (Am J Public Health. 2024;114(3):300-308. https://doi.org/10.2105/AJPH.2023.307518).

How the news media activate public expression and influence national agendas.

We demonstrate that exposure to the news media causes Americans to take public stands on specific issues, join national policy conversations, and express themselves publicly-all key components of democratic politics-more often than they would otherwise. After recruiting 48 mostly small media outlets, we chose groups of these outlets to write and publish articles on subjects we approved, on dates we randomly assigned. We estimated the causal effect on proximal measures, such as website pageviews and Twitter discussion of the articles' specific subjects, and distal ones, such as national Twitter conversation in broad policy areas. Our intervention increased discussion in each broad policy area by ~62.7% (relative to a day's volume), accounting for 13,166 additional posts over the treatment week, with similar effects across population subgroups.

Development of a therapeutic monoclonal antibody that targets secreted fatty acid-binding protein aP2 to treat type 2 diabetes.

The lipid chaperone aP2/FABP4 has been implicated in the pathology of many immunometabolic diseases, including diabetes in humans, but aP2 has not yet been targeted for therapeutic applications. aP2 is not only an intracellular protein but also an active adipokine that contributes to hyperglycemia by promoting hepatic gluconeogenesis and interfering with peripheral insulin action. Serum aP2 levels are markedly elevated in mouse and human obesity and strongly correlate with metabolic complications. These observations raise the possibility of a new strategy to treat metabolic disease by targeting serum aP2 with a monoclonal antibody (mAb) to aP2. We evaluated mAbs to aP2 and identified one, CA33, that lowered fasting blood glucose, improved systemic glucose metabolism, increased systemic insulin sensitivity, and reduced fat mass and liver steatosis in obese mouse models. We examined the structure of the aP2-CA33 complex and resolved the target epitope by crystallographic studies in comparison to another mAb that lacked efficacy in vivo. In hyperinsulinemic-euglycemic clamp studies, we found that the antidiabetic effect of CA33 was predominantly linked to the regulation of hepatic glucose output and peripheral glucose utilization. The antibody had no effect in aP2-deficient mice, demonstrating its target specificity. We conclude that an aP2 mAb-mediated therapeutic constitutes a feasible approach for the treatment of diabetes.

Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production.

Proper control of hepatic glucose production is central to whole-body glucose homeostasis, and its disruption plays a major role in diabetes. Here, we demonstrate that although established as an intracellular lipid chaperone, aP2 is in fact actively secreted from adipocytes to control liver glucose metabolism. Secretion of aP2 from adipocytes is regulated by fasting- and lipolysis-related signals, and circulating aP2 levels are markedly elevated in mouse and human obesity. Recombinant aP2 stimulates glucose production and gluconeogenic activity in primary hepatocytes in vitro and in lean mice in vivo. In contrast, neutralization of secreted aP2 reduces glucose production and corrects the diabetic phenotype of obese mice. Hyperinsulinemic-euglycemic and pancreatic clamp studies upon aP2 administration or neutralization demonstrated actions of aP2 in liver. We conclude that aP2 is an adipokine linking adipocytes to hepatic glucose production and that neutralizing secreted aP2 may represent an effective therapeutic strategy against diabetes.

Mercury poisoning in a free-living northern river otter (Lontra canadensis).

A moribund 5-year-old female northern river otter (Lontra canadensis) was found on the bank of a river known to be extensively contaminated with mercury. It exhibited severe ataxia and scleral injection, made no attempt to flee, and died shortly thereafter of drowning. Tissue mercury levels were among the highest ever reported for a free-living terrestrial mammal: kidney, 353 microg/g; liver, 221 microg/g; muscle, 121 microg/g; brain (three replicates from cerebellum), 142, 151, 151 microg/g (all dry weights); and fur, 183 ug/g (fresh weight). Histopathologic findings including severe, diffuse, chronic glomerulosclerosis and moderate interstitial fibrosis were the presumptive cause of clinical signs and death. This is one of a few reports to document the death of a free-living mammal from presumed mercury poisoning.

A comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33.

Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r (2) threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r (2) threshold of 0.8 and MAF >5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression.

The movement of aquatic mercury through terrestrial food webs.

Mercury has contaminated rivers worldwide, with health consequences for aquatic organisms and humans who consume them. Researchers have focused on aquatic birds as sentinels for mercury. However, trophic transfer between adjacent ecosystems could lead to the export of aquatic mercury to terrestrial habitats. Along a mercury-contaminated river in Virginia, United States, terrestrial birds had significantly elevated levels of mercury in their blood, similar to their aquatic-feeding counterparts. Diet analysis revealed that spiders delivered much of the dietary mercury. We conclude that aquatic mercury pollution can move into terrestrial habitats, where it biomagnifies to levels in songbirds that may cause adverse effects. Rivers contaminated with mercury may pose a threat to the many bird species that feed on predatory invertebrates in adjacent riparian habitats.