Common protein-coding variants influence the racing phenotype in galloping racehorse breeds.

Selection for system-wide morphological, physiological, and metabolic adaptations has led to extreme athletic phenotypes among geographically diverse horse breeds. Here, we identify genes contributing to exercise adaptation in racehorses by applying genomics approaches for racing performance, an end-point athletic phenotype. Using an integrative genomics strategy to first combine population genomics results with skeletal muscle exercise and training transcriptomic data, followed by whole-genome resequencing of Asian horses, we identify protein-coding variants in genes of interest in galloping racehorse breeds (Arabian, Mongolian and Thoroughbred). A core set of genes, G6PC2, HDAC9, KTN1, MYLK2, NTM, SLC16A1 and SYNDIG1, with central roles in muscle, metabolism, and neurobiology, are key drivers of the racing phenotype. Although racing potential is a multifactorial trait, the genomic architecture shaping the common athletic phenotype in horse populations bred for racing provides evidence for the influence of protein-coding variants in fundamental exercise-relevant genes. Variation in these genes may therefore be exploited for genetic improvement of horse populations towards specific types of racing.

Resistance-associated substitution and ledipasvir/sofosbuvir therapy in Mongolian chronic hepatitis C patients.

BACKGROUND: Mongolia has the highest prevalence of hepatitis C virus (HCV) infection worldwide. Ledipasvir/sofosbuvir (LDV/SOF) was introduced to Mongolia since 2016 for HCV eradication. It has been reported that HCV resistance-associated substitutions (RASs) would affect the effectiveness of LDV/SOF in western chronic hepatitis C (CHC) patients. We thus investigated the effectiveness of LDV/SOF and the impact of RAS on the treatment outcome in Mongolian CHC patients. METHODS: Patients with genotype (GT) 1b HCV infection were prospectively enrolled in Mongolia and treated with LDV/SOF for 12 weeks. The proportion of pre-treatment NS5A Y93H RAS in viral quasispecies was measured with next-generation sequencing. The endpoint of LDV/SOF effectiveness was sustained virological response at post-treatment week 12 (SVR12). RESULTS: A total of 94 CHC patients were evaluated. The baseline Y93H proportion was <1% in 74 patients, 1-15% in 7, 15-50% in 2, and ≥50% in 11. All patients completed 12-week LDV/SOF treatment and the SVR rate was 90.4%. The rate of failure to achieve SVR12 for patients with Y93H < 1%, 1-15%, and ≥15% were 0%, 14.3%, and 61.5%, respectively (p for trend = 0.001). In univariable analysis, older age, baseline alanine transaminase level <40 U/mL, and a higher proportion of Y93H were associated with treatment failure. In multivariable analysis, only a higher proportion of Y93H was associated with treatment failure (p = 0.022). CONCLUSION: LDV/SOF therapy achieves a high SVR rate in Mongolian CHC GT1b patients without baseline Y93H RAS. A higher proportion of Y93H may severely undermine the effectiveness of LDV/SOF.

Empanelment: A foundational component of primary health care.

Empanelment is a foundational strategy for building or improving primary health care systems and a critical pathway for achieving effective universal health coverage. However, there is little international guidance for defining empanelment or understanding how to implement empanelment systems in low- and middle-income countries. To fill this gap, a multi-country collaborative within the Joint Learning Network for Universal Health Coverage developed this empanelment overview, proposing a people-centered definition of empanelment that reflects the responsibility to proactively deliver primary care services to all individuals in a target population. This document, building on existing literature on empanelment and representing input from 10 countries, establishes standard concepts of empanelment and describes why and how empanelment is used. Finally, it identifies key domains that may influence effective empanelment and that must be considered in deciding how empanelment can be implemented. This document is designed to be a useful resource for health policymakers, planners and decision-makers in ministries of health, as well as front line providers of primary care service delivery who are working to ensure quality people-centered primary care to everyone everywhere.

Impact of Seasonal Winter Air Pollution on Health across the Lifespan in Mongolia and Some Putative Solutions.

Environmental pollution of the air, water, and soil comprise an increasingly urgent challenge to global health, well-being, and productivity. The impact of environmental pollution arguably has its greatest impact across the lifespan on children, women of childbearing age, and pregnant women and their unborn children, not only because of their vulnerability during development, but also because of their subsequent longevity. Ulaanbaatar, Mongolia, is a highly instructive, perhaps extreme, example of what happens with recent, rapid urbanization. It is the coldest capital city on Earth, where average ambient temperatures routinely fall below -40°C/F between November and February. During the cold winter period, more than 200,000 "Gers" (traditional felt-lined dwellings) in the "Ger district" burn over 600,000 tons of coal for domestic heating (>3 tons each). Thus, outdoor ambient particulate levels frequently exceed 100 times the WHO-recommended safety level for sustained periods of time, and drive the majority of personal particulate matter exposure. Indoor levels of exposure are somewhat lower in this setting because Gers are equipped with chimneys. Major adverse health impacts that we have documented in the Ger districts include the following: respiratory diseases among those between 1 and 59 years of age and cardiac diseases in those over 60; alarming increases in lung cancer rates in females are also beginning to emerge; and fertility and subsequent successful completion of term pregnancy falls by up to half during the winter pollution season, while early fetal death rises by fourfold. However, the World Bank has intervened with a Ger stove replacement project that has progressively reduced winter pollution by about 30% over the past 5 years, and this has been accompanied by an increase in mean term birth weight of up to 100g. Each incremental decrement in air pollution clearly has beneficial effects on pregnancy, which are likely to have the greatest positive health and macroeconomic impact across the lifespan. However, innovative policies and solutions are clearly needed to eliminate coal heating in Gers and thus further reduce the markedly negative health impact of this practice.