PLoS medicine
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Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated. ⋯ A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.
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Transplacental transfer of maternal immunoglobulin G (IgG) to the fetus helps to protect against malaria and other infections in infancy. Recent studies have emphasized the important role of malaria-specific IgG3 in malaria immunity, and its transfer may reduce the risk of malaria in infancy. Human IgGs are actively transferred across the placenta by binding the neonatal Fc receptor (FcRn) expressed within the endosomes of the syncytiotrophoblastic membrane. Histidine at position 435 (H435) provides for optimal Fc-IgG binding. In contrast to other IgG subclasses, IgG3 is highly polymorphic and usually contains an arginine at position 435, which reduces its binding affinity to FcRn in vitro. The reduced binding to FcRn is associated with reduced transplacental transfer and reduced half-life of IgG3 in vivo. Some haplotypes of IgG3 have histidine at position 435. This study examines the hypotheses that the IgG3-H435 variant promotes increased transplacental transfer of malaria-specific antibodies and a prolonged IgG3 half-life in infants and that its presence correlates with protection against clinical malaria during infancy. ⋯ An arginine-to-histidine replacement at residue 435 in the binding domain of IgG3 to FcRn increases the transplacental transfer and half-life of malaria-specific IgG3 in young infants and is associated with reduced risk of clinical malaria during infancy. The IgG3-H435 allele may be under positive selection, given its relatively high frequency in malaria endemic areas.
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Prior research suggests that United States governmental sources documenting the number of law-enforcement-related deaths (i.e., fatalities due to injuries inflicted by law enforcement officers) undercount these incidents. The National Vital Statistics System (NVSS), administered by the federal government and based on state death certificate data, identifies such deaths by assigning them diagnostic codes corresponding to "legal intervention" in accordance with the International Classification of Diseases-10th Revision (ICD-10). Newer, nongovernmental databases track law-enforcement-related deaths by compiling news media reports and provide an opportunity to assess the magnitude and determinants of suspected NVSS underreporting. Our a priori hypotheses were that underreporting by the NVSS would exceed that by the news media sources, and that underreporting rates would be higher for decedents of color versus white, decedents in lower versus higher income counties, decedents killed by non-firearm (e.g., Taser) versus firearm mechanisms, and deaths recorded by a medical examiner versus coroner. ⋯ The media-based source, The Counted, reported a considerably higher proportion of law-enforcement-related deaths than the NVSS, which failed to report a majority of these incidents. For the NVSS, rates of underreporting were higher in lower income counties and for decedents killed by non-firearm mechanisms. There was no evidence suggesting that underreporting varied by death investigator type (medical examiner versus coroner) or race/ethnicity.
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Intensive blood pressure (BP) treatment can avert cardiovascular disease (CVD) events but can cause some serious adverse events. We sought to develop and validate risk models for predicting absolute risk difference (increased risk or decreased risk) for CVD events and serious adverse events from intensive BP therapy. A secondary aim was to test if the statistical method of elastic net regularization would improve the estimation of risk models for predicting absolute risk difference, as compared to a traditional backwards variable selection approach. ⋯ We found that predictive models could help identify subgroups of participants in both SPRINT and ACCORD-BP who had lower versus higher ARRs in CVD events/deaths with intensive BP treatment, and participants who had lower versus higher ARIs in serious adverse events.
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In a Perspective on the research article by Didelot and colleagues, Magnus Unemo and Christian Althaus discuss the value of modelling studies to inform antimicrobial resistance management and the limitations of the current evidence base informing such models.