Although eosinophils are considered useful in defense mechanisms against parasites, their exact function in innate immunity remains unclear. The aim of this study is to better understand the role of eosinophils within the gastrointestinal immune system. We show here that lipopolysaccharide from Gram-negative bacteria activates interleukin-5 (IL-5)- or interferon-gamma-primed eosinophils to release mitochondrial DNA in a reactive oxygen species-dependent manner, but independent of eosinophil death. Notably, the process of DNA release occurs rapidly in a catapult-like manner--in less than one second. In the extracellular space, the mitochondrial DNA and the granule proteins form extracellular structures able to bind and kill bacteria both in vitro and under inflammatory conditions in vivo. Moreover, after cecal ligation and puncture, Il5-transgenic but not wild-type mice show intestinal eosinophil infiltration and extracellular DNA deposition in association with protection against microbial sepsis. These data suggest a previously undescribed mechanism of eosinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage, preventing the host from uncontrolled invasion of bacteria.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS) including 26,488 cases and 83,964 controls of European, East Asian, South Asian, and Mexican and Mexican American ancestry. We observed significant excess in directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven novel T2D susceptibility loci. Furthermore, we observed considerable improvements in fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterisation of complex trait loci, and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Abstract Disrespect and abuse during childbirth are violations of women’s human rights and an indicator of poor-quality care. Disrespect and abuse during childbirth are widespread, yet data on providers’ perspectives on the topic are limited. We examined providers’ perspectives on the frequency and drivers of disrespect and abuse during facility-based childbirth in a rural county in Kenya. We used data from a mixed-methods study in a rural county in Western Kenya with 49 maternity providers (32 clinical and 17 non-clinical) in 2016. Providers were asked structured questions on disrespect and abuse, followed by open-ended questions on why certain behaviours were exhibited (or not). Most providers reported that women were often treated with dignity and respect. However, 53% of providers reported ever observing other providers verbally abuse women and 45% reported doing so themselves. Observation of physical abuse was reported by 37% of providers while 35% reported doing so themselves. Drivers of disrespect and abuse included perceptions of women being difficult, stress and burnout, facility culture and lack of accountability, poor facility infrastructure and lack of medicines and supplies, and provider attitudes. Provider bias, training and women’s empowerment influenced how different women were treated. We conclude that disrespect and abuse are driven by difficult situations in a health system coupled with a facilitating sociocultural environment. Providers resorted to disrespect and abuse as a means of gaining compliance when they were stressed and feeling helpless. Interventions to address disrespect and abuse need to tackle the multiplicity of contributing factors. These should include empowering providers to deal with difficult situations, develop positive coping mechanisms for stress and address their biases. We also need to change the culture in facilities and strengthen the health systems to address the system-level stressors.