The people behind the papers - Wael Noor El-Nachef and Marianne Bronner

The enteric nervous system (ENS) derives from the neural crest and innervates the gastrointestinal system, in which it is essential for gut function throughout life. A new paper in Development uses zebrafish to investigate the poorly understood process of post-embryonic ENS neurogenesis, in both development and injury contexts. To find out more, we met the paper's two authors, Wael Noor El-Nachef, Assistant Clinical Professor of Medicine at UCLA, and Marianne Bronner, Albert Billings Ruddock Professor of Biology and Biological Engineering at Caltech

The people behind the papers - Wael Noor El-Nachef and Marianne Bronner

The enteric nervous system (ENS) derives from the neural crest and innervates the gastrointestinal system, in which it is essential for gut function throughout life. A new paper in Development uses zebrafish to investigate the poorly understood process of post-embryonic ENS neurogenesis, in both development and injury contexts. To find out more, we met the paper's two authors, Wael Noor El-Nachef, Assistant Clinical Professor of Medicine at UCLA, and Marianne Bronner, Albert Billings Ruddock Professor of Biology and Biological Engineering at Caltech

De novo enteric neurogenesis in post-embryonic zebrafish from Schwann cell precursors rather than resident cell types

The enteric nervous system (ENS) is essential for normal gastrointestinal function. Although the embryonic origin of enteric neurons from the neural crest is well established, conflicting evidence exists regarding postnatal enteric neurogenesis. Here, we address this by examining the origin of de novo neurogenesis in the post-embryonic zebrafish ENS. Although new neurons are added during growth and after injury, the larval intestine appears to lack resident neurogenic precursors or classical glia marked by sox10, plp1a, gfap or s100. Rather, lineage tracing with lipophilic dye or inducible Sox10-Cre suggests that post-embryonic enteric neurons arise from trunk neural crest-derived Schwann cell precursors that migrate from the spinal cord into the intestine. Furthermore, the 5-HT₄ receptor agonist prucalopride increases enteric neurogenesis in normal development and after injury. Taken together, the results suggest that despite the lack of resident progenitors in the gut, post-embryonic enteric neurogenesis occurs via gut-extrinsic Schwann cell precursors during development and injury, and is promoted by serotonin receptor agonists. The absence of classical glia in the ENS further suggests that neural crest-derived enteric glia might have evolved after the teleost lineage

Health and Human Rights Education in U.S. Schools of Medicine and Public Health: Current Status and Future Challenges

BACKGROUND: Despite increasing recognition of the importance of human rights in the protection and promotion of health, formal human rights education has been lacking in schools of medicine and public health. Our objectives were: 1) to determine the nature and extent of health and human rights (HHR) education among schools of medicine (SOMs) and public health (SPHs); 2) to identify perceived barriers to implementing HHR curricula; 3) to learn about deans' interests and attitudes toward HHR education, and; 4) to identify factors associated with offering HHR education. METHODS AND PRINCIPAL FINDINGS: We conducted a cross-sectional survey among deans of all accredited allopathic SOMs and SPHs in the United States and Puerto Rico. Seventy-one percent of U.S. SOMs and SPHs responded. Thirty-seven percent of respondents indicated that their schools offered some form of HHR education. Main barriers to offering HHR education included competition for time, lack of qualified instructors and lack of funding. Among schools not offering HHR education, 35% of deans were interested in offering HHR education. Seventy-six percent of all deans believed that it was very important or important to offer HHR education. Multiple regression analysis revealed that deans' attitudes were the most important factor associated with offering any HHR education. CONCLUSION: Findings indicate that though a majority of deans of SOMs and SPHs believe that knowledge about human rights is important in health practice and support the inclusion of HHR studies in their schools, HHR education is lacking at most of their institutions. These results and the growing recognition of the critical interdependence between health and human rights indicate a need for SOMs and SPHs to work towards formal inclusion of HHR studies in their curricula, and that HHR competency requirements be considered to overcome barriers to its inclusion

Exploring Schwann cell precursor-derived enteric neurogenesis in post-embryonic development and regeneration

The enteric nervous system (ENS) is essential for normal gastrointestinal function, and defects in the ENS define several difficult to treat conditions ranging from Hirschsprung disease to esophageal achalasia. While the developmental origin of the ENS from neural crest cells is well understood, there is conflicting evidence regarding postnatal enteric neurogenesis and neuronal homeostasis. Using zebrafish as a model due to its simplified ENS which is amenable to live-imaging, we sought to explore the origin of enteric neurons that arise in post-embryonic life in both normal development and upon injury, and tested effects of the 5HT4 receptor agonist, prucalopride, in this process.To assess for putative resident neuronal precursors, we performed in situ hybridization, immunohistochemistry, and confocal imaging of transgenic lines (live larvae and dissected adult intestine). To detect post-embryonic enteric neurogenesis, we photoconverted enteric neurons within the intestines of a Phox2b-kaede transgenic line such that all resident neurons turned from green to red. We then performed live time-lapse imaging to assess for the emergence of new, green-only neurons. In other experiments, resident enteric neurons were removed using two-photon laser ablation. To follow the potential contribution of neural crest-derived cells to the gut, lineage tracing was performed with neural tube injections of a lipophilic dye as well as with an inducible Sox10-Cre transgenic line. Lastly, post-embryonic zebrafish were exposed to prucalopride to test this drug’s effect on enteric neurogenesis both during normal development and after injury.Our results suggest that the post-embryonic zebrafish intestine lacks resident neurogenic precursors, and indeed appears to have no enteric glia. Despite this, enteric neurogenesis persists post-embryonically both during normal development and after injury. Our data suggest that new enteric neurons arise from trunk neural crest-derived Schwann cell precursors that migrate along nerves to the intestine. Prucalopride increases enteric neurogenesis in normal development as well as after injury if exposure occurs prior to injury. This study provides evidence that SCPs originating from the trunk neural crest mediate this neurogenesis in post-embryonic life and can be pharmacologically manipulated, which could have significant clinical implications for several enteric neuropathies

Case-control study of the association of chronic acid suppression and social determinants of health with COVID-19 infection.

Acid suppressants are widely-used classes of medications linked to increased risks of aerodigestive infections. Prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We aimed to determine the impact of chronic acid suppression use on COVID-19 infection risk while simultaneously evaluating the influence of social determinants of health to validate known and discover novel risk factors. We assessed the association of chronic acid suppression with incident COVID-19 in a 1:1 case-control study of 900 patients tested across three academic medical centers in California, USA. Medical comorbidities and history of chronic acid suppression use were manually extracted from health records by physicians following a pre-specified protocol. Socio-behavioral factors by geomapping publicly-available data to patient zip codes were incorporated. We identified no evidence to support an association between chronic acid suppression and COVID-19 (adjusted odds ratio 1.04, 95% CI 0.92-1.17, P = 0.515). However, several medical and social features were positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new infection. These findings demonstrate the value of integrating publicly-available databases with medical data to identify critical features of communicable diseases