Fetal lung underdevelopment, also known as pulmonary hypoplasia, is characterized by decreased lung growth and maturation. The most common birth defect found in babies with pulmonary hypoplasia is congenital diaphragmatic hernia (CDH). Despite research and clinical advances, babies with CDH still have high morbidity and mortality rates, which are directly related to the severity of lung underdevelopment. To date, there is no effective treatment that promotes fetal lung growth and maturation. Here, we describe a stem cell–based approach in rodents that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). Using fetal rodent models of pulmonary hypoplasia (primary epithelial cells, organoids, explants, and in vivo), we demonstrated that AFSC-EV administration promoted branching morphogenesis and alveolarization, rescued tissue homeostasis, and stimulated epithelial cell and fibroblast differentiation. We confirmed this regenerative ability in in vitro models of lung injury using human material, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. Investigating EV mechanism of action, we found that AFSC-EV beneficial effects were exerted via the release of RNA cargo. MicroRNAs regulating the expression of genes involved in lung development, such as the miR17–92 cluster and its paralogs, were highly enriched in AFSC-EVs and were increased in AFSC-EV–treated primary lung epithelial cells compared to untreated cells. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application in patients with pulmonary hypoplasia.
Coronavirus disease 2019 (COVID-19) infections can cause many complications, including central nervous system (CNS) complications. One of the most common COVID-19 CNS complications is COVID-19 encephalopathy, a disorder characterized by cognitive impairment, altered consciousness, and even seizures. The Moderna COVID-19 vaccine is a recently approved mRNA-based vaccine aimed at preventing COVID-19 infections and their complications. Here, we describe two patients with no known neurological or psychiatric history who presented with encephalopathy and seizures that began after part one of their Moderna COVID-19 vaccine series. To our knowledge, there are no other reports of post-Moderna COVID-19 vaccine encephalopathy in the literature. We suggest a mechanism for this complication and thoroughly discuss why the Moderna vaccine is possibly responsible, by addressing confounders in our patients.
is currently a 2nd year medical student at the Medical College of Wisconsin in Milwaukee, USA of a 4-year MD program. He is currently in the middle of studying for the Step 1 medical licensing exam.
Background: Around 10% of Americans meet the Rome IV criteria for functional dyspepsia (FD), with a significantly higher rate in women. FD also has a higher prevalence in women below the age of 50, suggesting that women who are affected are likely to be of reproductive age. Unfortunately, there is a lack of research or evidence-based guidelines on managing FD in pregnancy.
Aims and Methods:To address this issue, we aimed to perform a systematic review of the interactions between FD and pregnancy and managing pre-existing FD in the peripartum and post-partum phases using current lifestyle, pharmacological, nonpharmacological and alternative medicine interventions. Results: Due to the lack of Rome IV FD-specific data in pregnancy, we instead performed a narrative review on how existing FD interventions could be extrapolated to the pregnant population. Where possible we use the highest level of available evidence or official guidelines to answer these questions, which often involves synthesising treatment and safety evidence of these interventions in other diseases during pregnancy. Finally, we highlight current substantial knowledge gaps requiring further research for the safe management of a pregnant patient with pre-existing FD. Conclusions: Overall, despite the paucity of knowledge of treating FD during pregnancy, providers can mitigate this uncertainty by planning ahead with the patient. Patients should ideally minimise treatment until after breastfeeding. However, interdisciplinary resources are available to ensure that minimal-risk interventions are maximised, while interventions with more risks, if necessary, are justifiable by both the patient and the care team. Future investigations should continue to elicit the mechanistic relationship between FD and pregnancy while cautiously expanding prospective research on promising and safe therapies in pregnant patients with preexisting FD.
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