Background: Cardiac development is a dynamic process both temporally and spatially. These complex processes are often disturbed and lead to congenital cardiac anomalies that affect approximately 1% of live births. Disease-causing variants in several genetic loci lead to cardiac anomalies, with variants in transcription factor NKX2-5 gene being one of the largest variants known. Gestational hypoxia, such as seen in high-altitude pregnancy, has been known to affect cardiac development, yet the incidence and underlying mechanisms are largely unknown.Methods and Results: Normal wild-type female mice mated with heterozygous Nkx2-5 mutant males were housed under moderate hypoxia (14% O2) or normoxia (20.9% O2) conditions from 10.5 days of gestation. Wild-type mice exposed to hypoxia demonstrate excessive trabeculation, ventricular septal defects, irregular morphology of interventricular septum as well as atrial septal abnormalities, which overlap with those seen in heterozygous Nkx2-5 mutant mice. Genome-wide transcriptome done by RNA-seq of a 2-day hypoxic exposure on wild-type embryos revealed abnormal transcriptomes, in which approximately 60% share those from Nkx2-5 mutants without hypoxia. Gestational hypoxia reduced the expression of Nkx2-5 proteins in more than one-half along with a reduction in phosphorylation, suggesting that abnormal Nkx2-5 function is a common mechanism shared between genetic and gestational hypoxia-induced cardiac anomalies, at least at a specific developing stage.Conclusion: The results of our study provide insights into a common molecular mechanism underlying non-genetic and genetic cardiac anomalies.
The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women’s health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women’s cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.
Streptococcus pneumoniae, a gram-positive diplococcus, is the most common cause of bacterial pneumonia. The diagnosis of pneumococcal pneumonia is usually confirmed by chest x-ray and gram stain. The most appropriate antibiotics for treatment pneumococcal infection are macrolides, beta-lactams, and quinolones. Two vaccines, PPSV23 and PCV13, are highly effective in preventing infection.
BackgroundMany factors contribute to the decision to provide abortion in the United States. We aim to describe pre-residency experiences and decisions that contribute to choosing a career as an abortion provider in the United States.MethodsWe conducted 60-min semi-structured telephone interviews with 34 current abortion care providers about their career trajectories, decision-making and planning. Interviews were transcribed and coded by three members of the research team using thematic analysis.ResultsA majority of the participants considered (73.5%, n=25) and firmly committed (62.8%, n=22) to providing abortion care prior to entering residency. They described important professional experiences with women’s health and reproductive rights, as well as personal experiences with abortion care, all of which inspired them to seek out abortion training during medical school and residency. Participants also described a dearth of mentors or role models until late in training, especially for family physicians.ConclusionsOur study suggests that the decision to provide abortion care is often made prior to residency training, before or during medical school, so additional support may be needed to promote exposure to abortion care during undergraduate medical education or even before. Further, there is a need for improved mentorship and role modelling during these periods, especially for family physicians. This may be especially critical after the overturn of Roe v Wade, as medical schools in restrictive states may not be able to provide abortions to patients, depriving students of role models who are abortion providers.
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