ABSTRACT
COVID-19 virus, since the detection of the first case in Wuhan in 2019, has caused a worldwide pandemic with significant human, economic and social costs. Fortunately, several vaccines and treatments, both IV and oral, are currently approved against the COVID-19 virus. Paxlovid is an oral treatment option for patients with mild-to-moderate disease, and it effectively reduces disease severity in high-risk patients. Paxlovid is an oral antiviral that consists of a combination of nirmatrelvir and ritonavi. As an oral medication suitable for outpatient treatment, it reduces the cost, hospitalization and mortality associated with COVID-19 infection. The pregnant population is a high-risk category for COVID-19 disease. Given their exclusion in clinical trials, there is limited data regarding Paxlovid use in pregnant and lactating women. Indirect evidence from ritonavir use as part of HAART therapy in the pregnant and lactating population with HIV has shown no significant teratogenicity. Moreover, animal studies on the use of nirmatrelvir do not suggest teratogenicity. This article summarizes the available data on ritonavir and nirmatrelvir use during pregnancy and in ongoing clinical trials. We also review the recommendations of major societies worldwide regarding Paxlovid use in pregnant and breastfeeding patients.
ABSTRACT
BACKGROUND: On March 11, 2020, the New Mexico Governor declared a public health emergency in response to the COVID-19 pandemic. The New Mexico medical advisory team contacted University of New Mexico (UNM) faculty to form a team to consolidate growing information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease to facilitate New Mexico's pandemic management. Thus, faculty, physicians, staff, graduate students, and medical students created the "UNM Global Health COVID-19 Intelligence Briefing." OBJECTIVE: In this paper, we sought to (1) share how to create an informative briefing to guide public policy and medical practice and manage information overload with rapidly evolving scientific evidence; (2) determine the qualitative usefulness of the briefing to its readers; and (3) determine the qualitative effect this project has had on virtual medical education. METHODS: Microsoft Teams was used for manual and automated capture of COVID-19 articles and composition of briefings. Multilevel triaging saved impactful articles to be reviewed, and priority was placed on randomized controlled studies, meta-analyses, systematic reviews, practice guidelines, and information on health care and policy response to COVID-19. The finalized briefing was disseminated by email, a listserv, and posted on the UNM digital repository. A survey was sent to readers to determine briefing usefulness and whether it led to policy or medical practice changes. Medical students, unable to partake in direct patient care, proposed to the School of Medicine that involvement in the briefing should count as course credit, which was approved. The maintenance of medical student involvement in the briefings as well as this publication was led by medical students. RESULTS: An average of 456 articles were assessed daily. The briefings reached approximately 1000 people by email and listserv directly, with an unknown amount of forwarding. Digital repository tracking showed 5047 downloads across 116 countries as of July 5, 2020. The survey found 108 (95%) of 114 participants gained relevant knowledge, 90 (79%) believed it decreased misinformation, 27 (24%) used the briefing as their primary source of information, and 90 (79%) forwarded it to colleagues. Specific and impactful public policy decisions were informed based on the briefing. Medical students reported that the project allowed them to improve on their scientific literature assessment, stay current on the pandemic, and serve their community. CONCLUSIONS: The COVID-19 briefings succeeded in informing and guiding New Mexico policy and clinical practice. The project received positive feedback from the community and was shown to decrease information burden and misinformation. The virtual platforms allowed for the continuation of medical education. Variability in subject matter expertise was addressed with training, standardized article selection criteria, and collaborative editing led by faculty.
ABSTRACT
NG2-glia are highly proliferative oligodendrocyte precursor cells (OPCs) that are widely distributed throughout the central nervous system (CNS). During development, NG2-glia predominantly differentiate into oligodendrocytes (OLs) to myelinate axon fibers, but they can also remain as OPCs persisting into the mature CNS. Interestingly, NG2-glia in the gray matter (GM) are intrinsically different from those in the white matter (WM) in terms of proliferation, differentiation, gene expression, and electrophysiological properties. Here we investigate the role of the transcriptional regulator, ASCL1, in controlling NG2-glia distribution and development in the GM and WM. In the spinal cord, ASCL1 levels are higher in WM NG2-glia than those in the GM. This differential level of ASCL1 in WM and GM NG2-glia is maintained into adult stages. Long-term clonal lineage analysis reveals that the progeny of single ASCL1+ oligodendrocyte progenitors (OLPs) and NG2-glia are primarily restricted to the GM or WM, even though they undergo extensive proliferation to give rise to large clusters of OLs in the postnatal spinal cord. Conditional deletion of Ascl1 specifically in NG2-glia in the embryonic or adult spinal cord resulted in a significant reduction in the proliferation but not differentiation of these cells. These findings illustrate that ASCL1 is an intrinsic regulator of the proliferative property of NG2-glia in the CNS.
