Background The global COVID-19 pandemic has placed tremendous physical and mental strain on the US healthcare system. Studies examining the effects of outbreaks have demonstrated both an increased prevalence and long-term development of Post-Traumatic Stress Disorder (PTSD) symptoms in healthcare providers. We sought to assess the impact of the COVID-19 pandemic on the psychological well-being of medical providers, medical trainees, and administrators at a large academic center to identify stressors and moderators to guide future mental health and hospital-system interventions. Methods A 42-item survey examining specific stressors, grit, and resilience was widely distributed to physicians, residents, fellows, and administrators a large academic institution for departmental distribution. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value <0.05 was considered statistically significant. Results A total of 785 participants completed the survey. The majority of respondents rated their stress to be significantly increased during the pandemic. Respondents' fear of transmitting the virus to their family members was a significant stressor. Higher resilience was associated with lower stress, anxiety, fatigue, and sleep disturbances. Overall, respondents felt supported by their departments and institution and felt contingency plans and personal protective equipment were adequate. Conclusions Healthcare workers have increased resilience in the face of heightened stress during a pandemic. Higher resilience and grit were protective factors in managing personal and system-level stressors at the peak of the COVID-19 pandemic in our institution. Implementing an intervention designed to enhance healthcare workers’ resilience in response to the COVID-19 pandemic is warranted.

Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5′ insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter the timing of birth.

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Nematodes represent a diverse phylum of both free living and parasitic species. While the species Caenorhabditis elegans (C. elegans) is a valuable model organism, parasitic nematodes or helminths pose a serious threat to human health. Indeed, helminths cause many neglected tropical diseases that afflict humans. Nematode glycoconjugates have been implicated in evasive immunomodulation, a hallmark of nematode infections. One monosaccharide residue present in the glycoconjugates of several human pathogens is galactofuranose (Galf). This five-membered ring isomer of galactose has not been detected in mammals, making Galf metabolic enzymes attractive therapeutic targets. The only known pathway for biosynthetic incorporation of Galf into glycoconjugates depends upon generation of the glycosyl donor UDP-Galf by the flavoenzyme uridine 5’-diphosphate (UDP) galactopyranose mutase (UGM or Glf). A putative UGM encoding gene (glf-1) was recently identified in C. elegans. Because Galf has yet to be identified in any nematode glycan, we sought to assess the catalytic activity of the C. elegans glf-1 gene product (CeUGM). We found that CeUGM catalyzes the isomerization of UDP-Galf and UDP-galactopyranose (UDP-Galp). In the presence of enzyme, substrate, and a hydride source, a galactose–N5-FAD adduct was isolated, suggesting the CeUGM flavin adenine dinucleotide (FAD) cofactor serves as a nucleophile in covalent catalysis. Homology modeling and protein variants indicate that CeUGM possesses an active site similar to that of prokaryotic enzymes, despite the low sequence identity (~15%) between eukaryotic and prokaryotic UGM proteins. Even with the primary sequence differences, heterocyclic UGM inhibitors developed against prokaryotic proteins also inhibit CeUGM activity. We postulate that these inhibitors can serve as chemical probes of Galf in nematodes and as anthelmintic leads. Together, our data suggest that CeUGM facilitates the biosynthetic incorporation of Galf into nematode glycoconjugates through generation of the glycosyl donor UDP-Galf.

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