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IntroductionLittle is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID-19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID-19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID-19-related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties.MethodData were collected in spring 2020, through an anonymous survey delivered to a purposively-selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID-19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample.ResultsThe majority of the sample (52.7%-87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID-19 moral distress: negative impact on family, fear of infecting others, and work-related concerns. All three factors were significantly associated with severity and positive screen for COVID-19-related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes.ConclusionMoral distress is prevalent in FHCWs and includes family-, infection-, and work-related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties.

Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.

The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8(-/-) mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance.