Faculty Bibliography

Through a review of current research, standards of care, and best practices, this paper serves as a resource for emergency physicians (EPs) caring for persons who identify as transgender and gender diverse (T/GD) in the emergency department (ED). Both patient- and physician-based research have identified existent potential knowledge gaps for EPs caring for T/GD in the ED. T/GD have negative experiences related to their gender identity when seeking emergency medical care and may even delay emergency care for fear of discrimination. Through the lens of cultural humility, this paper aims to address potential knowledge gaps for EPs, identify and reduce barriers to care, highlight gender-affirming hospital policies and protocols, and improve the care and experience of T/GD in the ED.

The emergency department serves as a critical access point to the health system for many patients, especially those with limited resources. Screening for disease or risk factors for poor health outcomes can potentially improve both individual and population health. Screening initiatives should focus on evidence-based strategies and take local epidemiology and ED capacity into consideration. Initiatives should strive for community support and transparency with patients. They should also be financially sustainable for those involved. Screening can identify patients who can then be counseled, provided with prophylaxis or treatment, or referred to external resources. Through screening and intervention, the ED can serve as a vital contributor to individual and population health.

BACKGROUND:Thymic epithelial cell (TEC) microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus. METHODOLOGY/PRINCIPAL FINDINGS/RESULTS:Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+) Foxn1(+) and Aire(+) TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments. CONCLUSIONS/SIGNIFICANCE/CONCLUSIONS:Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic degeneration associated with cancer therapy and bone marrow transplants.