Identifying Strategies for the Use of Gender and Sex Language in Clinical One-Liners.

Purpose: The "one-liner," commonly used in clinical communications, summarizes a patient's identity, presenting condition, medical history, and clinical findings. Imprecise, inconsistent use of gender and sex information in one-liners threatens the provision of affirming care to transgender, nonbinary, gender-expansive, and intersex patients and may exacerbate health care disparities. This study aimed to generate guidance for communicating gender and sex information in one-liners. Methods: This is an explanatory sequential, equal status mixed methods study of transgender, nonbinary, gender-expansive, and intersex people and clinicians caring for this population. Survey participants rated one-liners on a five-point Likert-type scale of appropriateness, considering affirmation and clinical utility, and provided open-ended comments. We conducted two focus groups with survey respondents to explore survey results and performed a thematic analysis of survey comments and focus group transcripts. Results: Survey respondents included 57 clinicians and 80 nonclinicians. One-liners containing patient pronouns were rated most appropriate, and appropriate patient descriptors included self-described gender identity or gender-neutral terms. In scenarios where patient sex information was not pertinent to the chief concern (CC), one-liners containing no sex information were rated most appropriate. Four themes were identified: inclusion of sex information based on relevance to the CC, accurate patient representation, influence of clinical setting, and risk of harm from inaccurate one-liners. Conclusion: This study generated data to support the appropriate use of gender and sex language in one-liners. Clinicians, educators, and trainees may use these findings to compose one-liners that are affirming and clinically useful for patients of diverse gender and sex identities.

Care across the gender spectrum: A transgender health curriculum in the Obstetrics and Gynecology clerkship.

BACKGROUND: A lack of undergraduate medical curricula on providing healthcare to transgender and gender diverse (TGD) patients has contributed to significant health disparities for TGD communities. To address this gap, we designed and evaluated a novel curriculum to train Obstetrics and Gynecology (OB/GYN) clerkship students in caring for TGD patients. METHODS: Following Kern's 6-step method for curriculum development, we created a two-part curriculum on TGD healthcare topics - an online module on gender-affirming care, followed by a series of interactive cases on TGD-specific health topics. Undergraduate medical students completing their core OB/GYN clerkships at a university academic medical center (January-December 2021) were invited to complete this curriculum. Participants completed pre/post assessment surveys to assess their experience caring for TGD patients, as well as a scored knowledge assessment before and after completing the curriculum. RESULTS: Sixty-five students participated in this curricular assessment. Prior to completing the module, 45% agreed that they had received adequate TGD health training. Following module completion, students reported increased comfort in caring for transgender patients (49.2% vs. 81.5%; p < .001) and endorsed an improved fund of knowledge of both healthcare maintenance for TGD patients (61.5% vs. 100%; p < .001) and gender affirming medical therapies (60.0% vs. 96.9%; p < .001). Knowledge scores increased from a mean of 9.65 (1.81) to 12.5 (2.20) out of 15 (p < .001). In post-assessment surveys, 95% of participants agreed that the module was helpful for their learning. Qualitatively, students suggested longitudinal integration of TGD-topics into the pre-clinical curriculum, and expanded opportunities to practice patient counseling. CONCLUSION: The findings of this study support the need for student education on TGD health. Integration of interactive, case-based TGD-care curricula into clinical training may increase medical students' knowledge and comfort in caring for TGD patients. Ongoing efforts to integrate TGD health training into undergraduate medical student curricula are necessary.

Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice.

Among children with the most severe presentation of Marfan syndrome (MFS), an inherited disorder of connective tissue caused by a deficiency of extracellular fibrillin-1, heart failure is the leading cause of death. Here, we show that, while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function, pressure overload (PO) induces an acute and severe dilated cardiomyopathy in association with fibrosis and myocyte enlargement. Failing MFS hearts show high expression of TGF-ß ligands, with increased TGF-ß signaling in both nonmyocytes and myocytes; pathologic ERK activation is restricted to the nonmyocyte compartment. Informatively, TGF-ß, angiotensin II type 1 receptor (AT1R), or ERK antagonism (with neutralizing antibody, losartan, or MEK inhibitor, respectively) prevents load-induced cardiac decompensation in MFS mice, despite persistent PO. In situ analyses revealed an unanticipated axis of activation in nonmyocytes, with AT1R-dependent ERK activation driving TGF-ß ligand expression that culminates in both autocrine and paracrine overdrive of TGF-ß signaling. The full compensation seen in wild-type mice exposed to mild PO correlates with enhanced deposition of extracellular fibrillin-1. Taken together, these data suggest that fibrillin-1 contributes to cardiac reserve in the face of hemodynamic stress, critically implicate nonmyocytes in disease pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac decompensation.

In Vivo Hepatic Reprogramming of Myofibroblasts with AAV Vectors as a Therapeutic Strategy for Liver Fibrosis.

Liver fibrosis, a form of scarring, develops in chronic liver diseases when hepatocyte regeneration cannot compensate for hepatocyte death. Initially, collagen produced by myofibroblasts (MFs) functions to maintain the integrity of the liver, but excessive collagen accumulation suppresses residual hepatocyte function, leading to liver failure. As a strategy to generate new hepatocytes and limit collagen deposition in the chronically injured liver, we developed in vivo reprogramming of MFs into hepatocytes using adeno-associated virus (AAV) vectors expressing hepatic transcription factors. We first identified the AAV6 capsid as effective in transducing MFs in a mouse model of liver fibrosis. We then showed in lineage-tracing mice that AAV6 vector-mediated in vivo hepatic reprogramming of MFs generates hepatocytes that replicate function and proliferation of primary hepatocytes, and reduces liver fibrosis. Because AAV vectors are already used for liver-directed human gene therapy, our strategy has potential for clinical translation into a therapy for liver fibrosis.

AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites.

Malaria, caused by protozoan Plasmodium parasites, remains a prevalent infectious human disease due to the lack of an efficient and safe vaccine. This is directly related to the persisting gaps in our understanding of the parasite's interactions with the infected host, especially during the clinically silent yet essential liver stage of Plasmodium development. Previously, we and others showed that genetically attenuated parasites (GAP) that arrest in the liver induce sterile immunity, but only upon multiple administrations. Here, we comprehensively studied hepatic gene and miRNA expression in GAP-injected mice, and found both a broad activation of IFNγ-associated pathways and a significant increase of murine microRNA-155 (miR-155), that was especially pronounced in non-parenchymal cells including liver-resident macrophages (Kupffer cells). Remarkably, ectopic upregulation of this miRNA in the liver of mice using robust hepatotropic adeno-associated virus 8 (AAV8) vectors enhanced GAP's protective capacity substantially. In turn, this AAV8-mediated miR-155 expression permitted a reduction of GAP injections needed to achieve complete protection against infectious parasite challenge from previously three to only one. Our study highlights a crucial role of mammalian miRNAs in Plasmodium liver infection in vivo and concurrently implies their great potential as future immune-augmenting agents in improved vaccination regimes against malaria and other diseases.