Clinical and sociodemographic characteristics as predictors for quality of life in transmasculine and transfeminine individuals receiving gender-affirming hormone therapy.

Healthcare systems and providers have increasingly acknowledged the role and impact of social determinants in overall health. However, gender-diverse individuals face persistent health disparities due to their identities. There is limited research on the impact of clinical and sociodemographic characteristics on mood and quality of life (QoL) for transgender (TG) individuals. Our study aims to understand and better elucidate social and clinical characteristics of transmasculine (TM) and transfeminine (TF) individuals and their impact on quality of life and depressive symptoms. In this cross-sectional study, 298 TF and TM individuals on gender-affirming hormone therapy (GAHT) were surveyed about their demographic characteristics (age, gender identity, body mass index (BMI), and education), social needs, mood, and quality of life. Multivariable regression modelling was performed to assess the effect of each variable listed above on three domains of QoL (psychological, environmental, and physical) as well as depressive symptoms. We find that QoL scores are similar between TM and TF individuals, with scores in the psychological domain particularly low in both cohorts. TM individuals report higher rates of stress and restroom avoidance than TF individuals. In particular, psychological well-being (measured by the psychological domain of QoL and depressive symptoms) is significantly associated with increased BMI, financial instability, and stress in TM individuals while for TF individuals, psychological well-being is associated with stress and social integration. These data suggest that social circumstances are key drivers of QoL and psychological well-being among gender-diverse individuals receiving GAHT with specific differences between TF and TM individuals. This information may be utilized by healthcare providers and policymakers to address and improve clinical care and social policies to improve health equity for gender-diverse individuals.

Follow-Up of Patients After Total Pancreatectomy and Islet Cell Autotransplantation at Off-Site Islet Isolation Facility.

CONTEXT: Total pancreatectomy with islet autotransplantation (TPIAT) is a definitive management for intractable pain in patients with chronic pancreatitis (CP). Islet autotransplantation (IAT) allows for the preservation of beta cells to prevent complications of long-term diabetes. OBJECTIVE: Our study follows TPIAT recipients for up to 12 years to determine the efficacy of the procedure completed with an off-site islet isolation facility. METHODS: Patient demographics, mixed meal tolerance test measures, glycosylated hemoglobin, insulin requirements, and homeostatic model assessment for insulin resistance values were collected prior to surgery and at the most recent follow-up assessment. RESULTS: Forty-four patients (median age, 46.0 years; range, 20-78 years) underwent TPIAT for CP. At an overall median follow-up time of 845.5 days (range, 195-4470 days) 8 patients were insulin independent and 36 patients were insulin dependent. At the most recent follow-up time point, islet yield per kilogram was the strongest indicator of insulin independence. Homeostatic model assessment for insulin resistance values were comparable between insulin independent and dependent cohorts. CONCLUSIONS: Our long-term follow-up data suggest that IAT can effectively reduce insulin requirements and improve postoperative glycemic control.

Activation of the Medial Prefrontal Cortex Reverses Cognitive and Respiratory Symptoms in a Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2; Amir et al., 1999), a transcriptional regulatory protein (Klose et al., 2005). Mouse models of RTT (Mecp2 mutants) exhibit excitatory hypoconnectivity in the medial prefrontal cortex (mPFC; Sceniak et al., 2015), a region critical for functions that are abnormal in RTT patients, ranging from learning and memory to regulation of visceral homeostasis (Riga et al., 2014). The present study was designed to test the hypothesis that increasing the activity of mPFC pyramidal neurons in heterozygous female Mecp2 mutants (Hets) would ameliorate RTT-like symptoms, including deficits in respiratory control and long-term retrieval of auditory conditioned fear. Selective activation of mPFC pyramidal neurons in adult animals was achieved by bilateral infection with an AAV8 vector expressing excitatory hm3D(Gq) DREADD (Designer Receptors Exclusively Activated by Designer Drugs) (Armbruster et al., 2007) under the control of the CamKIIa promoter. DREADD activation in Mecp2 Hets completely restored long-term retrieval of auditory conditioned fear, eliminated respiratory apneas, and reduced respiratory frequency variability to wild-type (Wt) levels. Reversal of respiratory symptoms following mPFC activation was associated with normalization of Fos protein levels, a marker of neuronal activity, in a subset of brainstem respiratory neurons. Thus, despite reduced levels of MeCP2 and severe neurological deficits, mPFC circuits in Het mice are sufficiently intact to generate normal behavioral output when pyramidal cell activity is increased. These findings highlight the contribution of mPFC hypofunction to the pathophysiology of RTT and raise the possibility that selective activation of cortical regions such as the mPFC could provide therapeutic benefit to RTT patients.