Intersectional Model of Service Use: Understanding Transgender and Nonbinary Healthcare Access

Transgender and nonbinary (TNB) people often have difficulty accessing healthcare services because of the systemic forces of transphobia and cisgenderism. Despite this, there is little theory specifically designed to examine healthcare access among TNB people. We conducted a literature review to identify studies examining TNB healthcare access. We screened a total of 2,050 unique articles for inclusion, resulting in a final sample of 46 articles that met the review criteria. Theories used and key findings were coded to inform the development of the Intersectional Model of Service Use (IMSU) for TNB people. The IMSU builds upon current theoretical frameworks including the Behavioral Model for Vulnerable Populations (BMVP), which proposes that predisposing, enabling, and need factors drive healthcare utilization among vulnerable populations. The IMSU combines the predisposing, enabling, and need factors of the BMVP with TNB-specific healthcare access factors identified through this integrative review. The findings from this review suggest its effectiveness in informing research and interventions aimed at improving healthcare access among TNB people

Exploring the Experiences of Transgender and Gender Diverse Adults in Accessing a Trans Knowledgeable Primary Care Physician

Transgender and gender diverse individuals face a variety of barriers when attempting to access healthcare, from discrimination to lack of access to lack of knowledgeable providers. Using data from the 2015 United States Trans Survey (N = 27,715), this study looks at the differences within the TGD population regarding having seen a doctor in the past year, having a primary care provider, and having a primary care provider who is knowledgeable about trans health. Logistic regressions indicate that even within an all transgender and gender diverse sample, a variety of identities and experiences are related to increased or decreased likelihood of each of these outcomes, with significant differences across gender, race/ethnicity, age, sexual orientation, disability status, educational attainment, annual income, disability status, religiosity, military status, overall health, housing status, and insurance coverage. Not only should there be an effort to support transgender and gender diverse individuals in accessing care, but there is a clearly indicated need for additional education for healthcare providers, especially those doing primary care, on how to offer knowledgeable, affirming, and intersectional care to their patients

“We Are Doing the Absolute Most That We Can, and No One Is Listening”: Barriers and Facilitators to Health Literacy Within Transgender and Nonbinary Communities

Transgender and nonbinary (TNB) individuals face disparities in nearly every aspect of health. One factor associated with poor health outcomes in other marginalized populations is health literacy, yet no identified studies examine health literacy in TNB samples. Moreover, most health literacy frameworks focus primarily on the capacities of individual patients to understand and use healthcare information, with little attention given to provider literacy and environmental factors. In partnership with a statewide LGBTQ advocacy organization, we recruited 46 transgender and nonbinary individuals to participate in seven focus groups conducted in urban, suburban, and rural locations throughout Colorado. TNB participants consistently engaged in efforts to increase their own health literacy and that of their medical providers yet faced multiple barriers to improve care. Difficulty identifying and physically reaching care, insurance and out-of-pocket expenses, negative experiences with healthcare providers and staff, provider incompetence, discriminatory and oppressive practices, and exclusionary forms and processes emerged as barriers to enacted health literacy among participants. Conversely, facilitators of enacted healthcare literacy included positive experiences with healthcare providers and staff, and inclusive forms and processe

The bioenergetic “CK Clamp” technique detects substrate-specific changes in mitochondrial respiration and membrane potential during early VML injury pathology

Volumetric muscle loss (VML) injuries are characterized by non-recoverable loss of tissue resulting in contractile and metabolic dysfunction. The characterization of metabolic dysfunction in volumetric muscle loss-injured muscle has been interpreted from permeabilized myofiber respiration experiments involving saturating ADP levels and non-physiologic ATP:ADP concentration ratios. The extent to which this testing condition obscures the analysis of mitochondrial (dys) function after volumetric muscle loss injury is unclear. An alternative approach is described that leverages the enzymatic reaction of creatine kinase and phosphocreatine to assess mitochondrial respiration and membrane potential at clamped physiologic ATP:ADP ratios, “CK Clamp.” The objective of this study was to validate the CK Clamp in volumetric muscle loss-injured muscle and to detect differences that may exist between volumetric muscle loss-injured and uninjured muscles at 1, 3, 5, 7, 10, and 14 days post-injury. Volumetric muscle loss-injured muscle maintains bioenergetic features of the CK Clamp approach, i.e., mitochondrial respiration rate (JO2) titters down and mitochondrial membrane potential is more polarized with increasing ATP:ADP ratios. Pyruvate/malate/succinate-supported JO2 was significantly less in volumetric muscle loss-injured muscle at all timepoints compared to uninjured controls (−26% to −84%, p < 0.001) and electron conductance was less at day 1 (−60%), 5 (−52%), 7 (−35%), 10 (−59%), and 14 (−41%) (p < 0.001). Palmitoyl-carnitine/malate-supported JO2 and electron conductance were less affected following volumetric muscle loss injury. volumetric muscle loss-injury also corresponded with a more polarized mitochondrial membrane potential across the clamped ATP:ADP ratios at day 1 and 10 (pyruvate and palmitoyl-carnitine, respectively) (+5%, p < 0.001). This study supports previous characterizations of metabolic dysfunction and validates the CK Clamp as a tool to investigate bioenergetics in traumatically-injured muscle

Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy

Tissue mass-normalized values of cytochrome C reduced in vitro by succinate dehydrogenase from homogenized TAs of VEH- or RAPA-treated LC and KO mice. Two-way ANOVA. (PDF 291 kb

“How Do I Exist in This Body…That’s Outside of the Norm?” Trans and Nonbinary Experiences of Conformity, Coping, and Connection in Atypical Anorexia

Addressing eating disorders (EDs) within trans and nonbinary (TNB) populations is a growing concern, as TNB individuals are two to four times more likely to experience EDs than cisgender women. This study explored the lived experiences of TNB people with atypical anorexia by examining how gender identity impacted experiences of ED illness and (potential) recovery. Nine TNB adults with atypical anorexia were followed for one year and completed semi-structured, in-depth, longitudinal qualitative interviews at baseline, 6 months, and 12 months. Interviews were coded using Braun and Clark’s thematic analysis procedures. Four themes, along with subthemes, emerged regarding the intersection of gender identity and ED experiences: (1) Conforming, (2) Coping, (3) Connecting, and (4) Critiquing. In Conforming, participants highlighted how societal pressures around gender contributed to ED vulnerability. In Coping, participants explained that their EDs represented attempts to cope with the overlapping influences of body dissatisfaction, gender dysphoria, and body disconnection. In Connecting, participants described ED recovery as a process of connecting to self, others, and communities that welcomed and affirmed their diverse identities. In Critiquing, participants described how current ED treatment settings were often unwelcoming of or unprepared for non-cisgender patients. Overall, participants viewed their EDs as intricately linked to their gender identity and experiences of social pressure and discrimination. This study suggests the need for targeted ED prevention and intervention efforts within TNB communities, and the ethical imperative to meaningfully address the needs of TNB patients in ED treatment settings

The RNA-binding protein Msi2 regulates autophagy during myogenic differentiation

Skeletal muscle development is a highly ordered process orchestrated transcriptionally by the myogenic regulatory factors. However, the downstream molecular mechanisms of myogenic regulatory factor functions in myogenesis are not fully understood. Here, we identified the RNA-binding protein Musashi2 (Msi2) as a myogenin target gene and a post-transcriptional regulator of myoblast differentiation. Msi2 knockdown in murine myoblasts blocked differentiation without affecting the expression of MyoD or myogenin. Msi2 overexpression was also sufficient to promote myoblast differentiation and myocyte fusion. Msi2 loss attenuated autophagosome formation via down-regulation of the autophagic protein MAPL1LC3/ATG8 (LC3) at the early phase of myoblast differentiation. Moreover, forced activation of autophagy effectively suppressed the differentiation defects incurred by Msi2 loss. Consistent with its functions in myoblasts in vitro, mice deficient for Msi2 exhibited smaller limb skeletal muscles, poorer exercise performance, and muscle fiber-type switching in vivo. Collectively, our study demonstrates that Msi2 is a novel regulator of mammalian myogenesis and establishes a new functional link between muscular development and autophagy regulation

The RNA-binding protein Msi2 regulates autophagy during myogenic differentiation

Skeletal muscle development is a highly ordered process orchestrated transcriptionally by the myogenic regulatory factors. However, the downstream molecular mechanisms of myogenic regulatory factor functions in myogenesis are not fully understood. Here, we identified the RNA-binding protein Musashi2 (Msi2) as a myogenin target gene and a post-transcriptional regulator of myoblast differentiation. Msi2 knockdown in murine myoblasts blocked differentiation without affecting the expression of MyoD or myogenin. Msi2 overexpression was also sufficient to promote myoblast differentiation and myocyte fusion. Msi2 loss attenuated autophagosome formation via down-regulation of the autophagic protein MAPL1LC3/ATG8 (LC3) at the early phase of myoblast differentiation. Moreover, forced activation of autophagy effectively suppressed the differentiation defects incurred by Msi2 loss. Consistent with its functions in myoblasts in vitro, mice deficient for Msi2 exhibited smaller limb skeletal muscles, poorer exercise performance, and muscle fiber–type switching in vivo. Collectively, our study demonstrates that Msi2 is a novel regulator of mammalian myogenesis and establishes a new functional link between muscular development and autophagy regulation

Developing, Refining, and Testing the Intersectional Model of Service Use: A Transgender and Nonbinary-Specific Model of Healthcare Access

Transgender and nonbinary (TNB) people are more likely to experience negative health outcomes than cisgender (i.e., not TNB) people, but less likely to access healthcare services due to the systemic forces of transphobia and cisgenderism. Despite this, there are few theoretical models of healthcare access specifically designed for TNB people. This three-paper dissertation addresses this gap by developing, refining, and testing the Intersectional Model of Service Use (IMSU), a population-specific framework for researching TNB healthcare access. Manuscript one describes how the initial IMSU was developed from an integrative review of currently available TNB healthcare access literature. This initial IMSU was then revised in manuscript two using qualitative data collected in nine focus group held across the state of Colorado. The revised IMSU was then quantitatively tested in manuscript three using hierarchical logistic regression analyses. Results from manuscript three indicated that the inclusion of TNB-specific healthcare access factors of the IMSU significantly improved its ability to account for healthcare access variance. Specific factors that were significantly associated with healthcare access included self-reporting a disability, sexual orientation, income, the length of time participates needed to wait to access transition-related healthcare, and whether or not participants had changed their gender marker on state-issued identification

TAT-μUtrophin mitigates the pathophysiology of dystrophin and utrophin double-knockout mice

Previously, we demonstrated functional substitution of dystrophin by TAT-μUtrophin (TAT-μUtr) in dystrophin-deficient mdx mice. Herein, we addressed whether TAT-μUtr could improve the phenotype of dystrophin and utrophin double-knockout (mdx:utr−/−) mice. Specifically, we quantitatively compared survival and quality of life assessments in mdx:utr−/− mice receiving TAT-μUtr protein administration against placebo-treated mdx:utr−/− mice (PBS). Additionally, skeletal muscles from TAT-μUtr and PBS mice were tested in vivo and ex vivo for strength and susceptibility to eccentric contraction-induced injury. We found the TAT-μUtr treatment extended life span 45% compared with mice administered PBS. This was attributed to significantly increased food consumption (3.1 vs. 1.8 g/24 h) due to improved ability to search for food as daily cage activities were greater in TAT-μUtr mice (e.g., 364 vs. 201 m ambulation/24 h). The extensor digitorum longus muscles of TAT-μUtr-treated double-knockout mice also displayed increased force-generating capacity ex vivo (8.3 vs. 6.4 N/cm2) and decreased susceptibility to injury ex vivo and in vivo. These data indicate that the functional benefits of TAT-μUtr replacement treatment extend to the mdx:utr−/− double-knockout mouse and support its development as a therapy to mitigate muscle weakness in patients with Duchenne muscular dystrophy