Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression.

Fungal-mediated disease progression and antifungal drug efficacy are significantly impacted by the dynamic infection microenvironment. At the site of infection, oxygen often becomes limiting and induces a hypoxia response in both the fungal pathogen and host cells. The fungal hypoxia response impacts several important aspects of fungal biology that contribute to pathogenesis, virulence, antifungal drug susceptibility, and ultimately infection outcomes. In this review, we summarize recent advances in understanding the molecular mechanisms of the hypoxia response in the most common human fungal pathogens, discuss potential therapeutic opportunities, and highlight important areas for future research.

Deficits in volumetric bone mineral density, bone microarchitecture, and estimated bone strength in women with atypical anorexia nervosa compared to healthy controls.

OBJECTIVE: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. METHOD: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21-46 years. RESULTS: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p < .05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p < .05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high-resolution peripheral quantitative computed tomography (HR-pQCT) variables in atypical anorexia nervosa. DISCUSSION: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR-pQCT variables are associated with increased fracture risk. PUBLIC SIGNIFICANCE: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation.

Recruitment strategies to increase racial and ethnic diversity in anorexia nervosa clinical research.

OBJECTIVE: Inclusion of underrepresented racial and ethnic groups in eating disorder (ED) research is a critical unmet need, but evidence-based recruitment strategies are lacking. We sought to determine whether methods we had implemented to increase recruitment of underrepresented racial and ethnic groups were successful in improving racial and ethnic diversity in a clinical trial in women with anorexia nervosa. METHOD: We implemented new strategies for recruitment of underrepresented racial and ethnic groups in a clinical trial on bone health in women with anorexia nervosa, including leveraging social media, liberalizing language on advertisements to be more inclusive of women who are as yet undiagnosed with the disorder or feel stigmatized by its name, translating advertisements to Spanish, and engaging community health centers. We compared participants' race and ethnicity in this clinical trial versus two similar prior clinical trials. RESULTS: The percent of non-White and Hispanic participants who have signed a consent form in our ongoing clinical trial (2021-2023) is higher versus two previous clinical trials on bone health in women with anorexia nervosa (2011-2019) with similar inclusion/exclusion criteria and endpoints [non-White: 11/38 (28.9%) vs. 11/188 (5.9%), Hispanic: 6/38 (15.8%) vs. 5/188 (2.7%), p ≤ 0.006]. There was no change in the percent of Black participants [0/38 (0%) vs. 1/188 (0.5%), p = 1.0]. DISCUSSION: Viewing clinical research recruitment through a diversity, equity, and inclusion lens can improve racial and ethnic diversity in ED research. Further research recruitment strategies are needed to be more inclusive of Black populations.