HSP72 is a stress-inducible chaperone whose decline drives age- and obesity-related metabolic dysfunction. While increasing skeletal muscle HSP72 benefits males metabolically, its regulatory role in females remains largely unexplored. Using a whole-body HSP72 knockout (KO) mouse model, we uncovered striking sexual dimorphism in metabolic homeostasis and mitochondrial dynamics. In males, HSP72 KO drove metabolic deterioration, marked by increased adiposity, insulin resistance, corresponding with mitochondrial dysfunction and hyperfusion. Conversely, female KOs exhibited a protective phenotype, demonstrating reduced gonadal adiposity, enhanced insulin sensitivity, increased VO2, and elevated voluntary physical activity versus wild-type controls. Female KO skeletal muscle mitochondria shifted toward enhanced fission—yielding smaller, spherical organelles—coupled with increased electron transport chain activity. Mechanistically, this female-specific adaptation mirrored the metabolic profile of muscle-targeted estrogen receptor alpha (ERα) overexpression. We found that HSP72 ablation in females triggered a compensatory upregulation of muscle ERα—a molecular defense entirely absent in males. Our findings unmask a sexual dimorphism in chaperone biology, establishing that female metabolic protection in the absence of HSP72 relies on enhanced ERα signaling. This work emphasizes the vital need to integrate sex as a fundamental biological variable when developing metabolism-modulating therapeutics.

This abstract has been withheld from publication.

Uveitis is an inflammatory eye disease associated with autoimmune conditions and infections, and remains a leading cause of preventable vision loss. Clinical assessment of anterior chamber (AC) inflammation relies on the Standardized Uveitis Nomenclature (SUN) grading system, which, while widely used, is subjective and prone to inter-clinician variability. Recent work has shown that swept-source anterior segment optical coherence tomography (SS AS-OCT) combined with automated cell counting can improve sensitivity and detect subclinical inflammation beyond clinical exam. However, existing approaches are limited by reduced performance in non-phakic eyes and the absence of integrated quality control. To address these limitations, we developed an interpretable deep learning algorithm for automated AC cell detection. The model performs simultaneous evaluation of scan quality, phakic status, and imaging artifacts in a single forward pass before cell localization. Our dataset includes phakic, pseudophakic, and aphakic SS AS-OCT scans, with quality control established through multi-grader manual cell counting across scan types. Preliminary findings demonstrate improved consistency and generalizability compared to current automated methods, particularly in non-phakic eyes. Ongoing work focuses on validating model performance against SUN grading to develop a more accurate and objective tool for monitoring uveitic inflammation.

Introduction and Hypotheses: Neovascularization is essential in cardiac ischemic damage repair. Our laboratory has observed that 3D organoid culture induces a mesenchymal-to-endothelial transition (MEndT), a novel neovascularization process, in human coronary artery smooth muscle cells (hCASMCs). We hypothesize that NOTCH plays an important role in hCASMC MEndT. Methods: hCASMCs were cultured in 3D hanging drops to form organoids. NOTCH was inhibited in this system by treating with DAPT. Effects of NOTCH inhibition were assessed by measuring EC-associated gene transcription using qPCR and quantifying sprouting behavior in fibrin gel. Results/Discussion: DAPT significantly decreased EC-associated gene expression compared to vehicle controls, suggesting NOTCH is essential for MEndT. vWF showed an unexpected increase in expression despite NOTCH inhibition, indicating possible incomplete inhibition or stimulation of a NOTCH-independent pathway. Initial findings support the role of NOTCH in 3D organoid culture-induced MEndT in hCASMCs. Future research will define which NOTCH isoform (NOTCH1-3) is responsible for the MEndT process in hCASMCs. This study is significant because it provides first insights into the mechanisms of MEndT in vascular smooth muscle cells, which could lead to new strategies for vascular regeneration.

Fluid status assessment is a challenging yet essential aspect of removing fluid from patients undergoing hemodialysis (HD), as both excessive and insufficient fluid removal can worsen clinical outcomes. Standard approaches involving Crit-line monitoring, point-of-care ultrasound, patient-reported symptoms, and physical examination (e.g., checking for edema) remain imprecise and time-intensive for doctors to properly diagnose and treat. Bioimpedance analysis (BIA) is a novel, non-invasive method that uses electrical currents to analyze body composition and evaluate fluid status. While BIA is widely used in obesity clinics and fitness programs, it remains underutilized for dialysis patients. At the West Los Angeles Veterans Affairs Medical Center, this project evaluated whether portable BIA could serve as a time-efficient alternative for dialysis optimization. Patients were categorized as hypovolemic, euvolemic, or hypervolemic using both BIA and traditional clinical assessment, and agreement was analyzed with weighted kappa statistics. Preliminary comparison of clinical judgment and BIA showed fair agreement (kappa = 0.397, 95% CI 0.067-0.725). Discordant cases suggest that BIA may not account for physiological tolerance among dialysis patients, highlighting the need for further calibration or combined methodologies. With these results in mind, our nephrology division established a new dialysis quality improvement initiative with the goal of expanding applied BIA into an IRB-approved study and further optimizing HD treatment.