Renal fluid and acid/base balance during refeeding in restrictive eating disorders.

BACKGROUND AND OBJECTIVES: Fluid shifts have been ascribed to central diabetes insipidus in patients with anorexia nervosa hospitalized for refeeding. Recent data, however, suggest that vasopressin production is not dysregulated in this population. Our objective was to describe the trajectory of fluid imbalances in relationship to kidney function, electrolyte disturbances, and acid/base balance during refeeding. METHODS: A retrospective review of daily fluid balance and biochemical values was performed in 70 sequential unique patients admitted to University of California at Los Angeles Hospital Medical Stabilization Program for Eating Disorders from December 2018 to November 2020. RESULTS: Participants (2 males/68 females) were between 10 and 24 years of age and with a median body mass index of 16.1 (14.3, 18.1) kg/m2 . A severe negative fluid balance (>-900 ml/day) was observed in 80% of patients at some point during hospitalization. Serum sodium concentrations were normal on admission and remained stable during refeeding. Serum bicarbonate concentrations were 25 ± 1 mEq/dl on admission and increased above the normal range in 31% of patients. Metabolic alkalosis was inversely associated with the development of a negative fluid balance. Estimated glomerular filtration rate was impaired in 54% of patients, improved with refeeding, and was not associated with the development of a severe negative fluid balance or metabolic alkalosis. DISCUSSION: Chronic energy deprivation alters the physiology of renal fluid and bicarbonate handling in ways that are independent of vasopressin and glomerular filtration. Further studies are warranted to understand the renal adaptations that occur during energy restriction and subsequent refeeding. PUBLIC SIGNIFICANCE: Massive urinary fluid losses occur in patients with restrictive eating disorders hospitalized for refeeding. In addition, many patients have impaired renal bicarbonate excretion. These findings suggest that chronic energy deprivation impairs the kidney's ability to handle the shifts in fluid and acid/base balance that occur when appropriate oral nutrition is re-introduced.

The TROLLEY Study: assessing travel, health, and equity impacts of a new light rail transit investment during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic disrupted life in extraordinary ways impacting health and daily mobility. Public transit provides a strategy to improve individual and population health through increased active travel and reduced vehicle dependency, while ensuring equitable access to jobs, healthcare, education, and mitigating climate change. However, health safety concerns during the COVID-19 pandemic eroded ridership, which could have longstanding negative consequences. Research is needed to understand how mobility and health change as the pandemic recedes and how transit investments impact health and equity outcomes. METHODS: The TROLLEY (TRansit Opportunities for HeaLth, Livability, Exercise and EquitY) study will prospectively investigate a diverse cohort of university employees after the opening of a new light rail transit (LRT) line and the easing of campus COVID-19 restrictions. Participants are current staff who live either < 1 mile, 1-2 miles, or > 2 miles from LRT, with equal distribution across economic and racial/ethnic strata. The primary aim is to assess change in physical activity, travel mode, and vehicle miles travelled using accelerometer and GPS devices. Equity outcomes include household transportation and health-related expenditures. Change in health outcomes, including depressive symptoms, stress, quality of life, body mass index and behavior change constructs related to transit use will be assessed via self-report. Pre-pandemic variables will be retrospectively collected. Participants will be measured at 3 times over 2 years of follow up. Longitudinal changes in outcomes will be assessed using multilevel mixed effects models. Analyses will evaluate whether proximity to LRT, sociodemographic, and environmental factors modify change in outcomes over time. DISCUSSION: The TROLLEY study will utilize rigorous methods to advance our understanding of health, well-being, and equity-oriented outcomes of new LRT infrastructure through the COVID-19 recovery period, in a sample of demographically diverse adult workers whose employment location is accessed by new transit. Results will inform land use, transportation and health investments, and workplace interventions. Findings have the potential to elevate LRT as a public health priority and provide insight on how to ensure public transit meets the needs of vulnerable users and is more resilient in the face of future health pandemics. TRIAL REGISTRATION: The TROLLEY study was registered at ClinicalTrials.gov ( NCT04940481 ) June 17, 2021, and OSF Registries ( https://doi.org/10.17605/OSF.IO/PGEHU ) June 24, 2021, prior to participant enrollment.

Long-term outcomes with oral therapy in liver transplant recipients with hepatitis B.

BACKGROUND: The long-term impact of oral hepatitis B antiviral therapy in liver transplant (LT) recipients is currently underexplored. The objective of this study was to evaluate how oral antiviral agents impact long-term renal function in this population. METHODS: We studied 79 patients who received a LT for hepatitis B and were placed on all-oral antiviral therapy after withdrawing from hepatitis B immune globulin therapy at the University of California, Los Angeles. Laboratory data were obtained through a retrospective chart review. Univariate analysis and two-sided t tests were performed. RESULTS: The mean (±SD [standard deviation]) age at the time of LT was 65.4 (± 8.2) years. The overall mean (±SD) follow-up from LT was 6.5 (±3.3) years. 22.8% (18/79) of recipients on all-oral therapy had worsening of their chronic kidney disease stage, and 17.7% (14/79) had an increase in creatinine of at least 0.3 mg/dL. There were no significant changes in creatinine and GFR in patients while on tenofovir alafenamide. Patient survival was decreased for recipients who developed detectable HBsAg. CONCLUSION: Tenofovir alafenamide appears to have less of an impact on renal function in LT recipients than other antiviral agents. HBV recurrence after transplant is associated with decreased patient survival and remains an important issue to address for LT recipients on oral antiviral therapy.

Cannabinoid-induced changes in the immune system: The role of microRNAs.

Naturally occurring cannabinoids have been used by humans for their medicinal benefits for over several millennia. While the use of cannabinoids has been strictly regulated in the past century, easing of state regulations has been associated with an increase in use of cannabinoids in the United States. The potential therapeutic applications of cannabinoids have been explored and the anti-inflammatory effect of cannabis-derived cannabinoids has been well-documented. The pharmacological effects of cannabinoids are governed by the modulation of cannabinoid receptors, CB1 and CB2, expressed in the central and peripheral tissues. Moreover, growing scientific evidence suggests that the cannabinoid-mediated changes in the immune system involves change in expression of microRNAs (miRNAs). MiRNAs are short non-coding, single-stranded RNA which have the ability to affect post-translational regulation of gene expression. Studies over the past decade have investigated the changes in expression of miRNAs following treatment of various components of the immune system with different chemical modulators of the cannabinoid receptors. Such studies have highlighted the key role played by various miRNAs in driving the observed immunomodulatory effects of cannabinoids. The aim of this review article, therefore, is to summarize the role of miRNAs behind the observed effects of cannabinoids on the overall immune system, rather than focusing on a single disease state.

A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier.

Metastases largely rely on hematogenous dissemination of tumor cells via the vascular system and significantly limit prognosis of patients with solid tumors. To colonize distant sites, circulating tumor cells must destabilize the endothelial barrier and transmigrate across the vessel wall. Here we performed a high-content screen to identify drugs that block tumor cell extravasation by testing 3,520 compounds on a transendothelial invasion coculture assay. Hits were further characterized and validated using a series of in vitro assays, a zebrafish model enabling three-dimensional (3D) visualization of tumor cell extravasation, and mouse models of lung metastasis. The initial screen advanced 38 compounds as potential hits, of which, four compounds enhanced endothelial barrier stability while concurrently suppressing tumor cell motility. Two compounds niclosamide and forskolin significantly reduced tumor cell extravasation in zebrafish, and niclosamide drastically impaired metastasis in mice. Because niclosamide had not previously been linked with effects on barrier function, single-cell RNA sequencing uncovered mechanistic effects of the drug on both tumor and endothelial cells. Importantly, niclosamide affected homotypic and heterotypic signaling critical to intercellular junctions, cell-matrix interactions, and cytoskeletal regulation. Proteomic analysis indicated that niclosamide-treated mice also showed reduced levels of kininogen, the precursor to the permeability mediator bradykinin. Our findings designate niclosamide as an effective drug that restricts tumor cell extravasation through modulation of signaling pathways, chemokines, and tumor-endothelial cell interactions. SIGNIFICANCE: A high-content screen identified niclosamide as an effective drug that restricts tumor cell extravasation by enhancing endothelial barrier stability through modulation of molecular signaling, chemokines, and tumor-endothelial cell interactions. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/619/F1.large.jpg.

Vav3-induced cytoskeletal dynamics contribute to heterotypic properties of endothelial barriers.

Through multiple cell-cell and cell-matrix interactions, epithelial and endothelial sheets form tight barriers. Modulators of the cytoskeleton contribute to barrier stability and act as rheostats of vascular permeability. In this study, we sought to identify cytoskeletal regulators that underlie barrier diversity across vessels. To achieve this, we correlated functional and structural barrier features to gene expression of endothelial cells (ECs) derived from different vascular beds. Within a subset of identified candidates, we found that the guanosine nucleotide exchange factor Vav3 was exclusively expressed by microvascular ECs and was closely associated with a high-resistance barrier phenotype. Ectopic expression of Vav3 in large artery and brain ECs significantly enhanced barrier resistance and cortical rearrangement of the actin cytoskeleton. Mechanistically, we found that the barrier effect of Vav3 is dependent on its Dbl homology domain and downstream activation of Rap1. Importantly, inactivation of Vav3 in vivo resulted in increased vascular leakage, highlighting its function as a key regulator of barrier stability.