Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.

Age-related declines in cardiovascular function contribute to reduced physical capacity, both of which are independent predictors of mortality. We have previously demonstrated that glycocalyx-targeted therapy with Endocalyx™ that contains high-molecular-weight hyaluronan (HMW-HA) improves cardiovascular health in old age, raising the possibility that HMW-HA also plays a role in age-related physical dysfunction. Here, we first demonstrate that tamoxifen-inducible deletion of , which produces HMW-HA, leads to glycocalyx depletion, decreases exercise capacity, and impairs skeletal muscle respiratory capacity.

Late-Life Aerobic Exercise Attenuates DNA Damage and Telomere Dysfunction in Non-Atheroprone but Not in Atheroprone Aortic Regions.

Cellular senescence is a state of persistent cell cycle arrest and is a critical contributor to arterial aging. The primary drivers of cellular senescence are the DNA damage response (DDR) and telomere dysfunction, which is induced by increasing exposure to DNA-damaging stimuli such as atheroprone shear stress. While late-life aerobic exercise is an effective intervention to mitigate arterial aging, its specific impact on the DDR and telomere dysfunction is unknown and may not show uniform benefits across aortic regions subjected to atheroprone and non-atheroprone shear stress.

Cardio-rheumatology: integrated care and the opportunities for personalized medicine.

While severe vasculopathic manifestations of systemic sclerosis (SSc) are well-recognized, characterization of subclinical progressive vasculopathy contributing to cardiac involvement remains an unmet clinical need. This review highlights the evolving understanding of SSc heart involvement (SHI), including current standard clinical cardiac evaluation methods, prevalence of various cardiac manifestations of SHI, and advances at the forefront of precision medicine. Informed by this growing body of literature, we describe the development of a novel interdisciplinary cardio-rheumatology clinic at the Vanderbilt University Medical Center.

Sex differences in endothelial glycocalyx thickness and the response to glycocalyx-targeted therapy among older adults.

Endothelial glycocalyx thickness declines with age, potentially increasing cardiovascular disease risk. However, sex differences in glycocalyx thickness and responses to glycocalyx-targeted therapies remain unclear. This post hoc analysis examined sex differences in glycocalyx thickness and the effects of Endocalyx Pro supplementation in older adults.

Non-vitamin K oral anticoagulants and aspirin do not differ for major bleeding and intracranial hemorrhage at a mean 20 mo.

GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Hematology: [Formula: see text].

Prevalence and Characteristics of Delusional Infestation in Individuals With Opiate Use Disorders Within One Health System: A Retrospective Cross-Sectional Study.

Objective: The recent development of xylazine adulteration of the illicit opiate supply has been associated with necrotic extremity wounds of unclear pathogenesis. This study sought to understand the prevalence and characteristics of delusional infestation (DI) among patients with opiate use disorders who also carried a diagnosis of cellulitis.

Methods: A retrospective cross-sectional study was performed in one health system to identify patients with opiate use disorder and cellulitis over the past three years who also described symptoms of DI.

Trends and Disparities in CAD and AMI in the United States From 2000 to 2020.

Background: Coronary artery disease (CAD) and acute myocardial infarction (AMI) still pose a significant burden to the health care system, affecting population subgroups differently.

Objectives: The purpose of the study was to describe age, sex, and racial disparities in mortality rates for CAD and AMI in the United States between 2000 and 2020.

Methods: This was an ecological study with trend analysis of mortality rates using data from the National Centers for Disease Control and Prevention surveillance databases.

In HF, MRAs reduced HF hospitalization or CV death regardless of ejection fraction.

GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text].

Ecological Psychology: A Framework for Mentoring and Career Development in Academic Medicine.

Effective mentoring can help individuals navigate the complex, dynamic environment of academic medicine as they work to develop meaningful and fulfilling careers. Despite robust research into the characteristics of effective mentoring relationships and successful mentoring programs, resources that support mentors and mentees in engaging in career development in academic medicine are limited. Ecological psychology, a theory focusing on how the dynamic interplay between individuals and their environment influences cognition and behavior, offers a promising framework for exploring how mentors and mentees can support positive career development outcomes.

Gastric Ulcer From Prolonged Oral Iron Therapy: A Case Report and Literature Review.

Iron deficiency is a leading cause of anemia worldwide and is commonly treated with oral iron supplements, which are known for their GI side effects. We present a case of a 66-year-old woman with a history of GI bleeding and multiple comorbidities who developed a gastric ulcer after prolonged oral iron therapy. Although GI side effects are frequent with iron supplements, ulceration is rare, with only a few documented cases.

Effect of glycocalyx-targeted therapy on vascular function in older adults: a randomized controlled trial.

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro, could improve both glycocalyx thickness and endothelial function in older adults; however, this has yet to be tested. We hypothesized that Endocalyx Pro supplementation would increase glycocalyx thickness and endothelial function in older adults.

Clinical pharmacology and tolerability of REC-994, a redox-cycling nitroxide compound, in randomized phase 1 dose-finding studies.

Cerebral cavernous malformation (CCM) has variable clinical symptoms, including potentially fatal hemorrhagic stroke. Treatment options are very limited, presenting a large unmet need. REC-994 (also known as tempol), identified as a potential treatment through an unbiased drug discovery platform, is hypothesized to treat CCMs through a reduction in superoxide, a reactive oxygen species.

Unveiling the Chameleon: A Case Report on Acute Intermittent Porphyria.

Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder with low penetrance, often presenting with a broad spectrum of clinical manifestations. Acute neurovisceral attacks commonly occur in young women, mimicking signs and symptoms of other medical and psychiatric conditions, thus delaying the diagnosis. We present the case of an 18-year-old female college student with recurrent hospitalizations for intractable abdominal pain, now again with pain and new subjective hematuria.

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.

Background: Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function.

Clinical Characteristics and Outcomes of Patients With Antithyroid Drug-Related Liver Injury.

Context: Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver transplantation requirement and mortality.

Objective: The primary objective of the systematic review was to assess the clinical characteristics and outcomes of patients with drug induced liver injury (DILI) due to ATDs.

Physiological determinants of mechanical efficiency during advanced ageing and disuse.

This study aimed to determine which physiological factors impact net efficiency (ηnet) in oldest-old individuals at different stages of skeletal muscle disuse. To this aim, we examined ηnet, central haemodynamics, peripheral circulation, and peripheral factors (skeletal muscle fibre type, capillarization and concentration of mitochondrial DNA [mtDNA]). Twelve young (YG; 25 ± 2 years), 12 oldest-old mobile (OM; 87 ± 3 years), and 12 oldest-old immobile (OI; 88 ± 4 years) subjects performed dynamic knee extensor (KE) and elbow flexors (EF) exercise.

Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults.

The endothelial glycocalyx is a dynamic, gel-like layer that is critical to normal vascular endothelial function. Heparin impairs the endothelial glycocalyx and reduces vascular endothelial function in a murine model; however, this has yet to be tested in healthy humans. We hypothesized that a single bolus dose of heparin would increase circulating glycocalyx components and decrease endothelial glycocalyx thickness resulting in blunted brachial artery vasodilation in healthy younger adults.

Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction.

Systemic inhibition of the mammalian target of rapamycin (mTOR) delays aging and many age-related conditions including arterial and metabolic dysfunction. However, the mechanisms and tissues involved in these beneficial effects remain largely unknown. Here, we demonstrate that activation of S6K, a downstream target of mTOR, is increased in arteries with advancing age, and that this occurs preferentially in the endothelium compared with the vascular smooth muscle.

Reduction of double-strand DNA break repair exacerbates vascular aging.

Advanced age is the greatest risk factor for cardiovascular disease (CVD), the leading cause of death. Arterial function is impaired in advanced age which contributes to the development of CVD. One underexplored hypothesis is that DNA damage within arteries leads to this dysfunction, yet evidence demonstrating the incidence and physiological consequences of DNA damage in arteries, and in particular, in the microvasculature, in advanced age is limited.

Therapeutic strategies targeting the endothelial glycocalyx.

Purpose Of Review: This review will highlight recent studies that have examined the endothelial glycocalyx in a variety of health conditions, as well as potential glycocalyx-targeted therapies.

Recent Findings: A degraded glycocalyx is present in individuals that consume high sodium diet or have kidney disease, diabetes, preeclampsia, coronavirus disease 2019 (COVID-19), or sepsis. Specifically, these conditions are accompanied by elevated glycocalyx components in the blood, such as syndecan-1, syndecans-4, heparin sulfate, and enhanced heparinase activity.

Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments.

In advanced age, increases in oxidative stress and inflammation impair endothelial function, which contributes to the development of cardiovascular disease (CVD). One plausible source of this oxidative stress and inflammation is an increase in the abundance of senescent endothelial cells. Cellular senescence is a cell cycle arrest that occurs in response to various damaging stimuli.

Endothelial specific reduction in Arf6 impairs insulin-stimulated vasodilation and skeletal muscle blood flow resulting in systemic insulin resistance.

Background: Much of what we know about insulin resistance is based on studies from metabolically active tissues such as liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance, however, the underlying mechanisms remain incompletely understood. ADP ribosylation factor 6 (Arf6) is a small GTPase that plays a critical role in endothelial cell (EC) function.

Constrictive Pericarditis from an Atraumatic Hemopericardium After Systemic Thrombolysis for a Massive Pulmonary Embolism.

Constrictive pericarditis most commonly results from fibrosis and adhesions of the parietal and visceral pericardium due to long-standing inflammation. Common etiologies include idiopathic, post-surgical, radiation injury and infectious etiologies including tuberculosis. Traumatic hemopericardium is a rare cause of constrictive pericarditis but atraumatic hemopericardium causing constrictive pericarditis has not been reported in the literature to date.