Alterations in the inflammatory homeostasis of aging-related cardiac dysfunction and Alzheimer's diseases.

Alzheimer's disease (AD) is well known among the elderly and has a profound impact on both patients and their families. Increasing research indicates that AD is a systemic disease, with a strong connection to cardiovascular disease. They share common genetic factors, such as mutations in the presenilin (PS1 and PS2) and the apolipoprotein E (APOE) genes.

Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Metabolic imbalances and pathological stress often contribute to increased mortality. Sestrin2 (Sesn2) is a stress-inducible protein crucial in maintaining cardiac energy and metabolic homeostasis under pathological conditions.

Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.

Background: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group.

Methods: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT).

Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.

Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1).

Recommendations for clinical decision-making when offering exoskeletons for community use in individuals with spinal cord injury.

Approved in 2014 by the Food and Drug Administration (FDA) for use with a trained companion, personal powered exoskeletons (PPE) for individuals with spinal cord injury (SCI) provide an opportunity for the appropriate candidate to ambulate in their home and community. As an adjunct to wheeled mobility, PPE use allows those individuals who desire to ambulate the opportunity to experience the potential physiological and psychosocial benefits of assisted walking outside of a rehabilitation setting. There exists, however, a knowledge gap for clinicians regarding appropriate candidate selection for use, as well as who might benefit from ambulating with a PPE.

Myeloid Cells in Myocardial Ischemic Injury: The Role of the Macrophage Migration Inhibitory Factor.

Ischemic heart disease, manifesting as myocardial infarction (MI), remains the leading cause of death in the western world. Both ischemia and reperfusion (I/R) cause myocardial injury and result in cardiac inflammatory responses. This sterile inflammation in the myocardium consists of multiple phases, involving cell death, tissue remodeling, healing, and scar formation, modulated by various cytokines, including the macrophage migration inhibitory factor (MIF).

Platelets at the intersection of inflammation and coagulation in the APC-mediated response to myocardial ischemia/reperfusion injury.

Thromboinflammation is a complex pathology associated with inflammation and coagulation. In cases of cardiovascular disease, in particular ischemia-reperfusion injury, thromboinflammation is a common complication. Increased understanding of thromboinflammation depends on an improved concept of the mechanisms of cells and proteins at the axis of coagulation and inflammation.

Assessment of Physician Needs and Access to Inflammatory Bowel Disease Specialty Care Resources in a National Integrated Health System.

Background: The barriers to providing high-quality inflammatory bowel disease (IBD) care go beyond educational needs alone to include access to IBD-related resources such as medications, laboratory testing, and multidisciplinary teams. We assessed the needs and resource constraints of physicians caring for Veterans with IBD to inform efforts to improve access to high-quality care.

Methods: We conducted a national observational survey study in July 2021 of gastroenterologists (GIs) and primary care providers (PCPs) caring for Veterans with IBD within the Veterans Health Administration with the intent of including physicians from all 18 Veterans Integrated Service Networks (VISN).

Cardiac diastolic dysfunction by cigarette smoking is associated with mitochondrial integrity in the heart.

Cigarette smoking behaviors are harmful and cause one out of ten deaths due to cardiovascular disease. As population sizes grow and number of cigarette smokers increases, it is vital that we understand the mechanisms leading to heart failure in cigarette smokers. We have reported that metabolic regulation of a histone deacetylase, SIRT1, modulates cardiovascular and mitochondrial function under stress.

Supporting direct acting antiviral medication adherence and treatment completion in a sample of predominantly rural veterans with hepatitis C and substance use disorders.

Background: Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans.

Methods: We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment.

Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.

Context: The search for somatic mutations in adrenals resected from patients with primary aldosteronism (PA) is performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas.

Objective: To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next-generation sequencing (NGS).

Methods: We investigated 127 consecutive adrenal aldosterone-producing adenomas from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, by Sanger sequencing and NGS.

Familial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series.

Eye Plaque Brachytherapy for Choroidal Malignant Melanoma: A Case Report on the Use of Innovative Technology to Expand Access, Improve Practice, and Enhance Outcomes.

Our institute established an eye plaque interstitial brachytherapy (EPIBT) program in 2007 using the Collaborative Ocular Melanoma Study (COMS) eye plaque. In this case report, we demonstrated an eye plaque treatment planned and executed using Eye Physics Plaque (Los Alamitos, CA) for a 72-year-old male patient with an extra-large tumor with a maximum width of 18.6 mm and height of 13.

Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer's disease by activated protein C.

Single-Cell RNA sequencing reveals changes in cell population in Alzheimer's disease (AD) model 5xFAD (5x Familial AD mutation) versus wild type (WT) mice. The returned sequencing data was processed through the 10x Genomics platform to perform alignment and form corresponding matrix to perform bioinformatic analysis. Alterations in glial cells occurred in 5xFAD versus WT, especially increases in microglia proliferation were profound in 5xFAD.

Chronic activation of adrenal Gq signaling induces Cyp11b2 expression in the zona fasciculata and hyperaldosteronism.

Hyperaldosteronism is often associated with inappropriate aldosterone production and aldosterone synthase (Cyp11b2) expression. Normally, Cyp11b2 expression is limited to the adrenal zona glomerulosa (ZG) and regulated by angiotensin II which signals through Gq protein-coupled receptors. As cells migrate inwards, they differentiate into 11β-hydroxylase-expressing zona fasciculata (ZF) cells lacking Cyp11b2.

mTOR Regulates Mineralocorticoid Receptor Transcriptional Activity by ULK1-Dependent and -Independent Mechanisms.

The mineralocorticoid receptor (MR) is a transcription factor for genes mediating diverse, cell-specific functions, including trophic effects as well as promoting fluid/electrolyte homeostasis. It was reported that in intercalated cells, phosphorylation of the MR at serine 843 (S843) by Unc-51-like kinase (ULK1) inhibits MR activation and that phosphorylation of ULK1 by mechanistic target of rapamycin (mTOR) inactivates ULK1, and thereby prevents MR inactivation. We extended these findings with studies in M1 mouse cortical collecting duct cells stably expressing the rat MR and a reporter gene.

A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation.

Macrophage migration inhibitory factor (MIF) is an innate cytokine that regulates both inflammatory and homeostatic responses. MIF is expressed by cardiomyocytes, where it exerts a protective action against ischemia-reperfusion (I/R) injury by activating AMP-activated protein kinase (AMPK). This effect is attenuated in the senescent heart due to an intrinsic, age-related reduction in MIF expression.

Screening for Elder Abuse in the Veterans Health Administration: Varied Approaches Across a National Health System.

Background: Elder abuse (EA) is common and has devastating health consequences yet is rarely detected by healthcare professionals. While EA screening tools exist, little is known about if and how these tools are implemented in real-world clinical settings. The Veterans Health Administration (VHA) has experience screening for, and resources to respond to, other forms of interpersonal violence and may provide valuable insights into approaches for EA screening.

A smoking cessation intervention for rural veterans tailored to individual risk factors: A multicenter randomized clinical trial.

Introduction: Rates of cigarette use remain elevated among those living in rural areas. Depressive symptoms, risky alcohol use, and weight concerns frequently accompany cigarette smoking and may adversely affect quitting. Whether treatment for tobacco use that simultaneously addresses these issues affects cessation outcomes is uncertain.

Alterations of SIRT1/SIRT3 subcellular distribution in aging undermine cardiometabolic homeostasis during ischemia and reperfusion.

Age-related sensors Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) play an essential role in the protective response upon myocardial ischemia and/or reperfusion (I/R). However, the subcellular localization and co-regulatory network between cardiac SIRT1 and SIRT3 remain unknown, especially their effects on age-related metabolic regulation during acute ischemia and I/R. Here, we found that defects of cardiac SIRT1 or SIRT3 with aging result in an exacerbated cardiac physiological structural and functional deterioration after acute ischemic stress and failed recovery through reperfusion operation.

Olanzapine-induced mania.

Olanzapine is a relatively new antipsychotic agent which appears to be effective in the treatment of both the positive and negative symptoms of schizophrenia. Reported here is the case of a patient who developed symptoms of mania secondary to treatment with olanzapine. Physicians prescribing olanzapine should be aware of this potential complication.

18-Oxocortisol: A journey.

The search for mineralocorticoids to explain some cases of low renin hypertension with suppressed aldosterone levels led to the isolation of the abundant steroid 18-hydroxycortisol in human urine. 18-Hydroxycortisol proved to be inactive, but because of its similarity to precursors for the synthesis of aldosterone, bullfrog adrenals were incubated with cortisol, resulting in the discovery of 18-oxocortisol which is structurally similar to aldosterone, but with a 17α-hydroxy group like cortisol. 18-Oxocortisol is a weak mineralocorticoid.

An Abbreviated History of Aldosterone Metabolism, Current and Future Challenges.

The initial isolation of adrenal steroids from large quantities of animal adrenals resulted in an amorphous fraction resistant to crystallization and identification and had potent effects on electrolyte transport. Aldosterone was eventually isolated and identified in the fraction and was soon shown to cause hypertension when in excess. The autonomous and excessive production of aldosterone, primary aldosteronism, is the most common cause of secondary hypertension.