DNA demethylation fine-tunes IL-2 production during thymic regulatory T cell differentiation.

Regulatory T (T reg) cells developing in the thymus are essential to maintain tolerance and prevent fatal autoimmunity in mice and humans. Expression of the T reg lineage-defining transcription factor FoxP3 is critically dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that ten-eleven translocation (Tet) enzymes, which are DNA demethylases, are required early during double-positive (DP) thymic T cell differentiation and prior to the upregulation of FoxP3 in CD4 single-positive (SP) thymocytes, to promote Treg differentiation.

Severe Anti-HMG-CoAR Necrotizing Autoimmune Myopathy Secondary to Statin Use.

Immune-mediated necrotizing myopathy is an uncommon but debilitating disease that can be triggered by drugs, toxins, or cancer. It is similar to polymyositis in presentation but is differentiated by findings on muscle biopsy. We present a case of a 79-year-old male on statin therapy who presented with proximal muscle weakness and elevated creatinine kinase (CK) levels.

Antiphospholipid antibodies and vitamin D deficiency in COVID-19 infection with and without venous or arterial thrombosis: A pilot case-control study.

Background: Coronavirus disease-2019 (COVID-19) is associated with thromboembolism. Antiphospholipid antibody (APLa) formation is one of the mechanisms. Vitamin D deficiency has been associated with thrombosis in antiphospholipid antibody syndrome.

CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element.

The epigenetic patterns that are established during early thymic development might determine mature T cell physiology and function, but the molecular basis and topography of the genetic elements involved are not fully known. Here we show, using the Cd4 locus as a paradigm for early developmental programming, that DNA demethylation during thymic development licenses a novel stimulus-responsive element that is critical for the maintenance of Cd4 gene expression in effector T cells. We document the importance of maintaining high CD4 expression during parasitic infection and show that by driving transcription, this stimulus-responsive element allows for the maintenance of histone H3K4me3 levels during T cell replication, which is critical for preventing de novo DNA methylation at the Cd4 promoter.

Occurrence of Post-Transplant Lymphoproliferative Disease in a Renal Transplant Patient.

Post-transplant lymphoproliferative diseases (PTLD) are a group of lymphoid disorders that occur in the setting of solid organ or hematopoietic transplantation. Risk factors for the development of PTLD include type of organ transplanted, degree/duration of T-cell immunosuppression, and Epstein-Barr virus (EBV) status. After initial infection, EBV lies dormant in memory B-cells and persists at low levels throughout the lifetime.

Increased Mortality in Antecedent Combined Renin-Angiotensin System Inhibitors and Antiplatelets Compared With Antiplatelets Alone in Hospitalized Patients With COVID-19.

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Lithium-Induced Brugada Pattern: A Case Report and Review of Literature.

Lithium-induced type 1 Brugada pattern in asymptomatic patients is an uncommon occurrence that is challenging to manage and to estimate the risk of sudden cardiac death (SCD). We describe a case of a 74-year-old woman who presented with type 1 Brugada pattern while on lithium therapy. Her lithium level was within the therapeutic range at the time of presentation.

A systematic review and meta-analysis comparing second-generation cryoballoon and contact force radiofrequency ablation for initial ablation of paroxysmal and persistent atrial fibrillation.

Introduction: Cryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the preferred modalities for catheter ablation of atrial fibrillation (AF). Technological advances have improved procedural outcomes, warranting an updated comparison. We sought to evaluate the efficacy and safety of CBA-2nd generation (CBA-2G) in comparison to RFA-contact force (RFA-CF) in patients with AF.

The Indian gut microbiota-Is it unique?

Colonization of the gut by microbes depends on a number of factors including age, diet, genetic makeup, gender, geographic location, and health status of an individual. India is a megadiverse country and includes 4 biodiversity hot spots. These features, along with the transitioning Indian sociodemographic profile, make the gut microbiota of Indian subjects an interesting area to study.

Loss of iRhom2 accelerates fat gain and insulin resistance in diet-induced obesity despite reduced adipose tissue inflammation.

Background: Low-grade inflammation and metabolic dysregulation are common comorbidities of obesity, both of which are associated with alterations in iRhom2-regulated pro-inflammatory cytokine and epidermal growth factor receptor (EGFR) ligand signaling.

Objective: Our objective was to determine the role of iRhom2 in the regulation of low-grade inflammation and metabolic dysregulation in a murine model of diet-induced obesity.

Methods: Wild type (WT) and iRhom2-deficient mice were fed normal chow (NC) or a high-fat diet (HFD) starting at 5 weeks of age for up to 33 weeks.

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Background: Glucagon-like peptide-1 receptor agonists (GLP1RAs) are relatively newer anti-hyperglycemic agents, which have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus.

Design: We performed a meta-analysis of randomized controlled trials to evaluate the cardiovascular outcomes of GLP1RAs compared to placebo in type 2 diabetes mellitus patients. We performed an additional subgroup analysis to evaluate the role of GLP1RAs in patients with chronic kidney disease.

Meta-Analysis Comparing Double Versus Triple Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Disease.

Atrial fibrillation (AF) and concomitant coronary artery disease (CAD) create a therapeutic dilemma as the risk of bleeding with triple antithrombotic therapy (TATT) must be balanced against the risk of ischemic events with double antithrombotic therapy (DATT). The aim of this meta-analysis is to compare the efficacy and safety of DATT versus TATT in AF and CAD. MEDLINE, Cochrane, and ClinicalTrials.

Prosthetic Mitral Valve Obstruction with Left Atrial Appendage Thrombus: A Therapeutic Dilemma.

Valvular obstruction is a rare but life-threatening complication of mechanical prosthetic valves that raises significant challenges in management. We describe a unique case of mechanical mitral valve obstruction with co-existing left atrial appendage (LAA) thrombus. A 48-year-old man with a past medical history of atrial fibrillation and mechanical mitral valve replacement 18 months prior, presented with symptoms of new onset heart failure for 10 days.