STIM1 ablation impairs exercise-induced physiological cardiac hypertrophy and dysregulates autophagy in mouse hearts.

Cardiac stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca entry (SOCE), is a known determinant of cardiomyocyte pathological growth in hypertrophic cardiomyopathy. We examined the role of STIM1 and SOCE in response to exercise-dependent physiological hypertrophy. Wild-type (WT) mice subjected to exercise training (WT-Ex) showed a significant increase in exercise capacity and heart weight compared with sedentary (WT-Sed) mice.

Implementation and Evaluation of a Prior Authorization Workflow for New-Start Inpatient Medications in Preparation for Discharge.

Medications that require prior authorization can complicate the discharge planning process. This study implemented and evaluated a process for identifying and completing prior authorizations during the inpatient setting prior to patient discharge. A patient identification tool was developed within the electronic health record to alert the patient care resource manager of inpatient orders for targeted medications that frequently require prior authorization with the potential to delay discharge.

Which hematology/oncology patients are high priority for ambulatory clinical pharmacist review? A three-round Delphi survey by the National Comprehensive Cancer Network.

Introduction: Prioritization and acuity tools have been leveraged to facilitate targeted and efficient clinical pharmacist interventions. However, there is a lack of established pharmacy-specific acuity factors in the ambulatory hematology/oncology setting. Therefore, National Comprehensive Cancer Network's Pharmacy Directors Forum conducted a survey to establish consensus on acuity factors associated with hematology/oncology patients that are high priority for ambulatory clinical pharmacist review.

Diversity in Digital Pill Systems: Differences in Perceptions and Attitudes Towards Use of a Digital Pill System for HIV Pre-Exposure Prophylaxis Among Men Who Have Sex with Men with Diverse Racial and Ethnic Identities.

Nonadherence, particularly among men who have sex with men (MSM) with substance use disorders, increases the risk of HIV acquisition. Measuring adherence to HIV pre-exposure chemoprophylaxis (PrEP), and responding to suboptimal adherence or changes in adherence behavior remains a challenging public health problem. Despite the importance of accurate adherence measurement, there is no gold standard for detecting medication ingestion events in HIV research.

MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia.

Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this drug is associated with increases in QTc interval, which predispose patients to ventricular cardiac arrhythmias. The mechanisms involved in the disposition of dofetilide, including its movement in and out of cardiomyocytes, remain unknown.

Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia.

Background: Oxidative stress in cardiac disease promotes proarrhythmic disturbances in Ca homeostasis, impairing luminal Ca regulation of the sarcoplasmic reticulum (SR) Ca release channel, the RyR2 (ryanodine receptor), and increasing channel activity. However, exact mechanisms underlying redox-mediated increase of RyR2 function in cardiac disease remain elusive. We tested whether the oxidoreductase family of proteins that dynamically regulate the oxidative environment within the SR are involved in this process.

Pyridostigmine improves cardiac function and rhythmicity through RyR2 stabilization and inhibition of STIM1-mediated calcium entry in heart failure.

Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial effects. However, mechanisms of parasympathetic-mediated improvement in cardiac function remain unclear.

Targeting OCT3 attenuates doxorubicin-induced cardiac injury.

Doxorubicin is a commonly used anticancer agent that can cause debilitating and irreversible cardiac injury. The initiating mechanisms contributing to this side effect remain unknown, and current preventative strategies offer only modest protection. Using stem-cell-derived cardiomyocytes from patients receiving doxorubicin, we probed the transcriptomic landscape of solute carriers and identified organic cation transporter 3 (OCT3) (SLC22A3) as a critical transporter regulating the cardiac accumulation of doxorubicin.

Muscarinic-dependent phosphorylation of the cardiac ryanodine receptor by protein kinase G is mediated by PI3K-AKT-nNOS signaling.

Post-translational modifications of proteins involved in calcium handling in myocytes, such as the cardiac ryanodine receptor (RyR2), critically regulate cardiac contractility. Recent studies have suggested that phosphorylation of RyR2 by protein kinase G (PKG) might contribute to the cardioprotective effects of cholinergic stimulation. However, the specific mechanisms underlying these effects remain unclear.

Tetrodotoxin-Sensitive Neuronal-Type Na Channels: A Novel and Druggable Target for Prevention of Atrial Fibrillation.

Background Atrial fibrillation (AF) is a comorbidity associated with heart failure and catecholaminergic polymorphic ventricular tachycardia. Despite the Ca-dependent nature of both of these pathologies, AF often responds to Na channel blockers. We investigated how targeting interdependent Na/Ca dysregulation might prevent focal activity and control AF.

Chronic heart failure increases negative chronotropic effects of adenosine in canine sinoatrial cells via A1R stimulation and GIRK-mediated I.

Aims: Bradycardia contributes to tachy-brady arrhythmias or sinus arrest during heart failure (HF). Sinoatrial node (SAN) adenosine A1 receptors (ADO A1Rs) are upregulated in HF, and adenosine is known to exert negative chronotropic effects on the SAN. Here, we investigated the role of A1R signaling at physiologically relevant ADO concentrations on HF SAN pacemaker cells.

Exercise does not ameliorate cardiac dysfunction in obese mice exposed to fine particulate matter.

Background: Studies have demonstrated that exposure to fine particulate matter (PM) is linked to cardiovascular disease (CVD), which is exacerbated in patients with pre-existing conditions such as obesity. In the present study, we examined cardiac function of obese mice exposed to PM and determined if mild exercise affected cardiac function.

Methods: Obese mice (ob/ob) (leptin deficient, C57BL/6J background) were exposed to either filtered air (FA) or PM at an average concentration of 32 μg/m for 6 h/day, 5 days/week for 9 months.

Enhancement of Cardiac Store Operated Calcium Entry (SOCE) within Novel Intercalated Disk Microdomains in Arrhythmic Disease.

Store-operated Ca entry (SOCE), a major Ca signaling mechanism in non-myocyte cells, has recently emerged as a component of Ca signaling in cardiac myocytes. Though it has been reported to play a role in cardiac arrhythmias and to be upregulated in cardiac disease, little is known about the fundamental properties of cardiac SOCE, its structural underpinnings or effector targets. An even greater question is how SOCE interacts with canonical excitation-contraction coupling (ECC).

Development and validation of a UPLC-MS/MS analytical method for dofetilide in mouse plasma and urine, and its application to pharmacokinetic study.

A novel method using UPLC with tandem mass-spectrometric detection (UPLC-MS/MS) with positive electrospray ionization was developed for the detection of the antiarrhythmic drug, dofetilide, in mouse plasma and urine. Protein precipitation was performed on 10 μL of plasma and 2 μL of urine samples using dofetilide-D4 as an internal standard, and separation of the analyte was accomplished on a C18 analytical column with the flow of 0.40 mL/min.

The role of luminal Ca regulation in Ca signaling refractoriness and cardiac arrhythmogenesis.

Györke et al. discuss the role of sarcoplasmic reticulum Ca in cardiac refractoriness and pathological implications.

The role of spatial organization of Ca release sites in the generation of arrhythmogenic diastolic Ca release in myocytes from failing hearts.

In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca imaging were applied to study spatially defined Ca handling in ventricular myocytes isolated from normal (control) and failing canine hearts.

Evaluation of a pharmacist-managed electrolyte protocol in outpatients on antiarrhythmic medications.

Objective: To evaluate the effectiveness of a pharmacist-managed treatment protocol in achieving and maintaining serum potassium level ([K]) in the desired range.

Setting: Antiarrhythmic Medications Clinic, The Ohio State University Wexner Medical Center, Columbus, Ohio, from 2009 to 2013.

Practice Description: Patients are referred for antiarrhythmic monitoring at this pharmacist-run, electrophysiologist-supervised clinic.

In Utero Particulate Matter Exposure Produces Heart Failure, Electrical Remodeling, and Epigenetic Changes at Adulthood.

Background: Particulate matter (PM; PM [PM with diameters of <2.5 μm]) exposure during development is strongly associated with adverse cardiovascular outcomes at adulthood. In the present study, we tested the hypothesis that in utero PM exposure alone could alter cardiac structure and function at adulthood.

Muscarinic Stimulation Facilitates Sarcoplasmic Reticulum Ca Release by Modulating Ryanodine Receptor 2 Phosphorylation Through Protein Kinase G and Ca/Calmodulin-Dependent Protein Kinase II.

Although the effects and the underlying mechanism of sympathetic stimulation on cardiac Ca handling are relatively well established both in health and disease, the modes of action and mechanisms of parasympathetic modulation are poorly defined. Here, we demonstrate that parasympathetic stimulation initiates a novel mode of excitation-contraction coupling that enhances the efficiency of cardiac sarcoplasmic reticulum Ca store utilization. This efficient mode of excitation-contraction coupling involves reciprocal changes in the phosphorylation of ryanodine receptor 2 at Ser-2808 and Ser-2814.

Chronic Omega-3 Polyunsaturated Fatty Acid Treatment Variably Affects Cellular Repolarization in a Healed Post-MI Arrhythmia Model.

Introduction: Over the last 40 years omega-3 polyunsaturated fatty acids (PUFAs) have been shown to be anti-arrhythmic or pro-arrhythmic depending on the method and duration of administration and model studied. We previously reported that omega-3 PUFAs do not confer anti-arrhythmic properties and are pro-arrhythmic in canine model of sudden cardiac death (SCD). Here, we evaluated the effects of chronic omega-3 PUFA treatment in post-MI animals susceptible (VF+) or resistant (VF-) to ventricular tachyarrhythmias.

"Know Hepatitis B:" A Multilingual Communications Campaign Promoting Testing for Hepatitis B Among Asian Americans and Pacific Islanders.

The "Know Hepatitis B" campaign was the first national, multilingual communications campaign to promote testing for hepatitis B virus (HBV) among Asian Americans and Pacific Islanders (AAPIs). This population comprises fewer than 5% of the total U.S.

"Know More Hepatitis:" CDC's National Education Campaign to Increase Hepatitis C Testing Among People Born Between 1945 and 1965.

In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C.

Dysfunction of the β2-spectrin-based pathway in human heart failure.

β2-Spectrin is critical for integrating membrane and cytoskeletal domains in excitable and nonexcitable cells. The role of β2-spectrin for vertebrate function is illustrated by dysfunction of β2-spectrin-based pathways in disease. Recently, defects in β2-spectrin association with protein partner ankyrin-B were identified in congenital forms of human arrhythmia.

Protein phosphatase 2A regulatory subunit B56α limits phosphatase activity in the heart.

Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme composed of a catalytic, scaffolding, and regulatory subunit. In the heart, PP2A activity is requisite for cardiac excitation-contraction coupling and central in adrenergic signaling. We found that mice deficient in the PP2A regulatory subunit B56α (1 of 13 regulatory subunits) had altered PP2A signaling in the heart that was associated with changes in cardiac physiology, suggesting that the B56α regulatory subunit had an autoinhibitory role that suppressed excess PP2A activity.