Insights from the sequence similarity of Zika virus proteins with the Human nerve proteins.

Massive peptide sharing between the Zika virus polyprotein and host tissue proteins could elicit significant host-pathogen interactions and cross-reactions leading to autoimmune diseases. This study found similarities in the Zika V proteins and human nerve tissue proteins. 63 human nerve proteins were screened for similarities with the Zika V of which Neuromodulin, Nestin, Galanin, Bombesin, Calcium-binding protein were found to have similarities to the Zika V poly protein C at different sequence regions.

Do implantable cardioverter defibrillators improve survival in patients with chronic kidney disease at high risk of sudden cardiac death? A meta-analysis of observational studies.

Aims: Prospective randomized clinical trials show that implantable cardioverter defibrillators (ICDs) can reduce the risk of total mortality in select populations. However, data regarding patients with chronic kidney disease (CKD) are inconclusive. The aim of this study was to evaluate if ICDs affect total mortality in CKD patients at high risk of sudden cardiac death.

Oxidized Ca(2+)/calmodulin-dependent protein kinase II triggers atrial fibrillation.

Background: Atrial fibrillation (AF) is a growing public health problem without adequate therapies. Angiotensin II and reactive oxygen species are validated risk factors for AF in patients, but the molecular pathways connecting reactive oxygen species and AF are unknown. The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a reactive oxygen species-activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ could contribute to AF.

Phosphoproteomics study based on in vivo inhibition reveals sites of calmodulin-dependent protein kinase II regulation in the heart.

Background: The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is a crucial mediator of cardiac physiology and pathology. Increased expression and activation of CaMKII has been linked to elevated risk for arrhythmic events and is a hallmark of human heart failure. A useful approach to determining CaMKII's role therein is large-scale analysis of phosphorylation events by mass spectrometry.

Diabetes increases mortality after myocardial infarction by oxidizing CaMKII.

Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca(2+)/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction.

Genetic inhibition of Na+-Ca2+ exchanger current disables fight or flight sinoatrial node activity without affecting resting heart rate.

Rationale: The sodium-calcium exchanger 1 (NCX1) is predominantly expressed in the heart and is implicated in controlling automaticity in isolated sinoatrial node (SAN) pacemaker cells, but the potential role of NCX1 in determining heart rate in vivo is unknown.

Objective: To determine the role of Ncx1 in heart rate.

Methods And Results: We used global myocardial and SAN-targeted conditional Ncx1 knockout (Ncx1(-/-)) mice to measure the effect of the NCX current on pacemaking activity in vivo, ex vivo, and in isolated SAN cells.

Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias.

Understanding relationships between heart failure and arrhythmias, important causes of suffering and sudden death, remains an unmet goal for biomedical researchers and physicians. Evidence assembled over the past decade supports a view that activation of the multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca(2+) or oxidation, upstream signals with the capacity to transition CaMKII into a Ca(2+) and calmodulin-independent constitutively active enzyme.

Are treatments for vasovagal syncope effective? A meta-analysis.

Background: Therapies used to treat vaso-vagal syncope (VVS) recurrence have not been proven effective in single studies.

Methods: Comprehensive search of PubMed, EMBASE and Cochrane Central databases of published trials was done. Randomized or non-randomized studies, comparing the intervention of interest to control group(s), with the endpoint of spontaneous recurrence or syncope on head-up tilt test, were included.

MyD88 mediated inflammatory signaling leads to CaMKII oxidation, cardiac hypertrophy and death after myocardial infarction.

The toll-like receptors (TLR) and myocardial infarction (MI) promote NF-κB-dependent inflammatory transcription and oxidative injury in myocardium. The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by oxidation and contributes to NF-κB-dependent transcription, myocardial hypertrophy and post-MI death. The myeloid differentiation protein 88 (MyD88) is an adapter protein critical for many TLR functions, but downstream targets for TLR/MyD88 signaling in MI are not well understood.

Oxidation of CaMKII determines the cardiotoxic effects of aldosterone.

Excessive activation of the β-adrenergic, angiotensin II (Ang II) and aldosterone signaling pathways promotes mortality after myocardial infarction, and antagonists targeting these pathways are core therapies for treating this condition. Catecholamines and Ang II activate the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), the inhibition of which prevents isoproterenol-mediated and Ang II-mediated cardiomyopathy. Here we show that aldosterone exerts direct toxic actions on myocardium by oxidative activation of CaMKII, causing cardiac rupture and increased mortality in mice after myocardial infarction.

Oxidized CaMKII causes cardiac sinus node dysfunction in mice.

Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress.

RGS6, a modulator of parasympathetic activation in heart.

Rationale: Parasympathetic regulation of heart rate is mediated by acetylcholine binding to G protein-coupled muscarinic M2 receptors, which activate heterotrimeric G(i/o) proteins to promote G protein-coupled inwardly rectifying K(+) (GIRK) channel activation. Regulator of G protein signaling (RGS) proteins, which function to inactivate G proteins, are indispensable for normal parasympathetic control of the heart. However, it is unclear which of the more than 20 known RGS proteins function to negatively regulate and thereby ensure normal parasympathetic control of the heart.

Comparison of low molecular weight heparin with unfractionated heparin during percutaneous coronary interventions: a meta-analysis.

To conduct a meta-analysis of the current evidence to evaluate the safety and efficacy of low molecular weight heparin (LMWH) as compared to unfractionated heparin (UFH). Several studies have demonstrated the therapeutic advantage of LMWH over UFH in the medical management of acute coronary syndromes. However, evidence comparing the 2 in percutaneous coronary interventions (PCI) is inconclusive.

Pharmacotherapy plus endoscopic intervention is more effective than pharmacotherapy or endoscopy alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized, controlled trials.

Background: Previous clinical trials on the treatment of esophageal variceal bleeding yielded mixed results regarding the efficacy of endoscopic procedures compared with pharmacotherapy only.

Objective: To compare the efficacy of endoscopic procedures with that of pharmacotherapy in the prevention of mortality and rebleeding.

Design And Setting: A systematic literature review was performed to identify randomized, controlled trials of the efficacy of pharmacotherapy and endoscopic therapy.

Normal coronary arteries in patients with systolic heart failure who have higher body mass index.

Background: Previous research has shown an association between higher body mass index (BMI) and lower mortality in patients with heart failure (HF).

Methods: We compared the prevalence of angiographic coronary artery disease (CAD) and risk factors in obese versus non-obese patients with HF. Eighty-four consecutive patients with systolic HF who underwent coronary angiography in a single institution were categorized by BMI into non-obese (BMI < 30, n = 42) and obese (BMI >or= 30, n = 42) subjects.

Intravenously injected mesenchymal stem cells home to viable myocardium after coronary occlusion and preserve systolic function without altering infarct size.

Background: The purpose of this study was to determine whether murine mesenchymal stem cells (MSC) are able to home to the viable myocardium when injected intravenously and attenuate cardiac dysfunction and ventricular remodeling associated with myocardial infarction.

Methods And Results: Murine bone marrow cells were negatively selected for lineage markers and adherent MSC differentiated into adipocytes and osteocytes following treatment in culture. Two weeks after coronary occlusion that resulted in a permanent transmural infarct we observed a significant drop in LV systolic pressure, dP/dt(max), dP/dt(min), ESPVR and E(max) and a significant increase in end-diastolic volume in vivo.

Obesity is associated with higher mortality in patients with cardiogenic shock.

Cardiogenic shock is the leading cause of death in patients with acute myocardial infarction. Studies that have focused on identifying mortality predictors in patients with cardiogenic shock have not evaluated outcomes in obese patients. A study of sixty-one patients with cardiogenic shock demonstrated that obese patients with cardiogenic shock have a higher mortality risk compared to non-obese patients.