Myocardial fibrosis in stroke survivors

Stroke survivors are most likely to die of cardiac death, yet few undergo comprehensive cardiac assessment to look for reversible causes. Myocardial fibrosis (MF) is not only the hallmark of cardiomyopathy, but also a substrate for sudden cardiac death, ventricular tachyarrhythmia and heart failure. Procollagen carboxyl-terminal telopeptide (PICP) was found to be a marker of MF. The relationship between PICP and cardiac abnormalities in stroke survivors is unknown. We recently showed that MF in stroke survivors can be treated by spironolactone and amiloride in a randomised placebo-controlled cross-over study with reduction in PICP levels and QTc [1]

The effect of infrared beak treatment on the welfare of turkeys reared to 12 weeks of age

This study aimed to determine the effects of infrared beak treatment on the behavior and welfare of male and female turkeys reared to 12 wk of age. To do this, poults (236 males and 324 females) were assigned to one of 2 beak treatments: infrared beak treated on day of hatch (IR) or sham untreated control (C). Data collected included heterophil/lymphocyte (H/L) ratio, pecking force, feather cover, behavioral expression, and beak histology. Data were analyzed as a 2 × 2 factorial of beak treatment and gender, in a completely randomized design and analyzed using PROC MIXED (SAS 9.4). H/L ratio (indicative of a stress response) did not differ between treated and control poults during early life, except at 20 d of age when H/L ratio was higher for C poults than IR poults. Pecking force, measured as a method of monitoring pain, was different only at 1 wk of age, when IR poults pecked with more force than C poults. Feather cover was better in IR poults at 12 wk of age. Differences in behavior between treatments were minor over the 12-wk period. Overall, infrared beak treatment of commercial turkeys had minimal negative impacts on behavior and welfare. The results suggest that stress may be reduced in flocks that are beak treated and that the procedure itself does not cause a pain response

The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic

Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure:The REFORM Trial

OBJECTIVE To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI. RESEARCH DESIGN AND METHODS We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters. RESULTS In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight. CONCLUSIONS We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown

Association between mitochondrial function measured by 31P Magnetic Resonance Spectroscopy and physical performance in older people with functional impairment

Abstract Background Mitochondrial dysfunction is a potential therapeutic target to improve skeletal muscle function, but the contribution of mitochondrial dysfunction to impaired skeletal muscle performance in older people remains unclear. The aim of this analysis was to test the association between measures of skeletal muscle mitochondrial function and physical performance in older people. Methods We analysed data from the Allopurinol in Functional Impairment trial. Participants aged 65 and over, who were unable to walk 400 m in 6 min, underwent 31P magnetic resonance spectroscopy of the calf after exercise at baseline and at 20 weeks follow up. The phosphocreatine recovery half‐life time (t1/2) was derived as a measure of mitochondrial function. Participants undertook the 6‐min walk test and the Short Physical Performance Battery. Muscle mass measured using the Akern 101 bio‐impedance analysis system. Bivariate correlations and multivariable regression analyses were conducted to determine associations between t1/2 and baseline factors. Results One hundred and seventeen participants underwent baseline 31P magnetic resonance spectroscopy, mean age 80.4 years (SD 6.0); 56 (48%) were female. Mean 6‐min walk was 291 m (SD 80), mean SPPB score was 8.4 (SD 1.9); t1/2 correlated significantly with Short Physical Performance Battery score (r = 0.22, P = 0.02) but not with 6‐min walk distance (r = 0.10, P = 0.29). In multivariable linear regression, muscle mass and total body weight, but not t1/2, were independently associated with Short Physical Performance Battery score and with 6‐min walk distance. Change in t1/2 was not significantly associated with change in Short Physical Performance Battery score (r = 0.03, P = 0.79) or with change in 6‐min walk distance (r = −0.11, P = 0.28). Conclusions Muscle mass, but not phosphocreatine recovery time, was consistently associated with Short Physical Performance Battery score and 6‐min walk distance in older people with functional impairment

Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).

AIM: Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months. CONCLUSIONS: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size