Long-term Prognostic Value of Cardiac MRI Left Atrial Strain in ST-Segment Elevation Myocardial Infarction

Background: Left atrial (LA) dysfunction is associated with morbidity and mortality. To the knowledge of the authors, the relationship of LA strain to long-term prognosis in participants with ST-segment elevation myocardial infarction (STEMI) is unknown. / Purpose: To evaluate LA strain as a long-term outcome predictor in STEMI in a prospective, multicenter cardiac MRI cohort. / Materials and Methods: Participants with STEMI who underwent primary percutaneous coronary intervention and cardiac MRI from 10 sites (EARLY-MYO-CMR registry, clinical trial number NCT03768453) were included. The parent study took place between August 2013 and December 2018. LA longitudinal strain and strain rate parameters were derived from cine cardiac MRI by using an in-house semiautomated method. Major adverse cardiac events (MACEs) were defined as cardiovascular death, myocardial reinfarction, hospitalization for heart failure, and stroke. The association between LA performance and MACE was evaluated by using time-dependent receiver operating characteristic analysis, Kaplan-Meier analysis, and multivariable Cox regression analysis. / Results: A total of 321 participants (median age, 59 years; age range, 27–75 years; 90% men) were included in this study. During median follow-up of 3.7 years, MACE occurred in 76 participants (23.7%). Participants with impaired reservoir (≤22%) and conduit strain (≤10%) had a higher risk of MACE than those with reservoir strain greater than 22% and conduit strain greater than 10% (P < .001). Reservoir strain (hazard ratio, 0.84; 95% confidence interval: 0.77, 0.91; P < .001) and conduit strain (hazard ratio, 0.81; 95% confidence interval: 0.73, 0.89; P < .001) were independent predictors for MACE after adjustment for known risk factors. Finally, LA reservoir and conduit strains provided incremental prognostic value over traditional outcome predictors (Uno C statistic comparing models, 0.75 vs 0.68; P = .04). / Conclusion: Assessment of left atrial strain, as a measure of left atrial function, provided incremental prognostic information to established predictors in ST-segment elevation myocardial infarction

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Background: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic–pituitary–adrenal axis and heightened chronic systemic inflammation appear to be major contributors. Methods: We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci. Results: The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, β = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, β = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant. Conclusions: We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results

Practicing a Musical Instrument in Childhood is Associated with Enhanced Verbal Ability and Nonverbal Reasoning

Background: In this study we investigated the association between instrumental music training in childhood and outcomes closely related to music training as well as those more distantly related. Methodology/Principal Findings: Children who received at least three years (M = 4.6 years) of instrumental music training outperformed their control counterparts on two outcomes closely related to music (auditory discrimination abilities and fine motor skills) and on two outcomes distantly related to music (vocabulary and nonverbal reasoning skills). Duration of training also predicted these outcomes. Contrary to previous research, instrumental music training was not associated with heightened spatial skills, phonemic awareness, or mathematical abilities. Conclusions/Significance: While these results are correlational only, the strong predictive effect of training duration suggests that instrumental music training may enhance auditory discrimination, fine motor skills, vocabulary, and nonverba

Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA

10.1371/journal.pone.0066712PLoS ONE86

Mortality in Peripheral Arterial Disease: A Comparison of Patients Managed by Vascular Specialists and General Practitioners

BACKGROUND: Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE: To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN: Prospective study. SETTING: Primary care practice and academic vascular laboratory. PARTICIPANTS: GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrolment period of the PACE study. MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01–0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01–0.65; p = .020), after adjustment for patients’ characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01–0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01–0.71, p = .033). CONCLUSIONS: Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists

Perturbation and numerical study of double-diffusive dissipative reactive convective flow in an open vertical duct containing a non-darcy porous medium with robin boundary conditions

A mathematical model for thermosolutal convection flow in an open two-dimensional vertical channel containing a porous medium saturated with reactive Newtonian fluid is developed and studied. Robin boundary conditions are prescribed, and a first-order homogenous chemical reaction is considered. The Darcy–Forchheimer model is used to simulate both the first- and second-order porous mediums’ drag effects. For the general non-Darcy-case, a numerical solution is presented using the Runge–Kutta quadrature and a shooting method. The influences of thermal (0≤λ1≤15) and solute Grashof numbers (0≤λ2≤20) , Biot numbers (1≤Bi1≤10,Bi2=10) , Brinkman number (0≤Br≤0.5) , first-order chemical reaction parameter (2≤α≤8) , porous medium parameter (2≤σ≤8) and Forchheimer (inertial drag) parameter (0≤I≤12) on the evolutions of velocity, temperature and concentration (species) distributions are visualized graphically. Nusselt number and skin friction at the walls are also computed for specific values of selected parameters. The study is relevant to the analysis of geothermal energy systems with chemical reaction

Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.</p> <p>Methods</p> <p>In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes.</p> <p>Results</p> <p>One hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (<it>P </it>< 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; <it>P </it>< 0.001) and vomiting (12.4% vs. 2.0%; <it>P </it>= 0.005).</p> <p>Conclusions</p> <p>Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00136201</p