Prevalence of diabetic and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities

Background: In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods: CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia and Africa in 2009-2010, and followed-up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia, or prior revascularisation procedure. Results: Among 32,694patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to approximately 60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome(cardiovascular death, myocardial infarction or stroke)with an adjusted hazard ratio of1.28(95% CI 1.18-1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion: In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes

Electrocardiographic Findings in Patients with Acute Coronary Syndrome Presenting with Out-of-Hospital Cardiac Arrest

We sought to characterize presenting electrocardiographic findings in patients with acute coronary syndromes (ACS) and out-of-hospital cardiac arrest (OHCA). In the Global Registry of Acute Coronary Events (GRACE) and Canadian ACS Registry I, we examined presenting and 24-48 hour follow-up ECGs of ACS patients who survived to hospital admission, stratified by presentation with OHCA. We assessed the prevalence of ST-segment deviation and bundle branch blocks and their association with in-hospital and 6-month mortality amongst those with OHCA. 215 (1.8%) of 12,040 ACS patients survived to hospital admission following OHCA. Those with OHCA had higher presenting rates of ST-segment elevation, ST-segment depression, T wave inversion, precordial Q waves, left bundle branch block (LBBB), and right bundle branch block (RBBB) than those without. Among patients with OHCA, those with ST-segment elevation had significantly lower in-hospital mortality (20.9% vs. 33.0%, p=0.044) and a trend toward lower 6-month mortality (27% vs. 39%, p=0.060) compared to those without ST-segment elevation. Conversely, among OCHA patients, LBBB was associated with significantly higher in-hospital and 6-month mortality rates (58% vs. 22%, p<0.001 and 65% vs. 28%, p<0.001 respectively). ST-segment depression and RBBB were not associated with either outcome. 63% of bundle branch blocks (RBBB or LBBB) on the presenting ECG resolved by 24-48 hours. In conclusion, compared with ACS patients without cardiac arrest, those with OHCA had higher rates of ST-segment elevation, LBBB and RBBB on admission. Among OHCA patients, ST-segment elevation was associated with lower in-hospital mortality, while LBBB was associated with higher in-hospital and 6-month mortality

GRACE risk score: sex-based validity of in-hospital mortality prediction in Canadian patients with acute coronary syndrome

Background: Although there are sex differences in management and outcome of acute coronary syndromes (ACS), sex is not a component of Global Registry of Acute Coronary Events (GRACE) risk score (RS) for in-hospital mortality prediction. We sought to determine the prognostic utility of GRACE RS in men and women, and whether its predictive accuracy would be augmented through sex-based modification of its components. Methods: Canadian men and women enrolled in GRACE and Canadian Registry of Acute Coronary Events were stratified as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS (NSTE-ACS). GRACE RS was calculated as per original model. Discrimination and calibration were evaluated using the c-statistic and Hosmer-Lemeshow goodness-of-fit test, respectively. Multivariable logistic regression was undertaken to assess potential interactions of sex with GRACE RS components. Results: For the overall cohort (n = 14,422), unadjusted in-hospital mortality rate was higher in women than men (4.5% vs. 3.0%, p < 0.001). Overall, GRACE RS c-statistic and goodness-of-fit test p-value were 0.85 (95%CI 0.83–0.87) and 0.11, respectively. While the RS had excellent discrimination for all subgroups (c-statistics > 0.80), discrimination was lower for women compared to men with STEMI [0.80 (0.75–0.84) vs. 0.86 (0.82–0.89), respectively, p < 0.05]. The goodness-of-fit test showed good calibration for women (p = 0.86), but suboptimal for men (p = 0.031). No significant interaction was evident between sex and RS components (all p > 0.25). Conclusions: The GRACE RS is a valid predictor of in-hospital mortality for both men and women with ACS. The lack of interaction between sex and RS components suggests that sex-based modification is not required

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Mitotic Illegitimate Recombination Is a Mechanism for Novel Changes in High-Molecular-Weight Glutenin Subunits in Wheat-Rye Hybrids

Wide hybrids can have novel traits or changed expression of a quantitative trait that their parents do not have. These phenomena have long been noticed, yet the mechanisms are poorly understood. High-molecular-weight glutenin subunits (HMW-GS) are seed storage proteins encoded by Glu-1 genes that only express in endosperm in wheat and its related species. Novel HMW-GS compositions have been observed in their hybrids. This research elucidated the molecular mechanisms by investigating the causative factors of novel HMW-GS changes in wheat-rye hybrids. HMW-GS compositions in the endosperm and their coding sequences in the leaves of F1 and F2 hybrids between wheat landrace Shinchunaga and rye landrace Qinling were investigated. Missing and/or additional novel HMW-GSs were observed in the endosperm of 0.5% of the 2078 F1 and 22% of 36 F2 hybrid seeds. The wildtype Glu-1Ax null allele was found to have 42 types of short repeat sequences of 3-60 bp long that appeared 2 to 100 times. It also has an in-frame stop codon in the central repetitive region. Analyzing cloned allele sequences of HMW-GS coding gene Glu-1 revealed that deletions involving the in-frame stop codon had happened, resulting in novel ∼1.8-kb Glu-1Ax alleles in some F1 and F2 plants. The cloned mutant Glu-1Ax alleles were expressed in Escherichia coli, and the HMW-GSs produced matched the novel HMW-GSs found in the hybrids. The differential changes between the endosperm and the plant of the same hybrids and the data of E. coli expression of the cloned deletion alleles both suggested that mitotic illegitimate recombination between two copies of a short repeat sequence had resulted in the deletions and thus the changed HMW-GS compositions. Our experiments have provided the first direct evidence to show that mitotic illegitimate recombination is a mechanism that produces novel phenotypes in wide hybrids

Regulation of mTORC1 Signaling by pH

BACKGROUND: Acidification of the cytoplasm and the extracellular environment is associated with many physiological and pathological conditions, such as intense exercise, hypoxia and tumourigenesis. Acidification affects important cellular functions including protein synthesis, growth, and proliferation. Many of these vital functions are controlled by mTORC1, a master regulator protein kinase that is activated by various growth-stimulating signals and inactivated by starvation conditions. Whether mTORC1 can also respond to changes in extracellular or cytoplasmic pH and play a role in limiting anabolic processes in acidic conditions is not known. METHODOLOGY/FINDINGS: We examined the effects of acidifying the extracellular medium from pH 7.4 to 6.4 on human breast carcinoma MCF-7 cells and immortalized mouse embryo fibroblasts. Decreasing the extracellular pH caused intracellular acidification and rapid, graded and reversible inhibition of mTORC1, assessed by measuring the phosphorylation of the mTORC1 substrate S6K. Fibroblasts deleted of the tuberous sclerosis complex TSC2 gene, a major negative regulator of mTORC1, were unable to inhibit mTORC1 in acidic extracellular conditions, showing that the TSC1-TSC2 complex is required for this response. Examination of the major upstream pathways converging on the TSC1-TSC2 complex showed that Akt signaling was unaffected by pH but that the Raf/MEK/ERK pathway was inhibited. Inhibition of MEK with drugs caused only modest mTORC1 inhibition, implying that other unidentified pathways also play major roles. CONCLUSIONS: This study reveals a novel role for the TSC1/TSC2 complex and mTORC1 in sensing variations in ambient pH. As a common feature of low tissue perfusion, low glucose availability and high energy expenditure, acidic pH may serve as a signal for mTORC1 to downregulate energy-consuming anabolic processes such as protein synthesis as an adaptive response to metabolically stressful conditions