Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

<p>Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.</p> <p>Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.</p> <p>Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.</p> <p>Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</p&gt

Dairy consumption and cardiometabolic diseases: systematic review and updated meta-analyses of prospective cohort studies

Purpose of Review Dairy products contain both beneficial and harmful nutrients in relation to cardiometabolic diseases. Here, we provide the latest scientific evidence regarding the relationship between dairy products and cardiometabolic diseases by reviewing the literature and updating meta-analyses of observational studies. Recent Findings We updated our previous meta-analyses of cohort studies on type 2 diabetes, coronary heart disease (CHD), and stroke with nine studies and confirmed previous results. Total dairy and low-fat dairy (per 200 g/d) were inversely associated with a 3–4% lower risk of diabetes. Yogurt was non-linearly inversely associatedwith diabetes (RR = 0.86, 95%CI: 0.83–0.90 at 80 g/ d). Total dairy and milk were not associated with CHD (RR~1.0). An increment of 200 g of daily milk intake was associated with an 8% lower risk of stroke. Summary The latest scientific evidence confirmed neutral or beneficial associations between dairy products and risk of cardiometabolic diseases

Discovery of anaerobic lithoheterotrophic haloarchaea, ubiquitous in hypersaline habitats

Hypersaline anoxic habitats harbour numerous novel uncultured archaea whose metabolic and ecological roles remain to be elucidated. Until recently, it was believed that energy generation via dissimilatory reduction of sulfur compounds is not functional at salt saturation conditions. Recent discovery of the strictly anaerobic acetotrophic Halanaeroarchaeum compels to change both this assumption and the traditional view on haloarchaea as aerobic heterotrophs. Here we report on isolation and characterization of a novel group of strictly anaerobic lithoheterotrophic haloarchaea, which we propose to classify as a new genus Halodesulfurarchaeum. Members of this previously unknown physiological group are capable of utilising formate or hydrogen as electron donors and elemental sulfur, thiosulfate or dimethylsulfoxide as electron acceptors. Using genome-wide proteomic analysis we have detected the full set of enzymes required for anaerobic respiration and analysed their substrate-specific expression. Such advanced metabolic plasticity and type of respiration, never seen before in haloarchaea, empower the wide distribution of Halodesulfurarchaeum in hypersaline inland lakes, solar salterns, lagoons and deep submarine anoxic brines. The discovery of this novel functional group of sulfur-respiring haloarchaea strengthens the evidence of their possible role in biogeochemical sulfur cycling linked to the terminal anaerobic carbon mineralisation in so far overlooked hypersaline anoxic habitats.</p

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008±2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. Results 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/ HDL-Cholesterol: 8.94, 15.09, 6.92. Conclusions In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers

Assessing the evolution of primary healthcare organizations and their performance (2005-2010) in two regions of Québec province: Montréal and Montérégie

<p>Abstract</p> <p>Background</p> <p>The Canadian healthcare system is currently experiencing important organizational transformations through the reform of primary healthcare (PHC). These reforms vary in scope but share a common feature of proposing the transformation of PHC organizations by implementing new models of PHC organization. These models vary in their performance with respect to client affiliation, utilization of services, experience of care and perceived outcomes of care.</p> <p>Objectives</p> <p>In early 2005 we conducted a study in the two most populous regions of Quebec province (Montreal and Montérégie) which assessed the association between prevailing models of primary healthcare (PHC) and population-level experience of care. The <b>goal </b>of the present research project is to track the <it>evolution </it>of PHC organizational models and their relative performance through the reform process (from 2005 until 2010) and to assess factors at the organizational and contextual levels that are associated with the transformation of PHC organizations and their performance.</p> <p>Methods/Design</p> <p>This study will consist of three interrelated surveys, hierarchically nested. The first survey is a population-based survey of randomly-selected adults from two populous regions in the province of Quebec. This survey will assess the current affiliation of people with PHC organizations, their level of utilization of healthcare services, attributes of their experience of care, reception of preventive and curative services and perception of unmet needs for care. The second survey is an organizational survey of PHC organizations assessing aspects related to their vision, organizational structure, level of resources, and clinical practice characteristics. This information will serve to develop a taxonomy of organizations using a mixed methods approach of factorial analysis and principal component analysis. The third survey is an assessment of the organizational context in which PHC organizations are evolving. The five year prospective period will serve as a natural experiment to assess contextual and organizational factors (in 2005) associated with migration of PHC organizational models into new forms or models (in 2010) and assess the impact of this evolution on the performance of PHC.</p> <p>Discussion</p> <p>The results of this study will shed light on changes brought about in the organization of PHC and on factors associated with these changes.</p

Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies

Abstract Background Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract development, leading to a severe, lifelong disease. In this review, what is presently known regarding BPD pathogenesis, its impact on long-term pulmonary morbidity and mortality and the available preventive and therapeutic strategies are discussed. Main body Bronchopulmonary dysplasia is associated with persistent lung impairment later in life, significantly impacting health services because subjects with BPD have, in most cases, frequent respiratory diseases and reductions in quality of life and life expectancy. Prematurity per se is associated with an increased risk of long-term lung problems. However, in children with BPD, impairment of pulmonary structures and function is even greater, although the characterization of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment. Prenatal and postnatal preventive measures are extremely important to reduce the risk of BPD. Conclusion Bronchopulmonary dysplasia is a respiratory condition that presently occurs in preterm neonates and can lead to chronic respiratory problems. Although knowledge about BPD pathogenesis has significantly increased in recent years, not all of the mechanisms that lead to lung damage are completely understood, which explains why therapeutic approaches that are theoretically effective have been only partly satisfactory or useless and, in some cases, potentially negative. However, prevention of prematurity, systematic use of nonaggressive ventilator measures, avoiding supraphysiologic oxygen exposure and administration of surfactant, caffeine and vitamin A can significantly reduce the risk of BPD development. Cell therapy is the most fascinating new measure to address the lung damage due to BPD. It is desirable that ongoing studies yield positive results to definitively solve a major clinical, social and economic problem

Autosomal recessive cerebellar ataxias

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia