Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Abstract Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing

VKORC1 mutation in European populations of Rattus norvegicus with first data for Italy and the report of a new amino acidic substitution

In the Norway rat, Rattus norvegicus, anticoagulant rodenticide resistance is mainly associated with mutations in the third exon of the Vitamin K epoxide reductase complex subunit 1 (VKORC1). Identification of the resistant wild populations is very important to improve the control practices and to limit the damages due to inadequate use of the anticoagulant rodenticide. In this study, we determined the distribution of the third exon mutations in poorly investigated areas of Africa, Europe and the Middle East. In particular, we investigated the phenomenon for the first time in the Italian peninsula. We obtained sequences of the third exon for 133 Norway rats from 37 localities in Africa, Europe and the Middle East. For additional analysis, we retrieved information in literature on amino acid substitution in 1136 third exon sequences of Norway rats from Europe, the Far East, North America and South America. However, we found third exon mutations only in Europe and the Far East with the Y139F mutation shared between the two areas. Europe has the higher number of mutant individuals and Y139C mutation prevails. In Italy, we found a single missense mutation (I123S) in a Venetian locality. This homozygote mutation, is not know in literature to be associated with resistance, but it is very similar to a mutation that confers resistance in humans (I123N). This similarity and its high local frequency makes it a good candidate for future testing. Our results provide useful data to better understand the resistance phenomenon and to plan targeted control actions

Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene

<p>Abstract</p> <p>Background</p> <p>DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD). Various mutations in the <it>DJ-1 </it>(<it>PARK7</it>) gene have been shown to cause the autosomal recessive form of PD. In the present study South African PD patients were screened for mutations in <it>DJ-1 </it>and we aimed to investigate the functional significance of a novel 16 bp deletion variant identified in one patient.</p> <p>Methods</p> <p>The possible effect of the deletion on promoter activity was investigated using a Dual-Luciferase Reporter assay. The <it>DJ-1 </it>5'-UTR region containing the sequence flanking the 16 bp deletion was cloned into a pGL4.10-Basic luciferase-reporter vector and transfected into HEK293 and BE(2)-M17 neuroblastoma cells. Promoter activity under hydrogen peroxide-induced oxidative stress conditions was also investigated. Computational (<it>in silico</it>) <it>cis</it>-regulatory analysis of <it>DJ-1 </it>promoter sequence was performed using the transcription factor-binding site database, TRANSFAC via the PATCH™ and rVISTA platforms.</p> <p>Results</p> <p>A novel 16 bp deletion variant (g.-6_+10del) was identified in <it>DJ-1 </it>which spans the transcription start site and is situated 93 bp 3' from a Sp1 site. The deletion caused a reduction in luciferase activity of approximately 47% in HEK293 cells and 60% in BE(2)-M17 cells compared to the wild-type (<it>P </it>< 0.0001), indicating the importance of the 16 bp sequence in transcription regulation. The activity of both constructs was up-regulated during oxidative stress. Bioinformatic analysis revealed putative binding sites for three transcription factors AhR, ARNT, HIF-1 within the 16 bp sequence. The frequency of the g.-6_+10del variant was determined to be 0.7% in South African PD patients (2 heterozygotes in 148 individuals).</p> <p>Conclusion</p> <p>This is the first report of a functional <it>DJ-1 </it>promoter variant, which has the potential to influence transcript stability or translation efficiency. Further work is necessary to determine the extent to which the g.-6_+10del variant affects the normal function of the <it>DJ-1 </it>promoter and whether this variant confers a risk for PD.</p

Prevalence and association of asthma and allergic sensitization with dietary factors in schoolchildren: data from the french six cities study

International audienceBackground: The prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study. Methods: Cross-sectional studies were performed among 7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Creteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions. Results: Asthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47-3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the dietary factors was associated with BHR. Conclusions: Diet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy

Taking Action Together: A YMCA-based protocol to prevent Type-2 Diabetes in high-BMI inner-city African American children

<p>Abstract</p> <p>Background</p> <p>Associated with a tripling in obesity since 1970, type 2 diabetes mellitus (T2DM) in children has risen 9-10 fold. There is a critical need of protocols for trials to prevent T2DM in children.</p> <p>Methods/Design</p> <p>This protocol includes the theory, development, evaluation components and lessons learned from a novel YMCA-based T2DM prevention intervention designed specifically for high-BMI African American children from disadvantaged, inner-city neighborhoods of Oakland, California. The intervention was developed on the basis of: review of epidemiological and intervention studies of pediatric T2DM; a conceptual theory (social cognitive); a comprehensive examination of health promotion curricula designed for children; consultation with research, clinical experts and practitioners and; input from community partners. The intervention, <it>Taking Action Together</it>, included culturally sensitive and age-appropriate programming on: healthy eating; increasing physical activity and, improving self esteem.</p> <p>Discussion</p> <p>Evaluations completed to date suggest that <it>Taking Action Together </it>may be an effective intervention, and results warrant an expanded evaluation effort. This protocol could be used in other community settings to reduce the risk of children developing T2DM and related health consequences.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT01039116.</p

Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.Peer reviewe