Pertinence des venues aux urgences médico-chirurgicales pédiatriques des nouveau-nés de moins de 30 jours à l HCE du CHU de Grenoble sur une période de six mois

Les consultations de nouveau-nés aux urgences pédiatriques sont en augmentation, en dépit du risque d infection nosocomiale encouru. Le ressenti d urgence des parents, et les problèmes de disponibilité des médecins libéraux peuvent expliquer ce phénomène. L objectif principal de ce travail est d apprécier la pertinence des venues des nouveau-nés de moins de 30 jours aux urgences pédiatriques. L étude a été réalisée aux urgences pédiatriques de Grenoble de mai à novembre 2012. 266 nouveau-nés ont été inclus. Seules les premières consultations pour un même nouveau-né ont été prises en compte. La pertinence des venues a été étudiée selon les critères de De Angelis, et selon le critère d hospitalisation. Les venues ont été jugées pertinentes pour 39% des nouveau-nés. Les facteurs associés à une venue jugée non pertinente sont la primiparité, l âge de la mère inférieur à 25 ans, l absence d activité professionnelle de la mère, le temps de transport inférieur à 40 minutes et les nouveau-nés non adressés. Les diagnostics les plus fréquents sont liés à des problèmes de puériculture. Des formations doivent être données dès les premières séances de préparation à l accouchement, auprès des jeunes mamans primipares. Il faudrait également favoriser la consultation du 8ème jour auprès d un médecin de ville après la sortie de la maternité. Des plaquettes d information pour les parents ont été créées par des associations. Cependant, l augmentation des consultations aux urgences pédiatriques pourrait-être liée à une limitation de l offre de soins en ville. Une étude complémentaire serait intéressante pour connaître l offre et la disponibilité des professionnels de santé en ville.The Newborns consultations in the pediatric emergency department have steadily increased during the last years, despite the known risk of nosocomial infection. The main objective of this study is to assess the relevance of the visits for newborns less than one month of age in the pediatric emergency department. This study was carried out in the pediatric emergency department of Grenoble from the 2nd of May 2012 to the 2nd of November 2012, using a questionnaire given to the parents, and a medical questionnaire. The visits relevance was studied according to De Angelis criteria, and according to the hospitalization criterion. 266 infants have been included. The most common diagnoses which have been found are childcare problems such as infant colic, regurgitation, feeding difficulties and rhinopharyngitis. The examination was normal for 25 newborns. Visits were considered relevant for 105 newborns. The factors which were associated with inappropriate visits are: primiparity, age of the mother less than 25 years old, unemployed mothers, travel time less than 40 minutes, and not addressed newborns. Prevention and information should be made in the early sessions of preparation for childbirth. Other preventive measures would be to promote a medical examination by a primary care physician a few days after having left the maternity. Finally, information leaflets for parents were created by associations. The increase of the consultations in the pediatric emergency departments could be related to a limitation of the primary care supply. A further study would be interesting to know the supply and the availability of the health professionals in the city.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

047: Gender difference in mortality after ST-segment elevation myocardial infarction in the Registre d’Infarctus Maine-Anjou (RIMA)

BackgroundA greater mortality in women versus men in ST-segment elevation myocardial infarction (STEMI) is now well documented but remains unexplained.MethodsWe compared outcomes for STEMI in the “Registre d’Infarctus Maine-Anjou” (RIMA) from 2003 to 2009 between men and women.ResultsWe analyzed data from 390 women (29%) and 962 men (71%) admitted for STEMI. Women were older, 72.93±14.21 versus 61.70±14.14 years old (p<0.001) and have more hypertension history (68.7% vs. 43.3%; p<0.001). Women received less percutaneous coronary intervention and thrombolysis than men, respectively 51.5% vs. 64.6% (p<0.001) and 9.5% vs. 22.1% (p<0.001). Admission delay was longer in women. In univariate analysis, in-hospital mortality was higher in women (13.59% vs. 6.13%; p<0.001), post-discharge mortality until one year was also higher in women (8.9% vs. 3.88%; p<0.001). No differences were observed for in-hospital mortality and post-discharge mortality in age-adjusted Odds Ratio (OR) (OR=0.77 [0.5-1.77]; p=0.127 and OR=0.78 [0.45-1.35]; p=0.38 respectively).ConclusionOur study suggests that older age in women explains most of the mortality difference

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the ‘‘time of diagnosis’’ phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation

Genomic diversity evaluation of populus trichocarpa germplasm for rare variant genetic association studies

Genome-wide association studies are powerful tools to elucidate the genome-to-phenomerelationship. In order to explain most of the observed heritability of a phenotypic trait, asufficient number of individuals and a large set of genetic variants must be examined. Thedevelopment of high-throughput technologies and cost-efficient resequencing of completegenomes have enabled the genome-wide identification of genetic variation at large scale.As such, almost all existing genetic variation becomes available, and it is now possible toidentify rare genetic variants in a population sample. Rare genetic variants that were usuallyfiltered out in most genetic association studies are the most numerous genetic variationsacross genomes and hold great potential to explain a significant part of the missingheritability observed in association studies. Rare genetic variants must be identified withhigh confidence, as they can easily be confounded with sequencing errors. In this study,we used a pre-filtered data set of 1,014 purePopulus trichocarpaentire genomes toidentify rare and common small genetic variants across individual genomes. We comparedvariant calls betweenPlatypusandHaplotypeCallerpipelines, and we further applied strictqualityfilters for improved genetic variant identification. Finally, we only retained geneticvariants that were identified by both variant callers increasing calling confidence. Based onthese shared variants and after stringent qualityfiltering, we found high genomic diversity inP. trichocarpagermplasm, with 7.4 million small genetic variants. Importantly, 377k non-synonymous variants (5% of the total) were uncovered. We highlight the importance ofgenomic diversity and the potential of rare defective genetic variants in explaining asignificant portion ofP. trichocarpa's phenotypic variability in association genetics. Theultimate goal is to associate both rare and common alleles with poplar's wood quality traitsto support selective breeding for an improved bioenergy feedstock

Design and validation of a 63K genome-wide SNP-genotyping platform for caribou/reindeer (Rangifer tarandus)

Background Development of large single nucleotide polymorphism (SNP) arrays can make genomic data promptly available for conservation problematic. Medium and high-density panels can be designed with sufficient coverage to offer a genome-wide perspective and the generated genotypes can be used to assess different genetic metrics related to population structure, relatedness, or inbreeding. SNP genotyping could also permit sexing samples with unknown associated metadata as it is often the case when using non-invasive sampling methods favored for endangered species. Genome sequencing of wild species provides the necessary information to design such SNP arrays. We report here the development of a SNP-array for endangered Rangifer tarandus using a multi-platform sequencing approach from animals found in diverse populations representing the entire circumpolar distribution of the species. Results From a very large comprehensive catalog of SNPs detected over the entire sample set (N = 894), a total of 63,336 SNPs were selected. SNP selection accounted for SNPs evenly distributed across the entire genome (~ every 50Kb) with known minor alleles across populations world-wide. In addition, a subset of SNPs was selected to represent rare and local alleles found in Eastern Canada which could be used for ecotype and population assignments - information urgently needed for conservation planning. In addition, heterozygosity from SNPs located in the X-chromosome and genotyping call-rate of SNPs located into the SRY gene of the Y-chromosome yielded an accurate and robust sexing assessment. All SNPs were validated using a high-throughput SNP-genotyping chip. Conclusion This design is now integrated into the first genome-wide commercially available genotyping platform for Rangifer tarandus. This platform would pave the way to future genomic investigation of populations for this endangered species, including estimation of genetic diversity parameters, population assignments, as well as animal sexing from genetic SNP data for non-invasive samples

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Étude de l'adaptation au niveau moléculaire chez l'épinette noire (Picea mariana (Mill.) B.S.P.)

Comprendre les bases génétiques de l'adaptation constitue un objectif important de la biologie évolutive, particulièrement celles reliées aux adaptations au climat, en raison des changements climatiques présents et prédits. Une variation génétique des caractères quantitatifs reliés à l'adaptation selon des gradients géographiques et climatiques a déjà été démontrée chez l'épinette noire (Picea mariana [Mill.] B.S.P.), sans pour autant identifier les variations de l'ADN responsables de ces tendances. Afin de documenter la nature des polymorphismes d'ADN reliés aux adaptations climatiques chez cette espèce, des SNPs (Single Nucleotide Polymorphisms) situés dans des séquences de gènes ont été testés par différentes méthodes, permettant d'identifier des marqueurs ou des régions du génome qui sont sous sélection ou impliqués dans la variation de caractères reliés à l'adaptation. L'étude des niveaux de différenciation génétique entre groupes climatiques de populations pour 583 SNPs de gènes, ayant servi à cartographier le génome de l'espèce, a permis d'identifier 26 polymorphismes reliés à l'adaptation à la température et/ou aux précipitations. Ces SNPs, soumis à une intensité de sélection moyenne mais significative depuis la colonisation postglaciaire, étaient dispersés sur l'ensemble du génome et représentaient une large diversité de familles de gènes dont certaines avaient déjà été relevées dans d'autres études d'adaptation chez les conifères. Des analyses de cartographie de QTL (Quantitative Trait Loci) impliqués dans la variation de la date d'aoûtement ou de la hauteur chez des arbres juvéniles ont également révélé plusieurs régions impliquées dans l'adaptation avec de faibles proportions de variance expliquée par QTL. Par la suite, des tests d'association entre des SNPs candidats et ces caractères ont permis de relier 65% d'entre eux à la variation phénotypique, appuyant leur implication dans l'adaptation. L'étude de la distribution de SNPs neutres à travers l'ensemble de l'aire de répartition de l'épinette noire au Canada a permis d'identifier trois lignées glaciaires et leurs zones de contact. Des analyses d'identification de SNPs reliés à la variation climatique ont été menées indépendamment dans les deux plus grandes lignées glaciaires et ont démontré que l'histoire démographique reliée aux événements glaciaires avait influencé la composition génétique préexistante sur laquelle la sélection naturelle a pu agir ultérieurement

Etude du système dopaminergique par tomographie par émission monophotonique (apport dans le diagnostic précoce des maladies parkinsoniennes)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

CNVs into the wild: screening the genomes of conifer trees (Picea spp.) reveals fewer gene copy number variations in hybrids and links to adaptation

Abstract Background Copy number variations (CNVs) have been linked to different phenotypes in human, including many diseases. A genome-scale understanding of CNVs is available in a few plants but none are wild species, leaving a knowledge gap regarding their genome biology and evolutionary role. We developed a reliable CNV detection method for species lacking contiguous reference genome. We selected multiple probes within 14,078 gene sequences and developed comparative genome hybridization on arrays. Gene CNVs were assessed in three full-sib families from species with 20 Gb genomes, i.e., white and black spruce, and interior spruce\ua0-\ua0a natural hybrid. Results We discovered hundreds of gene CNVs in each species, 3612 in total, which were enriched in functions related to stress and defense responses and narrow expression profiles, indicating a potential role in adaptation. The number of shared CNVs was in accordance with the degree of relatedness between individuals and species. The genetically mapped subset of these genes showed a wide distribution across the genome, implying numerous structural variations. The hybrid family presented significantly fewer CNVs, suggesting that the admixture of two species within one genome reduces the occurrence of CNVs. Conclusions The approach we developed is of particular interest in non-model species lacking a reference genome. Our findings point to a role for CNVs in adaptation. Their reduced abundance in the hybrid may limit genetic variability and evolvability of hybrids. We propose that CNVs make a qualitatively distinct contribution to adaptation which could be important for short term change