Éditeur(s) : Caribbean Volunteer Expeditions Caribbean Volunteer Expeditions ( Corning, NY )

Droits : All rights reserved by the source institution.

Éditeur(s) : Caribbean Volunteer Expeditions Caribbean Volunteer Expeditions ( Corning, NY )

Droits : All rights reserved by the source institution.

Éditeur(s) : Caribbean Volunteer Expeditions Caribbean Volunteer Expeditions ( Corning, NY )

Droits : All rights reserved by the source institution.

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This study addresses the mechanical and chemical behavior of allanite during shear zone formation under high-pressure metamorphism. Understanding physico-chemical processes related to the retention or resetting of Pb isotopes in allanite during geological processes is essential for robust petrochronology. Dating of allanite in meta-granodiorite showing variable amounts of strain (from an undeformed protolith to mylonite) at Monte Mucrone (Sesia Zone, NW Italy) gave surprising results. Based on structural and petrographic observations the shear zones at Mt Mucrone are Alpine, yet allanite located within an eclogite facies mylonite yielded Permian ages (208Pb/232Th average age: 287 ± 7 Ma). These mm-sized allanite grains are rimmed by an aggregate of coarse-grained garnet + phengite, thought to derive from former epidote. These aggregates were immersed in a weak matrix that experienced granular flow, and they were thus chemically and mechanically shielded during Alpine mylonitization. In undeformed samples (8a and 8b), two populations of epidote group minerals were found. Allanite forms either coronas around Permian monazite or individual grains with patchy zoning. Both types yield Permian ages (208Pb/232Th age: 291 ± 5 Ma). On the other hand, grains of REE-rich clinozoisite of Cretaceous age are found in undeformed rocks. These grains appear as small fragments with embayed surface outlines and minute satellites or rims around Permian allanite. These (re)crystallized grains are Sr-rich and show mosaic zoning. These results indicate that allanite crystals retained their chemical and isotopic characteristics, and thus their Permian age, as a result of strong strain partitioning between the epidote group porphyroclasts and the eclogite facies matrix in HP-mylonites. The observed partial mobilization of Pb isotopes, which lead to the Cretaceous-aged rims or grains in undeformed samples was facilitated by (re)crystallization of allanite and not by mere Pb diffusion alone under the HP conditions.
ISSN: 0024-4937

insu-00679730
https://hal-insu.archives-ouvertes.fr/insu-00679730
DOI : 10.1016/j.lithos.2011.01.005

Éditeur(s) : HAL CCSD BioMed Central
Résumé : ICARE Study Group
International audience
BackgroundPopulation attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Few studies estimated the PARs of oral cavity cancer to tobacco smoking alone, alcohol drinking alone and their joint consumption but none performed analysis stratified by subsite, gender or age. Among the suspected risk factors of oral cavity cancer, only PAR to a family history of head and neck cancer was reported in two studies. The purpose of this study was to estimate in France the PARs of oral cavity cancer to several recognized and suspected risk factors, overall and by subsite, gender and age.MethodsWe analysed data from 689 oral cavity cancer cases and 3481 controls included in a population-based case–control study, the ICARE study. Unconditional logistic regression models were used to estimate odds ratios (ORs), PARs and 95 % confidence intervals (95 % CI).ResultsThe PARs were 0.3 % (95 % CI −3.9 %; +3.9 %) for alcohol alone, 12.7 % (6.9 %–18.0 %) for tobacco alone and 69.9 % (64.4 %–74.7 %) for their joint consumption. PAR to combined alcohol and tobacco consumption was 74 % (66.5 %–79.9 %) in men and 45.4 % (32.7 %–55.6 %) in women. Among suspected risk factors, body mass index 2 years before the interview <25 kg.m−2, never tea drinking and family history of head and neck cancer explained 35.3 % (25.7 %–43.6 %), 30.3 % (14.4 %–43.3 %) and 5.8 % (0.6 %–10.8 %) of cancer burden, respectively. About 93 % (88.3 %–95.6 %) of oral cavity cancers were explained by all risk factors, 94.3 % (88.4 %–97.2 %) in men and only 74.1 % (47.0 %–87.3 %) in women.ConclusionOur study emphasizes the role of combined tobacco and alcohol consumption in the oral cavity cancer burden in France and gives an indication of the proportion of cases attributable to other risk factors. Most of oral cavity cancers are attributable to concurrent smoking and drinking and would be potentially preventable through smoking or drinking cessation. If the majority of cases are explained by recognized or suspected risk factors in men, a substantial number of cancers in women are probably due to still unexplored factors that remain to be clarified by future studies.
ISSN: 1471-2407

Droits : http://creativecommons.org/licenses/by/
hal-01258466
http://hal.upmc.fr/hal-01258466
http://hal.upmc.fr/hal-01258466/document
http://hal.upmc.fr/hal-01258466/file/BMCC.pdf
DOI : 10.1186/s12885-015-1841-5

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In Western Mediterranean, the Rif belt in Morocco is part of the Gibraltar Arc built during the Tertiary in the framework of Eurasia-Africa convergence. The structural and metamorphic evolution of the internal units of this belt as well as their timing, crucial to constrain the geodynamic evolution of the Alboran Sea, is still largely debated.Our study on the Ceuta Peninsula (Northern Rif) provides new structural, petrological and geochronological data (U-Th-Pb, Ar-Ar), which allow to precise the tectono-metamorphic evolution of the Lower Sebtides metamorphic units with:(1) a syn-metamorphic thrusting event developed under granulite facies conditions (7–10 kbar and 780–820 °C). A major thrust zone, the Ceuta Shear Zone, drove the emplacement of metapelites and peridotitic lenses from the Ceuta Upper Unit over the orthogneisses of the Monte Hacho Lower Unit. This compressional event ended during the Upper Oligocene.(2) an extensional event developed at the boundary between amphibolite and greenschist facies conditions (400–550 °C and 1–3 kbar). During this event, the Ceuta Shear Zone has been reactivated as a normal fault. Normal ductile shear zones contributed to the final exhumation of the metamorphic units during the Early Miocene.We propose that the compressional event is related to the formation of an orogenic wedge located in the upper plate, in a backward position, of the subduction zone driving the geodynamic evolution of the Alboran domain. In this context, the episode of lithospheric thinning could be related to the opening of the Alboran basin in a back-arc position.Furthermore, unlike the previous models proposed for the Rif belt, the tectonic coupling between mantle peridotites and crustal metamorphic rocks occurred in Ceuta Peninsula at a depth of 20–30 km under high temperature conditions, before the extensional event, and thus cannot be related to the back-arc extension.
ISSN: 0040-1951

insu-01682810
https://hal-insu.archives-ouvertes.fr/insu-01682810
DOI : 10.1016/j.tecto.2017.11.028

Éditeur(s) : HAL CCSD
Résumé : International audience
New guidelines have been produced by the CNSF and the CNGOF regarding the use of oxytocin after spontaneous onset of labor in France. This clinical practices were designed to redefine the normal and abnormal obstetrical labor; specify the indications, dosage, procedures, and effects of oxytocin administration; and describe the adverse maternal and perinatal effect associated with oxytocin administration.
31st International Confederation of Midwives (ICM) trienal congress
Toronto, France

Droits : http://creativecommons.org/licenses/by-nc/
hal-01564458
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01564458
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01564458/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01564458/file/Poster%20CNSF%20pour%20ICM%20Toronto%20-%20Juin%202017.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis. © 2016 Rognon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN: 1932-6203

hal-01367148
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367148
DOI : 10.1371/journal.pone.0160888

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
Saccharopolyspora rectivirgula is the principal cause of farmer's lung disease (FLD). Serodiagnosis is based on immunoprecipitation techniques or enzyme immunoassays with homemade crude antigens and is not standardized. We aimed to produce specific recombinant antigens for the development of a standardized ELISA. We recruited 41 patients and 43 healthy exposed controls from five university hospital pneumology departments in France and Switzerland. S. rectivirgula proteins were extracted, separated by 2D electrophoresis, and subjected to Western blotting, with sera from FLD patients or controls. FLD-specific proteins were identified by MS and were produced as recombinant antigens. The diagnostic performance of ELISA tests using the recombinant antigens was assessed with all the sera from FLD patients and controls. We identified 25 FLD-specific proteins, some of which play important roles in transport, nutrition, or virulence. We produced 17 of these proteins as recombinant antigens and assessed their suitability for inclusion in the ELISA test. A combination of three of these proteins (SR1FA, SR17, and SR22) proved remarkably effective at discriminating between patients and controls, with a sensitivity of 83% and a specificity of 77%. The recombinant antigens produced in this study constitute a major step toward the improvement of diagnostic performance and the standardization of FLD serodiagnosis.
ISSN: 1862-8346

hal-01115880
https://hal.archives-ouvertes.fr/hal-01115880
DOI : 10.1002/prca.201400024
PUBMED : 25264606

Éditeur(s) : HAL CCSD
Résumé : International audience
INTRODUCTION: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by imaging features consisting of the association of centrilobular and/or paraseptal emphysema and pulmonary fibrosis. Virtually all patients are smokers and thus at high risk of developing lung cancer. METHODS: This retrospective multicentre study was conducted by the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). RESULTS: A total of 47 patients presenting with lung cancer and CPFE syndrome were identified. All patients were smokers, with a mean of 47 pack-years. A pathological diagnosis of lung cancer was obtained for 38 (81%) patients. Histological type was squamous cell carcinoma in 17 (36%) patients, adenocarcinoma in 14 (30%), non-small-cell lung cancer not otherwise specified in three (6%), small-cell lung cancer in three (6%), and sarcomatoid carcinoma in one (2%). Overall, 20 of the 47 patients could not receive standard-of-care treatment for lung cancer, as per international recommendations or guidelines; this limitation was considered to be directly related to the CPFE syndrome in eight (40%) cases. CONCLUSION: Lung cancer in patients with CPFE syndrome represents a specific entity with a poor prognosis, that further represents the most characteristic and severe model of tobacco-related disease.
Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer

hal-01063912
https://hal.archives-ouvertes.fr/hal-01063912
DOI : 10.1097/JTO.0000000000000209
PUBMED : 25157769

Éditeur(s) : HAL CCSD
Résumé : International audience
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.
European Respiratory Journal

hal-01647080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647080
DOI : 10.1183/13993003.00716-2017
PUBMED : 29074543

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Convergent plate margins typically experience a transition from subduction to collision dynamics as massive continental blocks enter the subduction channel. Studies of high-pressure rocks indicate that tectonic fragments are rapidly exhumed from eclogite facies to mid-crustal levels, but the details of such dynamics are controversial. To understand the dynamics of a subduction channel we report the results of a petrochronological study from the central Sesia Zone, a key element of the internal Western Alps. This comprises two polymetamorphic basement complexes (Eclogitic Micaschist Complex and Gneiss Minuti Complex) and a thin, dismembered cover sequence (Scalaro Unit) associated with pre-Alpine metagabbros and metasediments (Bonze Unit). Structurally controlled samples from three of these units (Eclogitic Micaschist Complex and Scalaro-Bonze Units) yield unequivocal petrological and geochronological evidence of two distinct high-pressure stages. Ages (U-Th-Pb) of growth zones in accessory allanite and zircon, combined with inclusion and textural relationships, can be tied to the multi-stage evolution of single samples. Two independent tectono-metamorphic 'slices' showing a coherent metamorphic evolution during a given time interval have been recognized: the Fondo slice (which includes Scalaro and Bonze rocks) and the Druer slice (belonging to the Eclogitic Micaschist Complex). The new data indicate separate stages of deformation at eclogite-facies conditions for each recognized independent kilometer-sized tectono-metamorphic slice, between ∼85 and 60 Ma, with evidence of intermittent decompression (ΔP ∼ 0*5 GPa) within only the Fondo slice. The evolution path of the Druer slice indicates a different P-T-time evolution with prolonged eclogite-facies metamorphism between ∼85 and 75 Ma. Our approach, combining structural, petrological and geochronological techniques, yields field-based constraints on the duration and rates of dynamics within a subduction channel.
ISSN: 0022-3530

hal-01054335
https://hal.archives-ouvertes.fr/hal-01054335
DOI : 10.1093/petrology/egu029

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Subcutaneous fat tissues from an indigenous fat-type breed and an intensively-lean selected breed were studied in juvenile pigs. Combining DIGE with bioinformatics and target analyses of key genes, enzymes or terminal routes, this study identifies metabolic and homeostatic processes, response to organic substances, and acute-phase responses as the main pathways whose proteins were regulated in association with adiposity. Breed-related differences in abundance and activities of malic enzyme and glucose-6-phosphate dehydrogenase NADPH-supplying enzymes suggested up-regulation of the lipogenic pathway to dispose for a greater adiposity. Over-abundance in the lipolytic protein carboxylesterase-1 was revealed in fat-type piglets. A panel of pro- and anti-inflammatory proteins such as serpins, had an altered abundance in the fat-type piglets, suggesting adverse consequences of fat accumulation even in early post-weaning stages. Propensity to low-grade inflammation in fat pigs was reinforced by the up-regulation of genes encoding pro-inflammatory cytokines IL6 and TNF-α in these piglets. Differential abundance in annexin-A5 and pericentrin suggested a positive regulation of cell apoptosis in lean piglets. Our results are relevant in the context of data linking the accretion of body lipids to the physiology and pathology of adipose tissue in models other than rodents for a better control of human health and nutrition.
ISSN: 1874-3919

hal-01122161
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122161
PUBMED : 22061664
DOI : 10.1016/j.jprot.2011.10.012

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Contexte La qualité de l’air ambiant dans les enceintes de transports ferroviaires souterrains (EFS) est caractérisée par des particules en suspension riches en métaux, majoritairement du fer, et en carbone, dont la concentration massique est très supérieure à celle mesurée dans l’air ambiant extérieur aux EFS. Cependant, les risques sanitaires chez les travailleurs des EFS liés aux polluants chimiques de l’air présents dans ces enceintes ferroviaires ont été peu étudiés. Dans ce contexte, l’Anses a été saisie afin de dresser un état des connaissances et réaliser une évaluation des risques sanitaires (ERS) chez les travailleurs des EFS. Méthodes Un groupe de travail pluridisciplinaire a analysé les études publiées jusqu’en décembre 2014 et des données communiquées par les exploitants de transport. L’ERS a porté sur les travailleurs de l’exploitation, l’organisation du transport et des services, et des commerces qui exercent une activité durant les horaires de trafic des rames de voyageurs. L’exposition chronique des travailleurs a été estimée à partir des données de concentration inhalée en particules (PM2,5 et PM10), en éléments métalliques, en carbone, en hydrocarbures aromatiques polycycliques particulaires et en hydrocarbures aromatiques monocycliques, issues d’une campagne transversale de métrologie individuelle de la RATP. Cette exposition estimée a ensuite été comparée à une valeur toxicologique de référence (VTR ajustée, VLEP, NOAECHEC) pour calculer un indicateur de risque. Résultats Les risques sanitaires en lien avec les éléments métalliques évalués individuellement semblent négligeables. Concernant l’exposition chronique aux particules, une inflammation des voies respiratoires et des effets consécutifs à cette inflammation sont probables, sur la base d’un effet démontré par une étude de toxicité aiguë chez l’animal. Par analogie avec les particules de l’air ambiant extérieur, des effets délétères sont attendus sur la santé cardiovasculaire et respiratoire en lien avec l’exposition chronique de ces travailleurs aux particules des EFS. L’ERS présente néanmoins des incertitudes notables compte tenu notamment du corpus d’études épidémiologiques assez peu informatif et de l’absence d’étude toxicologique d’exposition chronique. Conclusion Des effets sanitaires sont attendus en relation avec l’exposition chronique des travailleurs à la pollution de l’air des EFS. Des travaux sont recommandés pour combler les lacunes des connaissances sur la toxicité à long terme des particules de l’air de ces enceintes ferroviaires, mais également sur l’exposition de certaines catégories de travailleurs de la maintenance vraisemblablement plus exposés
ISSN: 1775-8785

hal-01331986
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01331986
DOI : 10.1016/j.admp.2016.03.448
PUBMED : 26334607

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.
ISSN: 1932-6203

hal-01368315
https://hal.archives-ouvertes.fr/hal-01368315
DOI : 10.1371/journal.pone.0160888
PUBMED : 27490813
PUBMEDCENTRAL : PMC4973876

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (>/=F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
Journal of gastroenterology and hepatology

hal-01477209
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477209
DOI : 10.1111/jgh.13338
PUBMED : 26992056

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. OBJECTIVES: The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. METHODS: We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case-control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. RESULTS: After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. CONCLUSIONS: Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk
ISSN: 1351-0711

hal-01282444
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282444
DOI : 10.1136/oemed-2015-103177
PUBMED : 26911986

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Mantle cell lymphoma (MCL) is a hematologic neoplasm characterised by the t(11;14)(q13;q32) translocation leading to aberrant cyclin D1 expression. The cell functions of cyclin D1 depend on its partners and/or subcellular distribution, resulting in different oncogenic properties. We observed the accumulation of cyclin D1 in the cytoplasm of a subset of MCL cell lines and primary cells. In primary cells, this cytoplasmic distribution was correlated with a more frequent blastoid phenotype. We performed immunoprecipitation assays and mass spectrometry on enriched cytosolic fractions from two cell lines. The cyclin D1 interactome was found to include several factors involved in adhesion, migration and invasion. We found that the accumulation of cyclin D1 in the cytoplasm was associated with higher levels of migration and invasiveness. We also showed that MCL cells with high cytoplasmic levels of cyclin D1 engrafted more rapidly into the bone marrow, spleen, and brain in immunodeficient mice. Both migration and invasion processes, both in vivo and in vitro, were counteracted by the exportin 1 inhibitor KPT-330, which retains cyclin D1 in the nucleus. Our data reveal a role of cytoplasmic cyclin D1 in the control of MCL cell migration and invasion, and as a true operator of MCL pathogenesis.
ISSN: 2045-2322

hal-01635754
https://hal.archives-ouvertes.fr/hal-01635754
DOI : 10.1038/s41598-017-14222-1
PUBMED : 29066743

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Lung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents. Considering the high proportion of mutant proteins in tumor cells, and the high rate of mutation of the TP53 gene in all cancers, and in NSCLC in particular, this gene is a perfect target. Certain new molecules have been shown to restore the activity of mutated p53 protein, for example PRIMA-1, which reactivates the His273 mutant p53. In a previous study, we presented triazine A190, a molecule with a cytostatic activity that blocks cells in the G1 phase and induces apoptosis. Here, we show that A190 not only restores mutant p53 activity, but also induces an overexpression of the NEDD9 gene, leading to apoptotic death. These findings might offer hope for the development of new targeted therapies, specific to tumor cells, which spare healthy cells
ISSN: 2045-2322

hal-01165439
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165439
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165439/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165439/file/TP53%20transcription%20factor.pdf
DOI : 10.1038/srep10356