Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND & AIMS: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. RESULTS: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. CONCLUSIONS: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.
ISSN: 0168-8278

inserm-00872314
http://www.hal.inserm.fr/inserm-00872314
DOI : 10.1016/j.jhep.2013.01.006
PUBMED : 23333450

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
The aim of this study was to test in vitro the efficacy of TAC, an original G-quadruplex ligand, as a potential radiosensitizing agent for glioblastoma multiforme (GBM). Two human radioresistant telomerase-positive GBM cell lines (SF763 and SF767) were analyzed, with and without TAC treatment, for telomere length, cell proliferation, apoptosis, cell-cycle distribution, gene expression, cytogenetic aberrations, clonogenic survival assay, 53BP1 immunofluorescence staining, and γH2AX phosphorylation. We found that low concentrations of TAC (0.5 and 1 μmol/L) inhibited the proliferation of GBM cells in a concentration-dependent manner after only 1 week of treatment, with minimal effects on cell cycle and apoptosis. TAC treatment had no visible effect on average telomere length but modified expression levels of telomere-related genes (hTERT, TRF1, and TRF2) and induced concentration-dependent DNA damage response and dicentric chromosomes. Survival curves analysis showed that exposure to nontoxic, subapoptotic concentrations of TAC enhanced radiation-induced killing of GBM cells. Analysis of DNA repair after irradiation revealed delayed repair kinetics in GBM cells treated with TAC. Furthermore, the combined treatment (TAC and radiation) significantly increased the frequency of chromosomal aberrations as compared with radiation alone. These findings provide the first evidence that exposure to a G4 ligand radiosensitizes human glioblastoma cells and suggest the prospect of future therapeutic applications.
ISSN: 1535-7163

hal-00851184
https://hal.archives-ouvertes.fr/hal-00851184
DOI : 10.1158/1535-7163.MCT-10-0664
PUBMED : 21987532

Éditeur(s) : HAL CCSD Federation of American Society of Experimental Biology
Résumé : International audience
Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8 degrees C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecular mechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockout mouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germ cell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A. D., Lemonnier, L., De Clerck, T., Bokhobza, A., Derouiche, S., Dewailly, E., Slomianny, C., Mauduit, C., Benahmed, M., Roudbaraki, M., Jegou, B., Prevarskaya, N., Bidaux, G. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.
ISSN: 0892-6638

hal-01390973
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390973
DOI : 10.1096/fj.201600257R
PUBMED : 27317670

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? SUMMARY ANSWER: Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. WHAT IS KNOWN ALREADY: Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. STUDY DESIGN, SIZE, DURATION: A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: High PCB levels were associated with an increase of SHBG (P-trend extless 0.01) and AMH (P-trend extless 0.05) and a decrease of fT (P-trend extless 0.05) and AI (P-trend extless 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P extless 0.05) and E2 (P extless 0.01) and a decrease of fT (P extless 0.05) and AI (P extless 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. STUDY FUNDING/COMPETING INTERESTS: The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare
ISSN: 0268-1161

hal-01220641
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01220641
DOI : 10.1093/humrep/dev260
PUBMED : 26493407

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background Experimental evidence suggests that developmental exposure to persistent organic pollutants (POP) and to some non persistent pesticides may disrupt metabolic regulation of glucose metabolism and insulin secretion, and thereby contribute to the current epidemic of obesity and metabolic disorders. Quasi-experimental situations of undernutrition in utero have provided some information. However, the evidence in humans concerning the role of the prenatal environment in these disorders is contradictory, and little is known about long-term outcomes, such as type 2 diabetes, of prenatal exposure. Objectives Our aim was to evaluate the effects of prenatal exposure to POP and organophosphate pesticides on fetal markers of glucose metabolism in a sample of newborns from the Pelagie mother–child cohort in Brittany (France). Methods Dialkylphosphate (DAP) metabolites of organophosphate pesticides were measured in maternal urine collected at the beginning of pregnancy. Cord blood was assayed for polychlorinated biphenyl congener 153 (PCB153), p,p′-dichlorodiphenyl dichloroethene (DDE) and other POP. Insulin and adiponectin were determined in cord blood serum (n=268). Results A decrease in adiponectin and insulin levels was observed with increasing levels of DDE, but only in girls and not boys. Adiponectin levels were not related to the concentrations of other POP or DAP metabolites. Decreasing insulin levels were observed with increasing PCB153 concentrations. Insulin levels increased with DAP urinary levels. Additional adjustment for BMI z-score at birth modified some of these relations. Conclusions Our observations bring support for a potential role of organophosphate pesticides and POP in alterations to glucose metabolism observable at birth
ISSN: 0013-9351

hal-01259218
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218/file/Prenatal%20exposure%20to%20persistent%20organic%20pollutants%20and%20organophosphate%20pesticides%2C%20and%20markers%20of%20glucose%20metabolism%20at%20birth.pdf
DOI : 10.1016/j.envres.2016.01.005

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Liver X Receptors (LXRs) α and β and the Peroxisome Proliferator-Activated Receptor α (PPARα) are transcription factors that belong to class II nuclear receptors. They drive the expression of genes involved in hepatic lipid homeostasis and therefore are important targets for the prevention and treatment of nonalcoholic fatty liver disease (NAFLD). LXRs and PPARα are regulated by endogenous ligands, oxysterols and fatty acid derived molecules, respectively. In the liver, pharmacological activation of LXRs leads to the over-expression of genes involved in de novo lipogenesis, while PPARα is critical for fatty acid catabolism in nutrient deprivation. Even if these two nuclear receptors seemed to play opposite parts, recent studies have highlighted that PPARα also influence the expression of genes involved in fatty acids synthesis. In this study, we used pharmacological approaches and genetically engineered mice to investigate the cross-talk between LXRs and PPARα in the regulation of genes responsible for lipogenesis. We first investigated the effect of T0901317 and fenofibrate, two synthetic agonists of LXRs and PPARα, respectively. As expected, T0901317 and fenofibrate induce expression of genes involved LXR-dependent and PPARα-dependent lipogenic responses. Considering such overlapping effect, we then tested whether LXR agonist may influence PPARα driven response and vice versa. We show that the lack of PPARα does not influence the effects of T0901317 on lipogenic genes expression. However, PPARα deficiency prevents the up-regulation of genes involved in ω-hydroxylation that are induced by the LXR agonist. In addition, over-expression of lipogenic genes in response to fenofibrate is decreased in LXR knockout mice as well as the expression of PPARα target genes involved in fatty acid oxidation. Altogether, our work provides in vivo evidence for a central interconnection between nuclear receptors that drive hepatic lipid metabolism in response to oxysterol and fatty acids.
ISSN: 0300-9084

inserm-00872582
http://www.hal.inserm.fr/inserm-00872582
DOI : 10.1016/j.biochi.2012.09.028
PUBMED : 23063693

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 Elsevier Masson
Résumé : National audience
ISSN: 0985-0562

hal-01505266
https://hal.archives-ouvertes.fr/hal-01505266
DOI : 10.1016/j.nupar.2016.09.077

Éditeur(s) : HAL CCSD
Résumé : National audience
Objectives To define the different stages of spontaneous labour. To determine the indications, modalities of use and the effects of administering synthetic oxytocin. And to describe undesirable maternal and perinatal outcomes associated with the use of synthetic oxytocin. Method A systematic review was carried out by searching Medline database and websites of obstetrics learned societies until March 2016. Results The 1st stage of labor is divided in a latence phase and an active phase, which switch at 5 cm of cervical dilatation. Rate of cervical dilatation is considered as abnormal below 1 cm per 4 hour during the first part of the active phase, and blow 1 cm per 2 hours above 7 cm of dilatation. During the latent phase of the first stage of labor, i.e. before 5 cm of cervical dilatation, it is recommended that an amniotomy not be performed routinely and not to use oxytocin systematically. It is not recommended to expect the active phase of labor to start the epidural analgesia if patient requires it. If early epidural analgesia was performed, the administration of oxytocin must not be systematic. If dystocia during the active phase, an amniotomy is recommended in first-line treatment. In the absence of an improvement within an hour, oxytocin should be administrating. However, in the case of an extension of the second stage beyond 2 hours, it is recommended to administer oxytocin to correct a lack of progress of the presentation. If dynamic dystocia, it is recommended to start initial doses of oxytocin at 2 mUI/min, to respect at least 30 min intervals between increases in oxytocin doses delivered, and to increase oxytocin doses by 2 mUI/min intervals without surpassing a maximum IV flow rate of 20 mUI/min. The reported maternal adverse effects concern uterine hyper-stimulation, uterine rupture and postpartum haemorrhage, and those of neonatal adverse effects concern foetal heart rate anomalies associated with uterine hyper-stimulation, neonatal morbidity and mortality, neonatal jaundice, weak suck/poor breastfeeding latch and autism. Conclusion The widespread use of oxytocin during spontaneous labour must not be considered as simply another inoffensive prescription without any possible deleterious consequences for mother or foetus. Conditions for administering the oxytocin must therefore respect medical protocols. Indications and patient consent have to be report in the medical file. © 2016 Elsevier Masson SAS
Revue Sage - Femme

hal-01467543
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467543
DOI : 10.1016/j.sagf.2016.11.006

Éditeur(s) : HAL CCSD PeerJ
Résumé : International audience
ISSN: 2167-8359

hal-01662581
https://hal-clermont-univ.archives-ouvertes.fr/hal-01662581
DOI : 10.7717/peerj.3973
PUBMED : 29085764

Éditeur(s) : HAL CCSD
Résumé : National audience
Journées Francophones de Nutrition
Marseille, France

hal-01505276
https://hal.archives-ouvertes.fr/hal-01505276

Éditeur(s) : HAL CCSD
Résumé : LPSC14037
Scientific data collected with modern sensors or dedicated detectors exceed very often the perimeter of the initial scientific design. These data are obtained more and more frequently with large material and human efforts. A large class of scientific experiments are in fact unique because of their large scale, with very small chances to be repeated and to superseded by new experiments in the same domain: for instance high energy physics and astrophysics experiments involve multi-annual developments and a simple duplication of efforts in order to reproduce old data is simply not affordable. Other scientific experiments are in fact unique by nature: earth science, medical sciences etc. since the collected data is "time-stamped" and thereby non-reproducible by new experiments or observations. In addition, scientific data collection increased dramatically in the recent years, participating to the so-called "data deluge" and inviting for common reflection in the context of "big data" investigations. The new knowledge obtained using these data should be preserved long term such that the access and the re-use are made possible and lead to an enhancement of the initial investment. Data observatories, based on open access policies and coupled with multi-disciplinary techniques for indexing and mining may lead to truly new paradigms in science. It is therefore of outmost importance to pursue a coherent and vigorous approach to preserve the scientific data at long term. The preservation remains nevertheless a challenge due to the complexity of the data structure, the fragility of the custom-made software environments as well as the lack of rigorous approaches in workflows and algorithms. To address this challenge, the PREDON project has been initiated in France in 2012 within the MASTODONS program: a Big Data scientific challenge, initiated and supported by the Interdisciplinary Mission of the National Centre for Scientific Research (CNRS). PREDON is a study group formed by researchers from different disciplines and institutes. Several meetings and workshops lead to a rich exchange in ideas, paradigms and methods. The present document includes contributions of the participants to the PREDON Study Group, as well as invited papers, related to the scientific case, methodology and technology. This document should be read as a "facts finding" resource pointing to a concrete and significant scientific interest for long term research data preservation, as well as to cutting edge methods and technologies to achieve this goal. A sustained, coherent and long term action in the area of scientific data preservation would be highly beneficial.
http://hal.in2p3.fr/in2p3-00959072

in2p3-00959072
http://hal.in2p3.fr/in2p3-00959072
http://hal.in2p3.fr/in2p3-00959072/document
http://hal.in2p3.fr/in2p3-00959072/file/PREDON_Scientific_Data_Preservation_2014.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25 mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7 mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510 IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women with a threatened late miscarriage and an isolated undilated shortened cervix (<25 mm on ultrasound), cerclage is only indicated for those with a history of either late miscarriage or preterm delivery (Grade A). Among women with a threatened late miscarriage, an isolated undilated shortened cervix (<25 mm on ultrasound) and no uterine contractions, daily treatment with vaginal progesterone up to 34 weeks of gestation is recommended (Grade A). Hysteroscopic section of the septum is recommended for women with a uterine septum and a history of late miscarriage (Grade C). Correction of acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is recommended after three early or late miscarriages (Grade C). Prophylactic cerclage is recommended for women with a history of three late miscarriages or preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin at a preventive dose are recommended for women with obstetric antiphospholipid syndrome (Grade A). Glycaemic levels should be controlled before conception in women with diabetes (Grade A)
ISSN: 0301-2115

hal-01295639
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01295639
DOI : 10.1016/j.ejogrb.2016.02.015
PUBMED : 27039249

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
ISSN: 0022-1899

hal-01123839
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01123839
DOI : 10.1093/infdis/jiv129
PUBMED : 25737560

Éditeur(s) : HAL CCSD
Résumé : International audience
ACIS Annnual International Conference on Computer and Information Science, ICIS'02
Séoul, South Korea

hal-00354674
https://hal.archives-ouvertes.fr/hal-00354674

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVE: To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. DESIGN: Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months. SETTING: University hospitals. PATIENT(S): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (+/-) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. INTERVENTION(S): Semen analyses and aneuploidy study by FISH were performed at each time point. MAIN OUTCOME MEASURE(S): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. RESULT(S): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD +/- radiotherapy or CHOP/MOPP-ABV. After ABVD +/- radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment. CONCLUSION(S): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.
Fertility and sterility

hal-01477204
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477204
DOI : 10.1016/j.fertnstert.2016.10.001
PUBMED : 27810161

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 American Society for Microbiology
Résumé : International audience
Human leishmaniasis are widely spread diseases with different clinical forms caused by about 20 species within the Leishmania genus. Leishmania species identification is relevant for therapeutic management and prognosis, especially for cutaneous and muco-cutaneous forms. Several methods are available to identify Leishmania species from culture, but they have not been standardized for the majority of the currently described species, with the exception of MultiLocus Enzyme Electrophoresis. Moreover, these techniques are expensive, time-consuming and not available in all laboratories. Within the last decade, mass spectrometry (MS) has been adapted for microorganism identification, including Leishmania However, no commercial reference mass spectral database is available. In this study, a reference mass spectral library (MSL) for Leishmania isolates, accessible through a free web-based application (mass spectral identification, MSI), was constructed and tested. It includes mass spectral data for 33 different Leishmania species, including species that infect humans, animals and phlebotomine vectors. Four laboratories on two continents evaluated MSI performance using 268 samples of which 231 were Leishmania strains. All Leishmania strains, but one, were correctly identified at least at the complex level. A risk of species misidentification within the L. donovani, L. guyanensis and L. braziliensis complexes was observed, as already reported with other techniques. The tested application was reliable, with identification results comparable to those obtained with reference methods, but with a more favorable cost-efficiency ratio. This free online identification system relies on a scalable database and can be implemented directly in the user's computers.
ISSN: 0095-1137

hal-01571305
https://hal.archives-ouvertes.fr/hal-01571305
DOI : 10.1128/JCM.00845-17
PUBMED : 28724559

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
ISSN: 0305-7453

hal-01470808
https://hal.archives-ouvertes.fr/hal-01470808
DOI : 10.1093/jac/dkw352
PUBMED : 27609051