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Purpose: Plasma cell-free DNA (cfDNA) genotyping is increasingly used in cancer care, but assay accuracy has been debated. Because most cfDNA is derived from peripheral blood cells (PBC), we hypothesized that nonmalignant mutations harbored by hematopoietic cells (clonal hematopoiesis, CH) could be a cause of false-positive plasma genotyping.Experimental Design: We identified patients with advanced non–small cell lung cancer (NSCLC) with KRAS, JAK2, or TP53 mutations identified in cfDNA. With consent, PBC DNA was tested using droplet digital PCR (ddPCR) or next-generation sequencing (NGS) to test for CH-derived mutations.Results: We first studied plasma ddPCR results from 58 patients with EGFR-mutant NSCLC. Two had KRAS G12X detected in cfDNA, and both were present in PBC, including one where the KRAS mutation was detected serially for 20 months. We then studied 143 plasma NGS results from 122 patients with NSCLC and identified 5 JAK2 V617F mutations derived from PBC. In addition, 108 TP53 mutations were detected in cfDNA; for 33 of the TP53 mutations, PBC and tumor NGS were available for comparison, and 5 were present in PBC but absent in tumor, consistent with CH.Conclusions: We find that most JAK2 mutations, some TP53 mutations, and rare KRAS mutations detected in cfDNA are derived from CH not tumor. Clinicians ordering plasma genotyping must be prepared for the possibility that mutations detected in plasma, particularly in genes mutated in CH, may not represent true tumor genotype. Efforts to use plasma genotyping for cancer detection may need paired PBC genotyping so that CH-derived mutations are not misdiagnosed as occult malignancy. Clin Cancer Res; 24(18); 4437–43. ©2018 AACR.See related commentary by Bauml and Levy, p. 4352

Droplet digital PCR (ddPCR) of the peripheral blood cell DNA from 4 cases with JAK2 V617F found on plasma next-generation sequencing (NGS). In each, the JAK2 mutation was detected (top), consistent with clonal hematopoiesis, while not detected in a control sample.

International audience; Mating type is a critical trait in heterothallic organisms. In plant pathogenic oomycetes, like the late blight pathogen Phytophthora infestans, it is usually identified through pairing between tester and candidate isolates, a method that is both laborious and applicable to live isolates only. Therefore, developing simple and fast PCR tests to reliably identify P. infestans mating types is of great interest for population genetic studies. A multiplex PCR assay combining the amplification of a locus diagnostic for P. infestans and of one diagnostic for the A1 mating type was developed and validated on a collection of 1,441 samples, covering the current and past diversity of European P. infestans populations. These samples were obtained from either freeze-dried mycelium or FTA cards on which diseased leaflets had been pressed. The multiplex assay correctly identified mating types in 97.4% of these samples. The main source of incorrect assignment was the lack of amplification of the A1 diagnostic allele, due to insufficient DNA quality and/or quantity in the reaction mix. This multiplex PCR, applicable to both live and stored material, thus constitutes a useful addition to the set of molecular tools available for population typing in P. infestans.

International audience; Until recently, genotypes of Phytophthora infestans were regionally distributed in Europe, with populations in western Europe being dominated by clonal lineages and those in northern Europe being genetically diverse because of frequent sexual reproduction. However, since 2013 a new clonal lineage (EU_41_A2) has successfully established itself and expanded in the sexually recombining P. infestans populations of northern Europe. The objective of this study was to study phenotypic traits of the new clonal lineage of P. infestans, which may explain its successful establishment and expansion within sexually recombining populations. Fungicide sensitivity, aggressiveness, and virulence profiles of isolates of EU_41_A2 were analyzed and compared with those of the local sexual populations from Denmark, Norway, and Estonia. None of the phenotypic data obtained from the isolates collected from Denmark, Estonia, and Norway independently explained the invasive success of EU_41_A2 within sexual Nordic populations. Therefore, we hypothesize that the expansion of this new genotype could result from a combination of fitness traits and more favorable environmental conditions that have emerged in response to climate change.

International audience; Launched in 1987, the French National Programme for the Conservation of Native Elm Genetic Resources focused on the ex situ conservation of clones of adult field elms (Ulmus minor Mill.) survivors of the Dutch elm disease (DED) pandemic. It was later expanded to include the in situ dynamic conservation of populations of European white elm (U. laevis Pall.) and wych elm (U. glabra Huds.). The national collection contains 441 clones, partly characterized and evaluated in a European project. The pathological tests and experimental plantations did not reveal clones truly resistant to DED but provided material for the restoration of hedgerows. Two conservation units of white elm and one of wych elm were selected, enriching the pan-European EUFORGEN network for dynamic conservation of forest genetic resources. This programme provides feedback on genetic conservation strategies for forest trees in a health crisis. New partners are invited to make use of the scientific potential of the clone bank and experimental plots.

International audience; Objective: Fibroblast Growth Factor 23 ( FGF23) may represent an attractive candidate that could participate to the osteoarthritic ( OA)-induced phenotype switch of chondrocytes. To address this hypothesis, we investigated the expression of FGF23, its receptors ( FGFRs) and co-receptor ( Klotho) in human cartilage and studied the effects of rhFGF23 on OA chondrocytes. Method: Gene expression or protein levels were analysed by RT-PCR and immunohistochemistry. Collagenase 3 ( MMP13) activity was measured by a fluorescent assay. MAPK signalling pathways were investigated by phosphoprotein array, immunoblotting and the use of selective inhibitors. RNA silencing was performed to confirm the respective contribution of FGFR1 and Klotho. Results: We showed that the expression of FGF23, FGFR1 and Klotho was up-regulated at both mRNA and protein levels in OA chondrocytes when compared to healthy ones. These overexpressions were markedly elevated in the damaged regions of OA cartilage. When stimulated with rhFGF23, OA chondrocytes displayed an extended expression of FGF23 and of markers of hypertrophy such as MMP13, COL10A1, and VEGF. We demonstrated that FGF23 auto-stimulation was both FGFR1-and Klotho-dependent, whereas the expression of markers of hypertrophy was mainly dependent on FGFR1 alone. Finally, we showed that FGF23-induced MMP13 expression was strongly regulated by the MEK/ERK cascade and to a lesser extent, by the PI-3K/AKT pathway. Conclusion: These results demonstrate that FGF23 sustains differentiation of OA chondrocytes in a Klotho-independent manner. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

International audience; Ascochyta blight of pea is caused by four related fungi, Ascochyta pisi, Phoma koolunga, Ascochyta pinodes and Ascochyta pinodella. The latter two taxa appear to be much more common and economically significant worldwide but the relative impact of each fungus on ascochyta blight epidemics is not well understood. To study the spatiotemporal distribution of A. pinodes and A. pinodella infecting pea in France, 368 isolates were sampled monthly, from February to May, at three locations (Rennes, Boigneville and Dijon) and molecular markers were used to genotype isolates. The aggressiveness of isolates from the fourth sampling date was estimated using a detached leaf assay on the winter cultivar Enduro. Disease was low during the sampling period as climatic conditions were generally not conducive to disease development (cold temperature, low rainfall). Population genetic analysis showed that 99% of the observed variation could be attributed to variation within populations compared to only 1% among populations. Both species were observed in each location, although A. pinodella was observed at a lower frequency (6–32%). Moreover, results showed that both species could develop on different nodes of the plant. Significant differences in aggressiveness were observed between species and among isolates within species with A. pinodes isolates being significantly more aggressive on average than A. pinodella isolates. These results emphasize the necessity to study the components of disease complexes in order to understand the impact of pathogen species interactions on disease and yield reduction as well as the dynamics of disease epidemics during the cropping season.

Les syndromes d’apnee/hyponee obstructif du sommeil (SAHOS) de l’enfant et de l’adulte presentent d’importantes differences d’un point de vue physio- pathologique et semiologique. La prise en charge therapeutique du SAHOS de l’enfant est specifique. L’orthopedie dento faciale doit detecter les porteurs de SAHOS, les orienter et les prendre en charge au sein d’une equipe pluridisiplinaire. Meme s’il n’existe aucune typologie faciale specifique du SAHOS certaines d’entre elles sont plus suceptibles de voir apparaitre le syndrome. L’endognathie maxillaire, la retrognathie mandibulaire et l’hyperdivergence faciale font partie des typologies a risque. Leur prise en charge precoce avec une therapeutique adaptee doit permettre d’en diminuer le risque.

International audience; Ascochyta blight, caused by the polyphagous fungus Didymella pinodes, is one of the most economically damaging diseases of pea. Susceptibility/resistance of several legume species to several D. pinodes isolates from pea was assessed under controlled environmental conditions to test the hypothesis that D. pinodes was host-specific. Forty-three cultivars of five legume species (pea, common vetch, clover, alfalfa and faba bean) typically grown in temperate climates were screened with four pea-infecting isolates from France, and one pea-infecting isolate from Australia. Seven days after inoculation, disease incidence and necrosis were measured on foliar organs to estimate aggressiveness of the isolates. Cultivars of each legume species displayed differential resistance/susceptibility to each isolate as indicated by significant cultivar 9 isolate interactions in ANOVA. Faba bean, common vetch, alfalfa and clover cultivars were consistently less susceptible than pea cultivars regardless of the inoculated isolate. The behaviour of D. pinodes isolates also indicated various patterns of disease development according to the legume species and the cultivars. Genetic distance between the five legume species was not correlated with overall differences in susceptibility, indicating that D. pinodes is not specialized to pea and shows a wide host range among legume species. Disease risk assessment in the pea crop should therefore consider the vicinity of cultivated and wild legume species that may serve as alternative hosts for D. pinodes.

Resume But de l’etude Le ministere de la Sante et ses agences regionales ont decide le 27 decembre 2010 de developper la chirurgie ambulatoire dans le but avoue de supprimer 48 000 lits de chirurgie en France. Cette evolution, qui provient des pays anglo-saxons, est ineluctable devant le deficit financier de notre assurance maladie. A l’exemple des plasticiens canadiens, qui y ont ete contraints depuis sept ans, nous avons voulu etudier la faisabilite d’une prise en charge ambulatoire des plasties mammaires de reduction dans un service hospitalo-universitaire. Patientes et methodes Entre janvier et juin 2012, 25 patientes, âgees de moins de 65 ans ont ete operees pour une plastie mammaire de reduction programmee en ambulatoire. Aucune ne presentait de risque anesthesique particulier. Toutes residaient a moins d’une heure de l’hopital, sortaient accompagnees, etaient revues le lendemain de l’intervention, puis de facon habituelle. Nos criteres d’evaluation etaient les suivants : satisfaction globale de la prise en charge en ambulatoire, poids de resection glandulaire, complications postoperatoires, taux de readmission. Resultats L’âge moyen des patientes etait de 32 ans (19–56 ans). Le poids de resection moyen etait de 400 g par sein (140–1000 g). Vingt patientes sont sorties le soir meme (80 %). Parmi elles, 19 (95 %) ont exprime leur satisfaction et accepteraient a nouveau cette intervention en ambulatoire. Aucune complication majeure n’est survenue dans cette serie. Les cinq autres patientes ont vu leur sortie repoussee par les anesthesistes pour les motifs suivants : score d’Aldrete inferieur a 9, douleur non soulagee par les antalgiques de palier I ou II, nausees et vomissements incoercibles. Conclusion Cette premiere etude clinique realisee en France, confirme que lorsque certaines conditions sont remplies, les plasties mammaires de reduction peuvent etre realisees en ambulatoire en toute securite. Le taux de satisfaction mesure montre une tres forte adhesion des patientes a la prise en charge en ambulatoire.

Resume Objectif Etudier la qualite de vie des patients traites pour un cancer pharyngolarynge avance avec un traitement preservateur ou avec laryngectomie. Patients et methodes Etude retrospective bicentrique portant sur 100 patients en remission d’un carcinome epidermoide pharyngolarynge, traites entre 1998 et 2009. Soixante-dix patients ont ete traites par pharyngolaryngectomie totale suivie de radiotherapie externe (24 hypopharynx, 46 larynx) et 30 patients ont eu un protocole de preservation d’organe (13 hypopharynx, 17 larynx) qui etait soit une radio-chimiotherapie concomitante, soit une chimiotherapie d’induction par platine-5FU ou taxane–platine-5FU suivie de radiotherapie. Tous les patients ont repondu aux questionnaires de qualite de vie (EORTC QLQ-C30 et QLQ-HN larynx : 72,4 % vs 37,5 % p p p = ns). Pour les cancers larynges, la seule difference significative concernait l’item « secheresse buccale » moins invalidante apres traitement chirurgical ( p Conclusion La qualite de vie est degradee chez tous les patients traites pour un cancer pharyngolarynge. Les traitements, preservateurs ou non, alterent de maniere differente les divers aspects de la qualite de vie.

Resume Une septicemie nosocomiale a Enterobacter cloacae est survenue au 21e jour de vie chez un grand premature. Cinq abces cerebraux sont apparus au 6e jour d’une antibiotherapie adaptee (cefotaxime et aminoside) motivant l’association de cefepime et de ciprofloxacine pendant 4 semaines pour la cephalosporine et jusqu’a disparition des images neuroradiologiques pour la fluoroquinolone. L’evolution neurologique etait normale a l’âge de 13 mois. Les indications et la tolerance de la ciprofloxacine en periode neonatale sont discutees.

We studied the clinical isolates Enterococcus faecium NEF1, resistant to high levels of vancomycin (MIC, 512 μg/ml) and teicoplanin (MIC, 64 μg/ml); Enterococcus faecium BM4653 and BM4656 and Enterococcus avium BM4655, resistant to moderate levels of vancomycin (MIC, 32 μg/ml) and to low levels of teicoplanin (MIC, 4 μg/ml); and Enterococcus faecalis BM4654, moderately resistant to vancomycin (MIC, 16 μg/ml) but susceptible to teicoplanin (MIC, 0.5 μg/ml). The strains were distinct, were constitutively resistant via the synthesis of peptidoglycan precursors ending in d -alanyl- d -lactate, and harbored a chromosomal vanD gene cluster that was not transferable. New mutations were found in conserved domains of VanS D : at T 170 I near the phosphorylation site in NEF1, at V 67 A at the membrane surface in BM4653, at G 340 S in the G2 ATP-binding domain in BM4655, in the F domain in BM4656 (a 6-bp insertion), and in the G1 and G2 domains of BM4654 (three mutations). The mutations resulted in constitutivity, presumably through the loss of the phosphatase activity of the sensor. The chromosomal Ddl d -Ala: d -Ala ligase had an IS 19 copy in NEF1, a mutation in the serine (S 185 F) or near the arginine (T 289 P) involved in d -Ala1 binding in BM4653 or BM4655, respectively, and a mutation next to the lysine (P 180 S) involved in d -Ala2 binding in BM4654, leading to the production of an impaired enzyme. In BM4653 vanY D , a new insertion sequence, IS Efa9 , belonging to the IS 3 family, resulted in the absence of d , d -carboxypeptidase activity. Strain BM4656 had a functional d -Ala: d -Ala ligase, associated with high levels of both VanX D and VanY D activities, and is the first example of a VanD-type strain with a functional Ddl enzyme. Study of these five clinical isolates, displaying various assortments of mutations, confirms that all VanD-type strains isolated so far have undergone mutations in the vanS D or vanR D gene, leading to constitutive resistance, but that the Ddl host ligase is not always impaired. Based on sequence differences, the vanD gene clusters could be assigned to two subtypes: vanD-1 and vanD-4 .

Ascochyta blight, caused by the necrotrophic ascomycete Didymella pinodes , is responsible for severe losses in winter and spring pea crops. Despite different climatic conditions, epidemics on winter and spring crops are due to a single population of D. pinodes , suggesting gene flow either between the two crops or from reservoir sources during the cropping season. This should lead to similar pathogenicity characteristics in isolates sampled from the two crops. However, these hypotheses have never been formally tested. We therefore sampled a total of 520 D. pinodes strains throughout a growing season from winter and spring pea plots (WP and SP, respectively) and from winter and spring trap plants (TWP and TSP). Amplified fragment length polymorphism (AFLP) markers revealed high genetic diversity within subpopulations, whereas pathogenicity tests showed that mean aggressiveness increases over the course of an epidemic. These results support the idea that alloinoculum contributes to the carryover of epidemics between winter and spring crops and that the most aggressive isolates are selected as an epidemic progresses. IMPORTANCE Ascochyta blight, caused by Didymella pinodes , is responsible for severe losses in pea crops. While previous studies have shown that ascochyta blight epidemics on winter and spring crops are due to a single population of D. pinodes , suggesting that isolates from the two crops present similar pathogenicity characteristics, that hypothesis have never been tested. Genetic analysis of subpopulations sampled throughout a growing season from winter and spring pea plots revealed high genetic diversity within subpopulations, whereas pathogenicity tests showed that mean aggressiveness increases over the course of an epidemic.

We aimed to gain insight into the alkane degradation potential of microbial communities from chronically polluted sediments of a subantarctic coastal environment using a combination of metagenomic approaches. A total of 6178 sequences annotated as alkane-1-monooxygenases (EC 1.14.15.3) were retrieved from a shotgun metagenomic dataset that included two sites analyzed in triplicate. The majority of the sequences binned with AlkB described in Bacteroidetes (32 ± 13 %) or Proteobacteria (29 ± 7 %), although a large proportion remained unclassified at the phylum level. Operational taxonomic unit (OTU)-based analyses showed small differences in AlkB distribution among samples that could be correlated with alkane concentrations, as well as with site-specific variations in pH and salinity. A number of low-abundance OTUs, mostly affiliated with Actinobacterial sequences, were found to be only present in the most contaminated samples. On the other hand, the molecular screening of a large-insert metagenomic library of intertidal sediments from one of the sampling sites identified two genomic fragments containing novel alkB gene sequences, as well as various contiguous genes related to lipid metabolism. Both genomic fragments were affiliated with the phylum Planctomycetes, and one could be further assigned to the genus Rhodopirellula due to the presence of a partial sequence of the 23S ribosomal RNA (rRNA) gene. This work highlights the diversity of bacterial groups contributing to the alkane degradation potential and reveals patterns of functional diversity in relation with environmental stressors in a chronically polluted, high-latitude coastal environment. In addition, alkane biodegradation genes are described for the first time in members of Planctomycetes. Fil: Guibert, Lilian Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina Fil: Loviso, Claudia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina Fil: Borglin, Sharon. Lawrence Berkeley National Laboratory; Estados Unidos Fil: Jansson, Janet K.. Pacific Northwest National Laboratory; Estados Unidos Fil: Dionisi, Hebe Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina Fil: Lozada, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina

Carrot cavity spot (CCS) is characterised by the appearance of small sunken elliptical lesions on the tap root. It is caused by a complex of Pythium species, but the species diversity and interactions within the complex have never been studied for modelling CCS epidemics. The diversity of a pathogenic Pythium community was assessed during 3 consecutive years in a field experiment after an initial artificial soil infestation with P. violae . 1241 lesions were examined, yielding 728 Pythium isolates. Conventional microbiological methods and restriction polymorphism of the internal transcribed spacer regions of the rDNA of 209 representative Pythium isolates allowed us to identify 655 isolates as belonging to six Pythium species, including P. violae and five indigenous species ( P. sulcatum , P. intermedium , P. sylvaticum / irregulare , P. coloratum , and P. ultimum ). Biological traits, such as pathogenicity, optimum temperature for mycelial growth and saprophytic survival of the inoculum, explained the fluctuations in the composition of the complex over 17 successive samplings during the 3-year period, most notably the prevalence of first P. violae and then P. sulcatum . P. violae and P. sulcatum were occasionally isolated in mixture from single lesions (10.4% and 9.6%, respectively). Other species were more frequently isolated in mixture: 30.8% for P. intermedium , 33.8% for P. sylvaticum/irregulare , 42.9% for P. ultimum , and 66.7% for P. coloratum . A contingency analysis allowed us to define ‘major’ and ‘minor’ species on both pathological and ecological criteria (frequency of occurrence in the complex, pathogenicity and ability to induce lesions by themselves), and demonstrated that infection by one ‘major’ pathogen species ( P. violae or P. sulcatum ) is not positively correlated with the presence of a second Pythium species. The ratio between ‘observed’ and ‘expected’ mixed infection frequency under the assumption of independent infection ( mir ) was less than 1 for P. violae , P. sulcatum , P. intermedium , and P. sylvaticum/irregulare ( P Pythium species, there was a negative linear relationship between mir and pathogenicity ( R 2 = 0.638): the less a Pythium species was pathogenic on carrot, the more often it was isolated from a CCS lesion in mixture with at least one other species. The non-significance of interactions between species during the infection phase suggests that CCS epidemics can be analysed as if they were caused by a single Pythium species.

Aims: To investigate the potential to degrade polycyclic aromatic hydrocarbons (PAHs) of yet-to-be-cultured bacterial populations from chronically polluted intertidal sediments. Methods and Results: A gene variant encoding the alpha subunit of the catalytic component of an aromatic-ring-hydroxylating oxygenase (RHO) was abundant in intertidal sediments from chronically polluted subantarctic and temperate coastal environments, and its abundance increased after PAH amendment. Conversely, this marker gene was not detected in sediments from a nonimpacted site, even after a short-term PAH exposure. A metagenomic fragment carrying this gene variant was identified in a fosmid library of subantarctic sediments. This fragment contained five pairs of alpha and beta subunit genes and a lone alpha subunit gene of oxygenases, classified as belonging to three different RHO functional classes. In silico structural analysis suggested that two of these oxygenases contain large substrate-binding pockets, capable of accepting high molecular weight PAHs. Conclusions: The identified uncultured micro-organism presents the potential to degrade aromatic hydrocarbons with various chemical structures, and could represent an important member of the PAH-degrading community in these polluted coastal environments. Significance and Impact of the Study: This work provides valuable information for the design of environmental molecular diagnostic tools and for the biotechnological application of RHO enzymes. Fil: Loviso, Claudia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina Fil: Lozada, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Guibert, Lilian Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina Fil: Musumeci, Matias Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Sarango Cardenas, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Kuin, Ruud V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Marcos, Magalí Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Dionisi, Hebe Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina

Headache is common in systemic lupus erythematosus with reported prevalence as high as 70%. The aims of this study were: to estimate the prevalence and types of headache in a sample of patients with systemic lupus erythematosus comparing it with rheumatoid arthritis, to determine clinical and serological associations. Eighty-one systemic lupus erythematosus and 29 rheumatoid arthritis consecutive patients seen in our outpatient clinic were interviewed. Headache was evaluated using the diagnostic criteria proposed by the International Headache Society. Additional evaluations were carried out in the 81 systemic lupus erythematosus patients including depression, disease activity, lupus damage, function disability, quality of life, and severity degree using a validated scales. We analysed the following autoantibodies: anti-double stranded DNA, anti-nucleosomes, anti-histones, anti-ribosomal P, anti-cardiolipin antibodies, anti-β2-glycoprotein-I (GPI), and antinuclear antibodies. Forty-one per cent of systemic lupus erythematosus and 17% of rheumatoid arthritis patients suffered from headache ( P = 0.02). No significant difference for any primary headache type between the two groups was found. Frequency of headache types in systemic lupus erythematosus patients was: migraine 24%, tensional-type headache 11%, and mixed headache 5%. In systemic lupus erythematosus patients the risk factors associated with headaches were Raynaud's phenomenon (OR 3.6; 95% CI 1.3-9.5; P = 0.009) and β2GPI antibody positivity (OR 4.5; 95% CI 1.2-16.2; p = 0.016). We conclude that headache is more common in systemic lupus erythematosus than in rheumatoid arthritis patients and was independently associated with Raynaud's phenomenon and β2GP-I antibodies.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Bien qu'elle soit relativement rare, estimee selon les definitions a 2 a 5 pour 1 000 naissances, l'infection maternofœtale constitue l'une des preoccupations permanentes du pediatre de maternite, en raison de sa gravite potentielle et des difficultes de diagnostic. Une fois le diagnostic evoque et l'indication d'antibiotherapie posee, reste la question du choix du ou des antibiotiques de premiere intention, avant identification du germe et de sa sensibilite.

Pseudomonas aeruginosa, together with enterobacterial species, i.e. Enterobacter spp., Serratia marcescens, Citrobacter freundii, Morganella morganii and Yersinia enterocolitica possess a naturally-occurring cephalosporinase This enzyme when expressed at a low level confers resistance to aminopenicillins. first-generation cephalosporins, such as cephalothin, and cephamycins such as cefoxitin. This AmpC β-lactamase (commonly called cephalosporinase) is not inhibited by the currently available β-lactam inhibitors, clavulanic acid, sulbactam and tazobactam, therefore additionally conferring resistance to antibiotic combinations such as co-amoxiclav or ampicillin/sulbactam. P. aeruginosa is, however, naturally susceptible to ureido- and carboxypenicillins, aztreonam and third-generation cephalosporins such as ceftazidime. Its intermediate susceptibility towards some other third-generation cephalosporins (cefotaxime or ceftriaxone) results either from its intrinsic low outer-membrane permeability (one-hundredth of that of Escherichia coli) 3 or from antibiotic efflux.

Contagious agalactia caused by Mycoplasma agalactiae is a major cause of mastitis in ewes and goats. To explore the first stages of infection, an experimental infection in lambs has been developed, using the strain P89 of M. agalactiae . Lambs were inoculated by the conjunctival route with various doses of viable bacteria. Following necropsy at regular intervals, enumeration of viable bacteria was performed on various organs including the lymph nodes (LNs) draining the conjunctiva. A rapid colonization of LNs from Day 7 (Group 10 9 colony-forming units [CFU]) or from Day 14 (Group 10 7 CFU) post-inoculation (p.i.) was observed and was associated with a transient infection of the spleen suggesting a bacteriemic phase. In a second experiment, lambs were inoculated with the 10 7 dose which had induced a regular infection on Day 14 p.i. in the first experiment. The lambs were necropsied on Days 14 or 56 p.i. The bacteriological examinations of the group necropsied on Day 14 p.i. confirmed the previous results. On Day 56 p.i., the infection decreased but all head LNs remained infected and M. agalactiae was still present at the inoculation site in one lamb, suggesting that M. agalactiae can persist for a long time in its host. This experimental model, using lambs inoculated by the conjunctival route and slaughtered 14 days after inoculation, was simple and easily reproducible, in comparison with a model using lactating ewes. This model can be used to compare virulence of field strains and to test protection following immunization of lambs with attenuated strains of M. agalactiae or with antigens.

Resume Malgre la frequence de la colonisation vaginale a levures, les infections systemiques severes tant maternelles que fœtales restent rares. Nous rapportons quatre cas de candidose generalisee congenitale chez de grands prematures. Leur semiologie caracteristique a permis d'en faire precocement le diagnostic. Observations. — Un diagnostic d'infection maternofœtale (IMF) a Candida albicans a ete porte chez quatre grands prematures. Dans trois cas, la grossesse s'etait developpee malgre la presence d'un sterilet. Un examen macroscopique attentif du cordon et des membranes amniotiques a permis d'orienter d'emblee la prise en charge a trois reprises. Une alveolite infectieuse severe est constamment retrouvee dans cette serie. Une hyperleucocytose superieure a 50 000 GB/mm3 avec myelemie et une proteine C reactive (CRP) serique normale ou peu elevee sont typiques du tableau biologique. L'infection est controlee indifferemment par l'administration intraveineuse d'amphotericine B ou de fluconazole; un cas d'intolerance a l'amphotericine B nous a cependant contraints a changer d'antifongique en cours de trailement. L'evolution s'est compliquee par deux fois d'une leucomalacie periventriculaire cavitaire etendue. Conclusion. — Un tableau evocaleur d'IMF a Candida chez le grand premature peut etre degage de ces quatre observations: grossesse sur sterilet, chorioamniotite et funiculite caracteristiques, hyperleucocylose superiure a 50 000 GB/mm3, alveolite infectieuse severe. Nous proposons le fluconazole de premiere intention comme alternative interessante a l'amphotericine B.

Resume Les mycoplasmes uro-genitaux (MUG), Ureaplasma urealyticum et Mycoplasma hominis sont impliques comme agents pathogenes dans les urethrites non gonococciques, les chorio-amniotites, les salpingites et les septicemies du post-partum. Dans les pathologies de la reproduction, le role de ces germes est encore mal defini. En pathologie neonatale, le role des MUG a ete discute dans les infections pulmonaires et les meningites. Pendant une annee, une etude prospective a ete menee incluant 80 nouveau-nes prematures afin de determiner la frequence, l'importance et l'evolution de la colonisation par les MUG pendant la duree d'intubation ainsi que les consequences eventuelles sur le developpement d'une dysplasie broncho-pulmonaire (DBP). La recherche des MUG a ete effectuee systematiquement a la naissance dans le liquide gastrique, la trachee et le sang puis une fois par semaine dans l'aspiration tracheale des enfants restes intubes. Les frequences de colonisation etaient a la naissance de 16,2 % pour U. urealyticum et de 2,5 % pour M. hominis . Le suivi de la colonisation tracheale par les MUG montrait que celle-ci n'etait pas un facteur etiologique isole d'une DBP. Par contre chez les enfants ayant developpe une DBP, la colonisation par les MUG entrainait une prolongation de la duree d'intubation. Cette colonisation jouerait donc un role dans la persistance ou le retard de la guerison de la DBP.

Resume La connaissance de la bacteriologie des peritonites est fondamentale dans le choix du traitement antibiotique. Cependant, la diversite des peritonites a conduit a proposer differents systemes de classification parmi lesquels le caractere communautaire ou nosocomial. Cette distinction est primordiale en raison des differences microbiologiques entre les peritonites communautaires ou nosocomiales. Les divergences portent autant sur les indications et l'interpretation des resultats des prelevements intra-peritoneaux que sur les micro-organismes en cause et leur sensibilite aux antibiotiques. Au cours des peritonites communautaires, l'antibiotherapie est necessairement empirique, fondee sur les modeles experimentaux et sur les etudes epidemiologiques, l'interet des prelevements locaux est limite. A l'inverse au cours des peritonites nosocomiales les modeles experimentaux classiques semblent peu applicables, les etudes epidemiologiques sont peu nombreuses, la pathogenicite des germes est inconstamment demontree, aussi une bonne analyse des resultats bacteriologiques intra-peritoneaux integrant les donnees de l'ecologie microbienne de l'unite constitue la base de la reflexion therapeutique.

The aim of the present study was to determine whether, in patients with depression who had responded favourably to the selective serotonin reuptake inhibitor citalopram, there was a therapeutic benefit in continuation treatment. Three hundred and ninety-one depressive patients were included in an open short-term citalopram treatment period. Only patients who responded to treatment at 8 weeks (total score of 12 or less on the MADRS scale) were randomized to the 24 week double-blind phase. Seventy-four patients were treated with placebo and 152 with citalopram at the same constant dose to which the patient had responded in the first phase. Relapse was defined as a total score of 25 or more on the MADRS scale. Twenty-one patients (13.8%) continuing to receive citalopram relapsed compared with 18 patients (24.3%) receiving placebo. The log rank test for survival data used to test the quality of relapse hazards between the placebo group and the citalopram group showed that patients treated with citalopram had a significantly lower relapse rate (p = 0.04). The results of this study are in general agreement with those of other studies on antidepressants, and support the hypothesis that full dose continuation is more effective than placebo in preventing relapse of depression.

The French Ministry of Health and its regional agencies decided on December 27th, 2010 to develop the ambulatory surgery in the purpose to eliminate 48,000 beds of surgery in France. This evolution, which results from Anglo-Saxon countries, is inevitable in front of the financial deficit of our health insurance. Like the Canadian plastic surgeons, who were forced to it for 7 years, we wanted to study the feasibility of an ambulatory care of the reduction mammaplasties in a hospitalo-university department.Between January and June, 2012, 25 patients, of less than 65 years old, were operated for a reduction mammaplasty scheduled in ambulatory. None presented particular anesthetic risk. All lived unless 1h of the hospital, went out accompanied, were revised the day after the intervention, then in a usual way. Our criterias of evaluation were the following ones: global satisfaction of the care in ambulatory, weight of glandular resection, postoperative complications, rate of readmission.The average age of the patients was 32 years (19-56 years). The average weight of resection was 400g by breast (140-1000g). Twenty patients went out on evening (80%). Among them, 19 (95%) expressed their satisfaction and would accept again this intervention in ambulatory. No major complication arose in this series. Five other patients saw their release repelled by the anaesthetists for the following motives: score of Aldrete lower than 9, pain not relieved by the analgesic (I or II), nausea and uncontrollable vomitings.This first clinical study realized in France, confirms that when certain conditions are filled, the reduction mammaplasty can be realized in ambulatory with complete safety. The rate of satisfaction shows a very strong support of the patients for the ambulatory care.

Scanning LIDARs are widely used as 3D sensors for navigation due to their ability to provide 3D information of terrains and obstacles with a high degree of precision. The optics of conventional scanning LIDARs are generally monostatic, i.e. launch beam and return beam share the same optical path in scanning optics. As a consequence, LIDARs with monostatic optics suffer poor performance at short range (

Although sediments are the natural hydrocarbon sink in the marine environment, the ecology of hydrocarbon-degrading bacteria in sediments is poorly understood, especially in cold regions. We studied the diversity of alkane-degrading bacterial populations and their response to oil exposure in sediments of a chronically polluted Subantarctic coastal environment, by analyzing alkane monooxygenase (alkB) gene libraries. Sequences from the sediment clone libraries were affiliated with genes described in Proteobacteria and Actinobacteria, with 67 % amino acid identity in average to sequences from isolated microorganisms. The majority of the sequences were most closely related to uncultured microorganisms from cold marine sediments or soils from high latitude regions, highlighting the role of temperature in the structuring of this bacterial guild. The distribution of alkB sequences among samples of different sites and years, and selection after experimental oil exposure allowed us to identify ecologically relevant alkB genes in Subantarctic sediments, which could be used as biomarkers for alkane biodegradation in this environment. 16 S rRNA amplicon pyrosequencing indicated the abundance of several genera for which no alkB genes have yet been described (Oleispira, Thalassospira) or that have not been previously associated with oil biodegradation (Spongiibacter—formerly Melitea—, Maribius, Robiginitomaculum, Bizionia and Gillisia). These genera constitute candidates for future work involving identification of hydrocarbon biodegradation pathway genes.

Objective To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline. Methods Clinical evaluation, ethnicity, socioeconomic status (SES), 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (

Plant diseases are caused by pathogen populations continuously subjected to evolutionary forces (genetic flow, selection, and recombination). Ascochyta blight, caused by Mycosphaerella pinodes , is one of the most damaging necrotrophic pathogens of field peas worldwide. In France, both winter and spring peas are cultivated. Although these crops overlap by about 4 months (March to June), primary Ascochyta blight infections are not synchronous on the two crops. This suggests that the disease could be due to two different M. pinodes populations, specialized on either winter or spring pea. To test this hypothesis, 144 pathogen isolates were collected in the field during the winter and spring growing seasons in Rennes (western France), and all the isolates were genotyped using amplified fragment length polymorphism (AFLP) markers. Furthermore, the pathogenicities of 33 isolates randomly chosen within the collection were tested on four pea genotypes (2 winter and 2 spring types) grown under three climatic regimes, simulating winter, late winter, and spring conditions. M. pinodes isolates from winter and spring peas were genetically polymorphic but not differentiated according to the type of cultivars. Isolates from winter pea were more pathogenic than isolates from spring pea on hosts raised under winter conditions, while isolates from spring pea were more pathogenic than those from winter pea on plants raised under spring conditions. These results show that disease developed on winter and spring peas was initiated by a single population of M. pinodes whose pathogenicity is a plastic trait modulated by the physiological status of the host plant.

Resume Le sepsis est une cause importante de morbidite au sein de la population obstetricale, la grossesse etant en elle-meme un facteur de risque de survenue de choc septique. Le potentiel evolutif de ces pathologies est ainsi redoutable. Le sepsis grave conduisant a l'hospitalisation des patientes et a leur admission en reanimation reste cependant relativement rare. Les modifications physiologiques de la grossesse (modifications cardiovasculaire et respiratoire, modifications des defenses immunitaires) peuvent theoriquement influencer l'evolutivite et la gravite du choc septique. Cette complication est elle-meme impliquee dans la genese d'autres defaillances : syndrome de detresse respiratoire aigue, defaillance multiviscerale et coagulopathie de consommation. Le taux de mortalite des chocs septiques en obstetrique est estime entre 20 % et 50 %. Il est de plus admis qu'environ 70 % des deces maternels pour sepsis sont evitables. Les pathologies infectieuses le plus frequemment en cause sont les pyelonephrites, les infections du liquide amniotique avec chorioamniotites et endometrites et les pneumopathies bacteriennes ou virales. Ces elements justifient une prise en charge precoce et agressive par une equipe associant obstetriciens et anesthesiste-reanimateurs de ces malades, afin d'eviter une evolution encore trop souvent dramatique.

With the ever growing interest in wavelength division multiplexing transmission systems, the need for an optical amplifier with a large bandwidth is more and more necessary. Unlike the standard erbium-doped silica fiber amplifiers, the fluoride-based fiber amplifiers display more uniform gain spectra. The benefit expected from fluoride amplifiers with multiwavelength signals has been experimentally assessed through comparisons in single- and cascaded-amplifiers configurations. Four db gain flatness was achieved with four wavelength-multiplexed signals extending over 23 nm after three fluoride amplifiers while 15 dB gain unbalance was observed after three silica amplifiers. This result shows that fluoride amplifiers may be of the utmost relevance for multiwavelength transport systems. >

Interest behavior of the flattened dynamic gain of an erbium-doped fluorozirconate fiber amplifier is demonstrated in a lightwave CATV system including a 50-channel subcarrier multiplexer. Using two analog distributed-feedback (DFB) laser diodes, one with a relatively high chirp and the other with a very low chirp, a comparison between amplifiers made of erbium-doped silica and fluoride fiber demonstrates the significant influence of the laser FM response when the spectral dynamic gain of the amplifier is not constant. >

A neonatal infection with Enterobacter cloacae was diagnosed at day 21 in a premature infant. Five cerebral abscesses were discovered 6 days while a treatment with cefotaxim and amikacin was administered. We switched for axepim during 4 weeks and ciprofloxacin until complete regression of cerebral abscesses. At 13 months of age, the infant neurodevelopmental outcome was normal. Ciprofloxacin indications and tolerance during neonatal period are discussed.

We report three cases of severe community-acquired Legionella pneumophila pneumonia with acute pancreatitis. Pancreas involvement is unusual. The clinical presentations consisted of painless pancreatitis with only elevation of serum pancreatic enzymes (case 1), tender abdomen with edematous pancreas on computed tomography scan (case 2) and necrosis (case 3). We discuss the possible mechanisms of L. pneumophila associated acute pancreatitis for which the pathophysiology is still undetermined: infection, toxin release or cytokine secretion.

Rapid assays for Escherichia coli have been developed by using the fluorogenic compound 4-methylumbelliferyl β-d-glucuronide (MUG), which is hydrolysed by glucuronidase to yield a fluorescent product that is visible under long-wave u.v. light (Feng and Hartman, 1982; Alvarez, 1984; Koburger and Miller, 1985; Rippey et al., 1987). MUG was incorporated into a Al-broth (Andrews and Presnell, 1972) at a final concentration of 100 mg/l. To each well of a sterile 96-well microtitration plate, 100 μl of Al-MUG medium was added. The plate was then air dried, covered with a sterile tape and stored at 4°C. To enumerate E. coli using the miniaturized multi-tube MPN procedure, 200 μl of diluted or undiluted water was added to each well of a microtiter plate. The number of rows inoculated with each dilution depended on the presumptive contamination level of the samples (Table 1). The plate was incubated for 18 h at 44.5°C and observed in the dark for fluorescence by using a long wave (366 nm) u.v. light source. Raw surface water, wastewater effluents, human and animal faeces were collected for the specificity studies. Fluorescent positive wells were then confirmed for the presence of E. coli by transfer to Schubert broth and incubation at 44.5°C for 24 h. Strains cultivable at 44.5°C, with gas and indole production were considered as E. coli. In addition, gas or indole negative strains were identified using API 20E strips. The Schubert broth test for E. coli confirmed that approx. 88.3% of the fluorescent wells contained E. coli. An 11.7% apparently false-positive rate was also observed. But most interestingly 21 fluorescent wells (5%) that were gas (−) in the Schubert test were confirmed as anaerogenic strains of E. coli with API identification strips. Also 8 fluorescent wells (2%) that were indole (−) in the Schubert test were confirmed as indole (−) strains of E. coli by API strips. So only a 4.8% false-positive rate was observed (Table 3). A study with 5 collaborating laboratories (Nice, Montpellier, Bordeaux, Le Havre and Lille) was conducted in France from June to September 1988 to compare the microtiter plate MPN test with the standard methods: • -3-tube MPN procedure (NPP a 3 tubes), • -membrane filtration (FM), • -Pour Plate Count (IG). Media, time and temperature of incubation, positivity and volumes inoculated are reported in Table 2. Subsurface marine waters were collected aseptically by hand. Testing for E. coli was made before 8 h after collection. Marine waters were collected from the Mediterranean Sea, Atlantic Ocean, English Channel and North Sea. The results indicate that the microtiter plate with MUG had a better specificity than the current methods tested (Table 4). Indeed, 87.3% confirmative rate in the Schubert broth was observed with the fluorogenic assay when 31.7 and 4.10% false-positive rates were observed with FM and IG methods respectively. According to our results, the microtiter plate MUG has been found to be a very consistent and accurate method for the detection and enumeration of E. coli. The performance is equal to 3-tube MPN and FM and better than the IG (Table 5). In conclusion, the microtiter plate method seems to be applicable to routine E. coli enumeration, by incorporating MUG into a selective medium and air drying the medium in a microtitration plate. The ability to detect E. coli is thus improved, and the amount of time and labour required for each analysis is reduced. More precise MPN estimates of E. coli numbers are yielded, and the inoculation and reading of the microtiter plates are easely amenable to automation. By eliminating the battery of biochemical tests, and laborious manipulations required for E. coli identification, and yet providing simplicity, sensitivity and specificity, this method might be an alternative to current estimation of the faecal pollution by the so-called “thermotolerant coliforms” for ill-defined “faecal coliforms”.

To detect E. coli, 4-methylumbelliferyl α-D-glucuronide (MUG) was incorporated into a modified Al-broth. To detect enterococci, 4-methylumbelliferyl α-D-glucoside (MUD) was incorporated into a selective medium. To each well of a sterile 96-well microtitration plate, 100 µl of media was added, air dried, covered with sterile tape and stored at 4°C. To enumerate the indicator bacteria using this method, 200 µ1 of diluted or undiluted water was added to wells with MUG and MUD media. The plates were incubated for 36-40 hours at 44°C and observed in the dark for fluorescence by UV light (366nm). Fifty subsurface marine waters from four areas were examined. The recovery rate of the fluorogenic assays is equal or superior to 3-tubes MPN and membrane filtration. The microtitration plate with MUG is more specific for E. coli than the membrane filtration. A 87.4 % confirmation rate was observed with the fluorogenic assay compared to a 31.7 % false-positive rate with membranes. For the enterococci, the analysis of 23 English Channel and North Sea samples indicated that the fluorogenic assay and the standard methods had the same specificity (

Two infants, aged 8.5 and 11 months, were admitted for meningitis caused by Streptococcus pneumoniae. Failure of cefotaxime led to the identification of highly penicillin-G-resistant strains. Minimum inhibitory concentrations (MICs) for penicillin were2 μg/ml, and cefotaxime MICs were 2 μg/ml. Both patients rapidly responded to a combination of iv imipenem and rifampicin. It is now mandatory to test in-vitro susceptibilities of Streptococcus pneumoniae to penicillin G and other beta-lactam agents when meningitis is diagnosed in infants. Antibiotics, meningitis, Streptococcus pneumoniae

We investigated the genetic diversity of 179 Staphylococcus aureus isolates recovered from various sites in 10 farms producing cheeses manufactured with raw ewe's milk. Isolates were collected from handcrafted cheeses, bulk tank milk, milk from half-udders, skin abscesses on the udder if present, hands and anterior nares of farmers, and air of the milking area. The isolates were typed using pulsed-field gel electrophoresis (PFGE) of DNA SmaI digests and compared to other isolates of S. aureus isolated in different hosts or in different locations. The results showed that nine farms were contaminated by S. aureus isolates with identical banding patterns (named OV) or by genetically related isolates (named OV'). These dominant banding patterns were found in a variable proportion of the samples from each farm (range: 11-100%). Most of the strains isolated from nasal carriage or strains isolated from other regions or from other animal species had different PFGE patterns to OV or OV', except for three strains. These results show that a single clone of S. aureus is widely distributed both in infected mammary glands and in cheese produced from raw milk. This study confirms that infected mammary glands are the main source of the contamination of dairy products in sheep.

A new type of optical fibre amplifier, a ‘hybrid amplifier’, especially developed for multiwavelength long distance transmission systems in the 1.55 µm window is presented. A 38 dB small signal gain, an +18 dBm saturation output power, a very flat gain spectrum and a very high signal-to-noise-ratio are obtained.