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Objective The aim of this study was to determine the in vitro activity of six new antimicrobial agents against glycopeptide-resistant enterococci (GRE) strains from France. Methods Sixty epidemiologically unrelated clinical isolates of Enterococcus faecium ( vanA or vanB ), received at the National Reference Centre for Enterococci (CNR-Enc) between 2006 and 2008, were studied. The MICs of the following antibiotics were determined by broth microdilution according to Antibiogram Committee of the French Society for Microbiology (CA-SFM) guidelines: quinupristin-dalfopristin (Q-D), linezolid (LZD), daptomycin (DPT), tigecycline (TGC), ceftobiprole (CFT), and telavancin (TLV). Strains were classified using clinical breakpoints recommended by the CA-SFM (Q-D, LZD, TGC), or the Clinical and Laboratory Standards Institute (DPT). Results All strains were susceptible to LZD and DPT (MIC 90 , 4 and 2 μg/ml, respectively) and only a single strain presented intermediate susceptibility to tigecycline (MIC 90 , 0.25 μg/ml). Thirty percent of strains were resistant to Q-D (MIC 90 , 4 μg/ml), and CFT was constantly inactive (MIC 90 , 64 μg/ml). Finally, TLV showed low-level MICs (MIC 90 , 0.5 μg/ml) against vanB -positive isolates but not against vanA -positive isolates (MIC 90 , 8 μg/ml). Conclusion Although several antibiotics are still active against GRE, it is essential to maintain an active antimicrobial resistance surveillance for these microorganisms considered as a model of multidrug resistance with a potential to transfer resistance to other bacterial species (e.g. Staphylococcus aureus ).

This study investigated the infection process of Mycosphaerella graminicola and enzyme activities related to reactive oxygen species (ROS) or oxylipin biosynthesis in four French wheat cultivars with variable resistance to M. graminicola infection. At field level, cultivars Caphorn, Maxyl and Gen11 were susceptible, whereas Capnor showed high levels of quantitative resistance. Moreover, Capnor and Gen11 were tolerant, i.e., their yield was less affected by infection compared to non-tolerant Maxyl and Caphorn. These four cultivars were inoculated under laboratory conditions with the M. graminicola IPO323 reference strain. Cytological and biochemical responses were studied on collected first plantlet leaves and several features discriminated between cultivars. However, resistance and tolerance had no impact on the fungal infection process. Levels of lipoxygenase (LOX), peroxidase (PO) and glutathione-S-transferase (GST) activities were also compared with regard to cultivar resistance or tolerance to M. graminicola. LOX, PO and GST activities did not discriminate resistance and tolerance profiles, although a low level of PO in inoculated and non-inoculated plants could be associated with tolerance. In addition, cell necrosis correlated positively with LOX in non-tolerant cultivars, while mycelia surrounding stomata were positively correlated with PO in the resistant cultivar. GST activity presented correlations between cytological and biochemical parameters only for susceptible cultivars. Stomatal and direct penetration were positively correlated with GST activity in the susceptible non-tolerant cultivars, while these correlations were negative in the tolerant cultivar. When combining cytological and biochemical observations with resistance and tolerance profiles, for each cultivar and at each time point, cultivars could be classified in tight accordance with their previous field characterisation. Moreover, tolerance allowed us to distinguish susceptible cultivars when both biochemical and cytological parameters were considered together.

Resume Introduction Des epidemies d’enterocoques resistants a la vancomycine ont ete decrites en France depuis trois ans. Nous rapportons un cas d’emergence d’une souche d’enterocoque dependante de la vancomycine a la suite d’un traitement par glycopeptide. Patients et methodes Une souche d’Enterococcus faecium dependante de la vancomycine pour sa croissance a ete isolee a partir des selles d’une patiente transplantee hepatique porteuse d’enterocoque resistant a la vancomycine avant la greffe, puis traitee par vancomycine pour une infection a Staphylococcus aureus resistant a la meticilline. La souche resistante et la souche dependante ont ete typees par electrophorese en champ pulse. Le gene ddl codant pour la d -Ala : d -Ala ligase a ete amplifie par PCR et sequence. Resultats La souche dependante a ete isolee initialement sur un milieu selectif contenant de la vancomycine et n’a pu etre obtenue en subculture qu’en presence de cet antibiotique. La souche resistante et la souche dependante possedaient le gene vanA et presentaient le meme profil de restriction par electrophorese en champ pulse. La dependance a la vancomycine etait associee a la deletion d’une paire de bases dans la sequence du gene ddl provoquant un decalage du cadre de lecture et l’apparition d’un codon stop premature. Conclusion Les prelevements cliniques des patients porteurs d’enterocoque resistant a la vancomycine et traites par glycopeptide doivent etre cultives sur des milieux contenant de la vancomycine afin de detecter l’emergence de souches dependantes.

Our work aimed at a global investigation of the lipid metabolism during the induction of resistance in wheat (Triticum aestivum) against powdery mildew (Blumeria graminis f.sp. tritici). More specifically, the effect of salicylic acid, known as playing a key role in the activation of defence reactions against pathogens in plants, has been investigated. After salicylic acid infiltration, accumulation of phosphatidic acid was observed that could be due to the phospholipase C pathway since an up-regulation of a phospholipase C-encoding gene expression as well as an accumulation of diacylglycerol were observed. The phosphatidic acid accumulation could also result from the phospholipase D pathway since a reduction of phosphatidylethanolamine content occurred. The response to salicylic acid at the octadecanoid pathway level was also investigated: both a lipoxygenase-encoding gene expression and lipoxygenase enzymatic activity were induced by salicylic acid simultaneously with a decrease of the linolenic acid content. Finally, a lipid transfer protein-encoding gene expression was also up-regulated upon salicylic acid infiltration. These observations indicate that lipid metabolism could be considered as a marker of elicitation in wheat.

Three families of lipopeptides (LPs), surfactin, iturin (including mycosutilin) and fengycin, produced by the rhizabacterium Bacillus subtilis have received considerable attention for their antimicrobial, cytotoxic, antitumor, immunosuppressant and surfactant properties. Among them, iturins and fengycins generally display a strong in vitro antifungal activity. In addition, surfactins are powerful bio surfactants, and although they don't show any direct fungitoxicity, they exhibit some synergistic effect with the antifungal activity of iturins. The aim of our work is to characterize mycosubtilin, surfactin and fengycin, for their ability to protect wheat against two pathogens, Blumeria graminis f.sp. tritici (Bgt), an obligate parasitic fungus responsible for powdery mildew and Mycosphaerella graminicola (Mg), an hemibiotrophic fungus causing Septoria leaf blotch, two of the most important diseases of this crop. In a first step, we measured the protection efficacy of a preventive treatment with LPs against powdery mildew on wheat leaves. At least 41% and 44% protection levels were obtained when surfactin and mycosubtilin, respectively, were sprayed on wheat leaves at doses corresponding to 4g.ha(-1) in the field. We also tested in vitro the impact of LPs on germination of spores. No direct antifungal effect of LPs was observed on Bgt conidia germination, irrespective of the tested concentrations. However, fengycin strongly decreased the germination of Mg conidia and also considerably delayed its growth. Mycasubtilin completely inhibited conidial germination and therefore also its growth while surfactin did not remarkably affect either germination or growth of this fungus. In a second step, RT-qPCR was used to investigate elicitor and priming effects of surfactin and mycosubtilin on the expression levels of defence-related genes. In non-infectious conditions, both surfactin and mycosubtilin induced the expression of two peroxidase encoding genes (POX2, POX381), however, the expression of LOX (lipoxygenase), AOS (allene oxide synthase) genes involved in the octadecanoid pathway, as well as of the pathogenesis-related genes PR1 was only induced by mycosubtilin. In infectious conditions, only surfactin induced the expression of these genes in response to pBgt, mycosubtilin did not exhibit any priming effect. Depending on the targeted pathogen and on the type of LP, these molecules could exhibit direct antifungal effect and/or defence induction, through either elicitation or potentialisation.

We dissected 30 facial nerves in fresh cadavers after arterial casting with red latex to provide specific information about the arterial-related anatomy of the trunk of the facial nerve from the stylomastoid foramen to its bifurcation. We found that a wide anatomic variability does exist. The trunk of the facial nerve was in proximity to the stylomastoid artery, which originated from the posterior auricular artery in 70% of the specimens (21/30), from the occipital artery in 20% (6/30), and directly from the external carotid artery in 10% (3/30). The stylomastoid artery passed medially to the trunk of the facial nerve in 63 of the specimens (19/30) and laterally in 37% (11/30). Among these 11 specimens, 8 were large-caliber stylomastoid arteries. During parotid surgery, the main trunk of the facial nerve may be difficult to identify, because a large-caliber stylomastoid artery can mask it. Therefore, it is important to dissect this artery with caution.

In conventional agricultural practices, fungicides are extensively used to control the development of many fungal plant pathogens. However, the reduction of pesticide applications in the field, which is recommended by authorities and approved by public opinion, may lead to a re-emergence of diseases. Alternative strategies have therefore to be developed in order to control fungal infection; one of them is based on plants natural resistance reinforcement caused by elicitors. Our project aims at characterizing mycosubtilin, surfactin and fengycin, three bacterial cyclic non-ribosomal lipopeptides produced by the rhizobacterium Bacillus subtilis, for their ability to induce resistance in wheat against powdery mildew (Blumeria graminis f.sp. tritici). RT-qPCR approach was used to investigate effect of lipopeptides on expression pattern of defence-related genes, such as PR protein-encoding genes or genes involved in plant defence pathways (reactive oxygen species (ROS) metabolism, lipid peroxidation, phenylpropanoid and octadecanoid pathways) in response to fungus and revealed that expression of LOX and PR1 was strongly induced by surfactin at 24h and 18h after inoculation, respectively. Mycosubtilin seemed to be more efficace to induce expression of OXO and Ltp. Surfactin could also induce expression of chitinase encoding genes but neither surfactin nor mycosubtilin could induce the expression of GSTphi and PAL genes in response to the fungus.

This study investigated the infection process of Mycosphaerella graminicola and enzyme activities related to reactive oxygen species (ROS) or oxylipin biosynthesis in four French wheat cultivars with variable resistance to M. graminicola infection. At field level, cultivars Caphorn, Maxyl and Gen11 were susceptible, whereas Capnor showed high levels of quantitative resistance. Moreover, Capnor and Gen11 were tolerant, i.e., their yield was less affected by infection compared to non-tolerant Maxyl and Caphorn. These four cultivars were inoculated under laboratory conditions with the M. graminicola IPO323 reference strain. Cytological and biochemical responses were studied on collected first plantlet leaves and several features discriminated between cultivars. However, resistance and tolerance had no impact on the fungal infection process. Levels of lipoxygenase (LOX), peroxidase (PO) and glutathione-S-transferase (GST) activities were also compared with regard to cultivar resistance or tolerance to M. graminicola. LOX, PO and GST activities did not discriminate resistance and tolerance profiles, although a low level of PO in inoculated and non-inoculated plants could be associated with tolerance. In addition, cell necrosis correlated positively with LOX in non-tolerant cultivars, while mycelia surrounding stomata were positively correlated with PO in the resistant cultivar. GST activity presented correlations between cytological and biochemical parameters only for susceptible cultivars. Stomatal and direct penetration were positively correlated with GST activity in the susceptible non-tolerant cultivars, while these correlations were negative in the tolerant cultivar. When combining cytological and biochemical observations with resistance and tolerance profiles, for each cultivar and at each time point, cultivars could be classified in tight accordance with their previous field characterisation. Moreover, tolerance allowed us to distinguish susceptible cultivars when both biochemical and cytological parameters were considered together.

The aim of this study was to investigate the infection process of M. graminicola and the defence mechanisms related to active oxygen species (AOS) in five French wheat cultivars. These cultivars exhibited various resistant levels to M. graminicola infection: Maxyl, Caphorn and Gen11 are susceptible cultivars, whereas Capnor and Gen23 show high levels of quantitative resistances. In addition, Capnor, Gen23 and Gen11 are tolerant cultivars, i.e., their yield performance was less affected by infection compared to non-tolerant cultivars. Cultivars were inoculated with the IPO323 reference M. graminicola strain. First wheat leaves were collected 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days after inoculation. The cytological and antioxidant response of the cultivars were both studied over the whole time course. Although infection occurred mainly through stomata, direct penetration attempts were also scored. Moreover, papilla formation turned out to be very rare. Assays for changes in peroxydase (PO), glutathione-S-transferase (GST) and lipoxygenase (LOX) activities allowed us to compare their levels in the five French wheat cultivars regarding to their resistance and/or tolerance towards M. graminicola infection. PO and GST were correlated to necrosis probably as a consequence of detoxification and LOX was related to some of the germination process steps. We also showed that significant differences for several biochemical parameters exist between the studied cultivars in non inoculated conditions but these differences were less important in the presence of the fungus.

International audience; Using a multilevel Cox model, the association between socioeconomic and geographical aggregate variables and survival was investigated in 81 268 patients with digestive tract cancer diagnosed in the years 1980-1997 and registered in 12 registries in the French Network of Cancer Registries. This association differed according to cancer site: it was clear for colon (relative risk (RR)=1.10 (1.04-1.16), 1.10 (1.04-1.16) and 1.14 (1.05-1.23), respectively, for distances to nearest reference cancer care centre between 10 and 30, 30 and 50 and more than 90 km, in comparison with distance of less than 10 km; P-trend=0.003) and rectal cancer (RR=1.09 (1.03-1.15), RR=1.08 (1.02-1.14) and RR=1.12 (1.05-1.19), respectively, for distances between 10 and 30 km, 30 and 50 km and 50 and 70 km, P-trend=0.024) (n=28 010 and n=18 080, respectively) but was not significant for gall bladder and biliary tract cancer (n=2893) or small intestine cancer (n=1038). Even though the influence of socioeconomic status on prognosis is modest compared to clinical prognostic factors such as histology or stage at diagnosis, socioeconomic deprivation and distance to nearest cancer centre need to be considered as potential survival predictors in digestive tract cancer.

We present a case of right sided blindness caused by a cavernous carotid artery aneurysm in a 17-year-old patient presenting with an Alagille syndrome. The diagnosis was made by magnetic resonance imaging and confirmed by angiography. This aneurysm was treated successfully with endovascular placement of detachable balloons. Cerebral vascular malformations are rarely reported in association with this syndrome. We discuss the clinical presentation, diagnosis, treatment and detection of this type of abnormality.