201 research outputs found
An in vitro evaluation of the efficacy of tedizolid: implications for the treatment of skin and soft tissue infections
Skin and soft tissue infections (SSTI) are among the most commonly occurring infections and evidence suggests that these are increasing world-wide. The aetiology is diverse, but Staphylococcus aureus predominate and these are often resistant to antimicrobials that were previously effective. Tedizolid is a new oxazolidinone-class antibacterial indicated for the treatment of adults with SSTI caused by Gram-positive pathogens, including S. aureus. The aim of this study was to evaluate the in vitro efficacy of tedizolid in comparison to other clinically used antibacterials against antibiotic sensitive- and resistant-staphylococci, grown in planktonic cultures and as biofilms reflecting the growth of the microorganism during episodes of SSTI. Against a panel of 66 clinical staphylococci, sensitivity testing revealed that a lower concentration of tedizolid was required to inhibit the growth of staphylococci compared to linezolid, vancomycin and daptomycin; with the tedizolid MIC being 8-fold (S. aureus) or 4-fold (S. epidermidis) below that obtained for linezolid. In addition, cfr+ linezolid-resistant strains remained fully susceptible to tedizolid. Against S. aureus biofilms, 10ĂMIC tedizolid was superior or comparable with 10ĂMIC comparator agents in activity, and superior to 10ĂMIC linezolid against those formed by S. epidermidis (65 vs. 33% reduction, respectively). Under flow-conditions both oxazolidinones at 10ĂMIC statistically out-performed vancomycin in their ability to reduce the viable cell count within a S. aureus biofilm with fewer the 12% of cells surviving compared to 63% of cells. In conclusion, tedizolid offers a realistic lower-dose alternative agent to treat staphylococcal SSTI, including infections caused by multi-drug resistant strains
Antagonisme de lactococcus garvieae vis-à -vis de Staphylococcus aureus : étude physiologique et transcriptomique des mécanismes
Among strategies aiming to control the growth of spoilage microorganisms in food, the biopreservation is based on the inhibitory capacities of other microorganisms and presents a considerable variety of opportunities. A good understanding of the molecular and physiologic mechanisms underlying the antagonism of the preservative microorganism against the spoilage bacterium is also required. This thesis aimed to characterize the antagonism of L. garvieae N201 dairy strain against S. aureus strains combining in vitro strategies: genomic, transcriptomic (targeted concerning S. aureus, global concerning L. garvieae) and phenotypic. The involvement of hydrogen peroxide (H2O2) produced by L. garvieae under high aeration was already known. Although H2O2 concentration was undetectable using spectrophotometry method, it was produced by L. garvieae under low aeration at sufficient concentration to induce S. aureus inhibition. L. garvieae H2O2 -synthesis genes (poxB, sodA) seemed constitutively expressed whatever the aeration level. L. garvieae H2O2-degradation (katA, sodA, ahpC / ahpF) genes were overexpressed under low aeration, suggesting their involvement in control of autogenous H2O2 level. In parallel, three other mechanisms may be involved in this antagonistic relationship: i) the repression of S. aureus stress-response genes (clpC, ctsR, dnaK) by L. garvieae and / or under high aeration, ii) the repression of S. aureus cell-division genes (mraZ, mraW and probably the dcw cluster) by L. garvieae, iii), the production by L. garvieae of an extracellular effector which has to be characterized. Additionally, L. garvieae can modulate the expression of S. aureus major virulence genes, repressing those coding for enterotoxins under low aeration. Thus, L. garvieae N201 turned out to be an interesting candidate for biopreservative applications. However, its safety for humans should be approved and its antagonism against S. aureus has to be investigated in food matrices. The data resulting from this work may be used to study other interactions between other valuable species and in other ecosystems.Parmi les stratĂ©gies visant Ă contrĂŽler la croissance de microorganismes pathogĂšnes dans un aliment, la bioprĂ©servation qui sâappuie sur lâutilisation des capacitĂ©s inhibitrices dâautres microorganismes offre une grande diversitĂ© dâopportunitĂ©s. Il est cependant nĂ©cessaire de comprendre les mĂ©canismes molĂ©culaires et physiologiques rĂ©gissant lâantagonisme du microorganisme protecteur vis-Ă -vis de la bactĂ©rie indĂ©sirable. Lâobjectif de cette thĂšse Ă©tait de caractĂ©riser lâantagonisme de L. garvieae N201, isolĂ© de fromage, vis-Ă -vis de souches de S. aureus par des approches in vitro : gĂ©nomique, transcriptomique (ciblĂ©e concernant S. aureus, globale concernant L. garvieae) et phĂ©notypique. Un acteur avait dĂ©jĂ Ă©tĂ© identifiĂ© : le peroxyde dâhydrogĂšne (H2O2) produit par L. garvieae sous un niveau dâaĂ©ration Ă©levĂ©. Lors de ces travaux de thĂšse, il a Ă©tĂ© montrĂ© que le peroxyde dâhydrogĂšne serait Ă©galement produit par L. garvieae sous une faible aĂ©ration en quantitĂ© faible (indĂ©tectable par spectrophotomĂ©trie) mais suffisante pour induire une inhibition de S. aureus. Les gĂšnes de production du H2O2 de L. garvieae (poxB, sodA) seraient exprimĂ©s constitutivement quel que soit le niveau dâaĂ©ration. Les gĂšnes de dĂ©gradation du H2O2 (katA, sodA, ahpC / ahpF) seraient plutĂŽt surexprimĂ©s sous une faible aĂ©ration, suggĂ©rant leur rĂŽle dans un mode de contrĂŽle de la concentration en H2O2 autogĂšne par L. garvieae. En parallĂšle, trois autres mĂ©canismes potentiellement impliquĂ©s dans lâantagonisme ont Ă©tĂ© mis en Ă©vidence : i) la rĂ©pression de gĂšnes de rĂ©ponse au stress (clpC, ctsR, dnaK) de S. aureus par L. garvieae et lâaĂ©ration, ii) la rĂ©pression de gĂšnes de division cellulaire de S. aureus (mraZ, mraW, potentiellement le cluster dcw) par L. garvieae, iii) la production dâun effecteur extracellulaire par L. garvieae dont la nature reste Ă caractĂ©riser. AjoutĂ© Ă cela, la prĂ©sence de L. garvieae modulerait lâexpression des principaux gĂšnes de virulence de S. aureus, rĂ©primant ceux codant pour les entĂ©rotoxines sous une faible aĂ©ration. Ainsi, la souche L. garvieae N201 sâest rĂ©vĂ©lĂ©e ĂȘtre une candidate intĂ©ressante comme agent de bioprĂ©servation. Cependant, son innocuitĂ© pour lâHomme devra ĂȘtre vĂ©rifiĂ©e et son antagonisme sur S. aureus devra ĂȘtre Ă©valuĂ© en matrice alimentaire. Les donnĂ©es gĂ©nĂ©rĂ©es ainsi que la dĂ©marche dĂ©veloppĂ©e pourront ĂȘtre utilisĂ©es afin dâĂ©tudier des interactions entre dâautres espĂšces dâintĂ©rĂȘt et dans des Ă©cosystĂšmes diffĂ©rents
Approche stratigraphique des temps Gravettiens : lâĂ©clairage aquitain
Le cadre spatio-temporel du gravettien est relativement large. En effet, la pĂ©riode gravettienne a sans doute durĂ© plusieurs milliers dâannĂ©es, au moins 6 000 â annĂ©es 14 C â rĂ©parties de part et dâautre de 25 000 BP. Quant au territoire, il sâĂ©tale dâouest en est sur toute lâEurope, ce qui pose la question des corrĂ©lations Ă grande distance. Dans ce travail, nous avons utilisĂ© les moyens et mĂ©thodes de la stratigraphie pour tenter dâĂ©tablir des liens chronologiques entre entitĂ©s gravettiennes de lâouest et du centre de lâEurope. Pour cela, nous nous sommes intĂ©ressĂ©s tout dâabord Ă la rĂ©gion Aquitaine et avons recherchĂ© des phĂ©nomĂšnes environnementaux marqueurs. Ces derniers ont servi de points dâancrage entre entitĂ©s stratigraphiques ouest et centre europĂ©ennes. Les datations physiques, prises en compte dans un deuxiĂšme temps, ne contredisent pas lâhypothĂšse de corrĂ©lation proposĂ©e. Elles conduisent nĂ©anmoins Ă mettre en garde contre lâutilisation dâune maille chronologique trop fine.The Gravettian was widely distributed in time and space. Temporally, it lasted at least 6000 radiocarbon years, centering on 25,000 BP. Spatially, it extended across all of Europe, posing the challenge of correlating assemblages across vast distances. We have used stratigraphic methods in an attempt to establish chronological ties between Gravettian assemblages in western and central Europe. Using the record from the Aquitaine, we have constructed a series of environmental horizon markers which serve as anchor points among stratigraphic entities in western and central Europe. Our hypothesized correlations are not contradicted by the radiocarbon dates available for the Gravettian. Those dates do, however, suggest that we should be wary of building highly precise links among far-flung Gravettian assemblages
Jules Verne 2.0, renewal of a large wind tunnel facility
International audienceThe paper aims at showing the evolution of methods to design a large wind tunnel. The current Jules Verne facility was designed with a scale model of the wind tunnel which enabled hot wire local wind speed measurements. The new facility is designed according a numerical modelling approach which parameters were validated by PIV measurements in the reduced scale physical model
The Aurignacian and Gravettian in northern Aquitaine: the contribution of Flageolet I
The site of Le Flageolet (BĂ©zenac, Dordogne) contains two rock shelters excavated between 1966 and 1993. Le Flageolet I, the subject of this paper, opens to the west. On the bedrock, a first lithostratigraphic unit yielded three Aurignacian archaeostrata in a mass of very large blocks that collapsed before or during the earliest human occupations. A second overlying lithostratum contained at least six Gravettian archaeostrata. Due to the complexity of this archaeostratigraphy, we conceived and applied a method of excavation based on the three-dimensional recording of all artefacts with a maximum dimension over 1.5 cm, the use of artefact drawings at a scale of 1/5, and feature distributions, and the concomitant production of narrow vertical artefact projections along various frontal and sagittal axes. This method allowed for tight control over the definition and integrity of artefact levels. Analyses of the resulting assemblages show that the traditional regional cultural âmarkersâ do not have the unambiguous chronological significance attributed to them in the past based on interpretations from excavations at La Ferrassie, Pataud, Caminade, and Roc-de-Combe. The large ungulate mammal biostratigraphy enabled us to chronologically position all the Aurignacian and Gravettian faunal assemblages from Le Flageolet I in relation to those from other Aquitaine sites; the faunal remains allow for the identification of particular environmental conditions that may be considered as âkey events,â marking certain specific periods during the development of the Aurignacian-Gravettian sequence. Based on radiocarbon ages, several major Aquitaine sites, including Le Flageolet I, have been situated on the NGRIP climatic curve, thereby providing a chronological context independent of stone tool technology and typology. Based on all of this, a chronological-cultural model can be proposed that considers functional variation as an important influence on Aurignacian and Gravettian assemblage composition at Le Flageolet I and elsewhere. Since 1982, numerous publications on Le Flageolet I have contributed to a lively debate on the Western European Early Upper Palaeolithic. This paper addresses some recently expressed criticisms
LâAurignacien et le Gravettien du nord de lâAquitaine : la contribution du Flageolet I (BĂ©zenac, Dordogne, France)
Le site du Flageolet (BĂ©zenac, Dordogne) comporte deux abris sous roche fouillĂ©s entre 1966 et 1993. Le Flageolet I, objet de cet article, est orientĂ© vers lâouest. Sur le sol rocheux, une premiĂšre unitĂ© lithostratigraphique a livrĂ© trois niveaux aurignaciens dans une structure dâaccueil composĂ©e de blocs rocheux volumineux correspondant Ă lâeffondrement de lâabri prĂ©cĂ©dant ou contemporain des premiĂšres occupations. La seconde unitĂ© a livrĂ© plus de six niveaux gravettiens. En raison de la complexitĂ© de lâarchĂ©ostratigraphie, nous avons conçu et appliquĂ© une mĂ©thode de fouille basĂ©e sur lâenregistrement tridimensionnel de tous les vestiges lithiques et osseux de plus de 1,5 cm mis au jour, sur le relevĂ© planimĂ©trique au 1/5e des vestiges et des structures anthropiques ou naturelles et sur la rĂ©alisation concomitante de projections gĂ©omĂ©trales frontales et sagittales de faible Ă©paisseur. Cette mĂ©thode a permis dâexercer un contrĂŽle taphonomique sur lâhomogĂ©nĂ©itĂ© des nappes de vestiges. Lâanalyse des industries lithiques des ensembles aurignaco-gravettiens montre que les principaux marqueurs culturels nâont pas la signification chronologique qui leur avait Ă©tĂ© attribuĂ©e prĂ©cĂ©demment sur la base de lâinterprĂ©tation univoque des rĂ©sultats des fouilles des abris de La Ferrassie, Pataud, Caminade et Roc de Combe. Les recherches fondĂ©es sur la biostratigraphie des grands mammifĂšres ongulĂ©s ont permis de situer dans le temps les ensembles aurignaciens et gravettiens du Flageolet I relativement Ă ceux dâautres sites aquitains ; elles ont aussi conduit Ă la mise en Ă©vidence dâenvironnements particuliers qui peuvent ĂȘtre considĂ©rĂ©s comme des Ă©vĂ©nements clĂ©s, marqueurs de certaines pĂ©riodes au cours desquelles sâest dĂ©veloppĂ©e la sĂ©quence aurignaco-gravettienne. Ă partir de leurs datations radiocarbones, plusieurs sites majeurs dâAquitaine ont Ă©tĂ© situĂ©s relativement Ă la courbe NGRIP fournissant ainsi un cadre chronologique indĂ©pendant des donnĂ©es techno-typologiques. Sur cette base, une interprĂ©tation alternative au modĂšle chrono-culturel a Ă©tĂ© alors proposĂ©e faisant intervenir une variabilitĂ© dâordre fonctionnel applicable au Flageolet I ainsi quâĂ bien dâautres sites aurignaco-gravettiens. Depuis 1982, de nombreuses publications sur le Flageolet I ont contribuĂ© Ă un dĂ©bat vigoureux sur les premiĂšres industries du PalĂ©olithique supĂ©rieur de lâEurope de lâOuest. Cet article rĂ©pond Ă©galement Ă quelques critiques rĂ©cemment exprimĂ©es.The site of Le Flageolet (BĂ©zenac, Dordogne) contains 2 rockshelters excavated between 1966 and 1993. Le Flageolet I, the subject of this paper, opens to the west. On the bedrock, a first lithostratigraphic unit yielded 3 Aurignacian archaeostrata within a mass of very large breakdown blocks that fell before or during the earliest human occupations. A second overlying lithostratum contained at least six Gravettian archaeostrata. Because of the complexity of this archaeostratigraphy, we conceived and applied a method of excavation based on three-dimensional recording of every artifact over 1,5 cm in maximum dimension, the use of scale drawings at 1/5 of artifact and feature distributions, and the concomitant production of narrow vertical artifact projections along various frontal and sagittal axes. This method allowed for fine control over the definition and integrity of artifact levels. Analyses of the resulting assemblages show that the traditional regional cultural âmarkersâ do not have the unambiguous chronological significance attributed to them in the past based on interpretations from excavations at La Ferrassie, Pataud, Caminade, and Roc de Combe. Large ungulate mammal biostratigraphy allows chronological placement for all Aurignacian and Gravettian faunal assemblages from Le Flageolet I in relation to those from other Aquitaine sites ; the faunal remains permit the identification of particular environmental conditions that may be considered as âkey events,â marking certain specific periods during the development of the Aurignacian-Gravettian sequence. Based on radiocarbon ages, several major Aquitaine sites, including Le Flageolet I, have been situated within the NGRIP climatic curve, thereby providing a chronological context independent of stone tool technology and typology. Based on all of this, a chronological-cultural model can be proposed that sees functional variation as an important influence on Aurignacian and Gravettian assemblage composition at Le Flageolet I and elsewhere. Since 1982, numerous publications on Le Flageolet I have contributed to a vigorous debate on the Western European Early Upper Paleolithic. This paper answers some recently expressed criticisms
Development of a preclinical model of donation after circulatory determination of death for translational application
BACKGROUND: Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs. METHODS: We used Large White pigs weighing between 45 and 55Â kg. After 30Â minutes of potassium-induced cardiac arrest, the descending thoracic aorta was clamped and ANOR set up between the inferior vena cava and the abdominal aorta for 4Â hours. Hemodynamic, respiratory and biochemical parameters were collected. Blood gasometry and biochemistry analysis were performed during the ANOR procedure. RESULTS: Six ANOR procedures were performed. The surgical procedure is described and intraoperative parameters and biological data are presented. Pump flow rates were between 2.5 and 3Â l/min. Hemodynamic, respiratory, and biochemical objectives were achieved under reproducible conditions. Interestingly, animals remained hemodynamically stable following the targeted protocol. Arterial pH was controlled, and natremia and renal function remained stable 4Â hours after the procedure was started. Decreased hemoglobin and serum proteins levels, concomitant with increased lactate dehydrogenase activity, were observed as a consequence of the surgery. The serum potassium level was increased, owing to the extracorporeal circulation circuit. CONCLUSIONS: Our ANOR model is the closest to clinical conditions reported in the literature and will allow the study of the systemic and abdominal organ impact of this technique. The translational relevance of the pig will permit the determination of new biomarkers and protocols to improve DCD donor management
Matrix Isolation Infrared Spectroscopic and Theoretical Study of the Interaction of Water with Dimethyl Methylphosphonate
Matrix isolation infrared spectroscopy has been combined with theoretical calculations for the characterization of the 1:1 hydrogen-bonded complex between H2O and dimethyl methylphosphonate (DMMP). The symmetric O-H stretching mode was observed to shift 203 cm-1 to lower energy upon hydrogen bond formation, while a 32 cm-1 blue shift was noted for the H-O-H bending mode of the H2O subunit in the complex. These values compare extremely well with the (unscaled) shifts of -203 and +32 cm-1, respectively, that were calculated theoretically at the MP2/6-31+G** level. Additional perturbed modes of the DMMP subunit were observed, shifted relative to the parent band position. The greatest perturbation was to the P=O stretching mode near 1270 cm-1, where a shift of -17 cm-1 was observed (-21 cm-1 calculated theoretically). This suggests that the site of hydrogen bonding in the complex is at the P=O group, in agreement with theoretical calculations. The binding energy ÎE° for the 1:1 complex was calculated to be -7.7 kcal/mol
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