NS3 protease polymorphism and natural resistance to protease inhibitors in French patients infected with HCV genotypes 1–5

Background: Resistant HCV populations may pre-exist in patients before NS3 protease inhibitor therapy and would likely be selected under specific antiviral pressure. The higher prevalence and lower rate of response to treatment associated with HCV genotype 1 infections has led to drug discovery efforts being focused primarily on enzymes produced by this genotype. Protease inhibitors may also be useful for non-genotype-1-infected patients, notably for non-responders.Methods: We investigated the prevalence of dominant resistance mutations and polymorphism in 298 HCV protease-inhibitor-naive patients infected with HCV genotypes 1, 2, 3, 4 or 5. Genotype-specific NS3 primers were designed to amplify and sequence the NS3 protease gene. Results: None of the 233 analysed sequences contained major telaprevir (TVR) or boceprevir (BOC) resistance mutations (R155K/T/M, A156S/V/T and V170A). Some substitutions (V36L, T54S, Q80K/R, D168Q and V170T) linked to low or moderate decreases in HCV sensitivity to protease inhibitors were prevalent according to genotype (between 2% and 100%). Other than genotype signature mutations at positions 36, 80 and 168, the most frequent substitution was T54S (4 genotype 1 and 2 genotype 4 sequences). All genotype 2–5 sequences had the non-genotype-1 signature V36L mutation known to confer low-level resistance to both TVR and BOC. Conclusions: We have developed an HCV protease NS3 inhibitor resistance genotyping tool suitable for use with HCV genotypes 1–5. Polymorphism data is valuable for interpreting genotypic resistance profiles in cases of failure of anti-HCV NS3 protease treatment

The Mediterranean Decision Support System for Marine Safety dedicated to oil slicks predictions

In the Mediterranean sea the risk from oil spill pollution is high due to the heavy traffic of merchant vessels for transporting oil and gas, especially after the recent enlargement of the Suez canal and to the increasing coastal and offshore installations related to the oil industry in general. The basic response to major oil spills includes different measures and equipment. However, in order to strengthen the maritime safety related to oil spill pollution in the Mediterranean and to assist the response agencies, a multi-model oil spill prediction service has been set up, known as MEDESS-4MS (Mediterranean Decision Support System for Marine Safety). The concept behind the MEDESS-4MS service is the integration of the existing national ocean forecasting systems in the region with the Copernicus Marine Environmental Monitoring Service (CMEMS) and their interconnection, through a dedicated network data repository, facilitating access to all these data and to the data from the oil spill monitoring platforms, including the satellite data ones, with the well established oil spill models in the region. The MEDESS-4MS offer a range of service scenarios, multi-model data access and interactive capabilities to suite the needs of REMPEC (Regional Marine Pollution Emergency Response Centre for the Mediterranean Sea) and EMSA-CSN (European Maritime Safety Agency-CleanseaNet)

Développement d'une nouvelle grandeur de référence pour les traitements en conditions stéréotaxiques: le produit dose-surface

International audienceL’utilisation de petits faisceaux en radiothérapie stéréotaxique conduit à s’éloigner significativement des conditions d’étalonnage usuels des dosimètres, fondée sur la notion de dose absorbée en un point (IAEA TRS 398 Actuellement, l’approche adoptée est d’introduire des facteurs de correction lors du commissioning de l’accélérateur (IAEA TRS 483). Pour palier ce problème, le LNHB a proposé d’introduire, au niveau métrologique une nouvelle grandeur dosimétrique, qui s’affranchit des limites du concept de dose ponctuelle, fondée sur l’utilisation d’un détecteur plus grand que la section du faisceau le Produit Dose Surface (PDS

Tracking the extent of the South Pacific Convergence Zone since the early 1600s

[ 1] The South Pacific Convergence Zone (SPCZ) is the largest and most persistent spur of the Intertropical Convergence Zone. At the southeastern edge of the SPCZ near 170 degrees W and 15 degrees - 20 degrees S a surface ocean salinity frontal zone exists that separates fresher Western Pacific Warm Pool water from saltier and cooler waters in the east. This salinity front is known to shift east and west with the phase of the El Nino Southern Oscillation. We have generated subannually resolved and replicated coral oxygen isotopic time series from Fiji ( 17 degrees S, 179 degrees E) and Rarotonga (21.5 degrees S, 160 degrees W) that have recorded interannual displacements of the salinity front over the last 380 years and also indicate that at lower frequencies the decadal mean position of the salinity front, and eastern extent of the SPCZ, has shifted east-west through 10 degrees to 20 degrees of longitude three times during this interval. The most recent and largest shift began in the mid 1800s as the salinity front progressively moved eastward and salinity decreased at both sites. Our results suggest that sea surface salinity at these sites is now at the lowest levels recorded and is evidence for an unprecedented expansion of the SPCZ since the mid 1800s. The expansion of the SPCZ implies a gradual change in the South Pacific to more La Nina-like long-term mean conditions. This observation is consistent with the ocean thermostat mechanism for the Pacific coupled ocean-atmosphere system, whereby exogenous heating of the atmosphere would result in greater warming in the western Pacific and a greater east-west surface temperature gradient

A comparison of kinematic evidence for tropical cells in the Atlantic and Pacific oceans.

International audienceKinematic evidence for the existence of Tropical Cells (TC) in the Atlantic Ocean is offered. Mean sections of meridional velocity, its horizontal divergence and vertical velocity are estimated from twelve available sections centered at about 35°W. Of the twelve sections, six were occupied in March and April, thus there is a boreal spring bias to the observations. Equatorial upwelling and offequatorial downwelling, between 3°N and 6°N, represent the southern and northern boundaries of a northern hemisphere TC. Uncertainties for the estimates of average quantities are large. However, favorable comparisons with observational representations of Pacific TC's provide support for the existence of a northern hemisphere Atlantic TC

Lactobacilli intra-tracheal administration protects from Pseudomonas aeruginosa pulmonary infection in mice - a proof of concept

WOS:000501544400007International audienceThe spreading of antibiotic resistance is a major public health issue, which requires alternative treatments to antibiotics. Lactobacilli have shown abilities to prevent pneumonia in clinical studies when given by oral route, certainly through the gut-lung axis involvement. Rationally, respiratory administration of lactobacilli has been developed and studied in murine model, to prevent from respiratory pathogens. It allows a direct effect of probiotics into the respiratory system. To our knowledge, no study has ever focused on the effect of probiotic intra-respiratory administration to prevent from Pseudomonas aeruginosa (PA) pneumonia, a major respiratory pathogen associated with high morbidity rates. In this study, we evaluated the beneficial activity of three Lactobacillus strains (Lactobacillus fermentum K.C6.3.1E, Lactobacillus zeae Od.76, Lactobacillus paracasei ES.D.88) previously screened by ourselves and known to be particularly efficient in vitro in inhibiting PAO1 virulence factors. Cytotoxic assays in alveolar epithelial cell line A549 were performed, followed by the comparison of two lactobacilli prophylactic protocols (one or two administrations) by intra-tracheal administration in a C57BL/6 murine model of PA pneumonia. A549 cells viability was improved from 23 to 75% when lactobacilli were administered before PAO1 incubation, demonstrating a protective effect (P\textless0.001). A significant decrease of 2 log of PAO1 was observed 4 h after PAO1 instillation (3x 10(6) cfu/mouse) in both groups receiving lactobacilli (9x 10(6) cfu/mouse) compared to PAO1 group (P\textless0.05). One single prophylactic administration of lactobacilli significantly decreased the secretion by 50% in bronchoalveolar lavages of interleukin (IL)-6 and tumour necrosis factor-a compared to PAO1. No difference of secretion was observed for the IL-10 secretion, whatever the prophylactic study design. This is the first study highlighting that direct lung administration of Lactobacillus strains protect against PA pneumonia. Next step will be to decipher the mechanisms involved before developing this novel approach for human applications