27 research outputs found
Chikungunya Virus Neutralization Antigens and Direct Cell-to-Cell Transmission Are Revealed by Human Antibody-Escape Mutants
Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop “groove” as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis
3D-Printing to Plan Complex Transcatheter Paravalvular Leaks Closure
International audienceBackground: Percutaneous closure of paravalvular leak (PVL) has emerged as an alternative to surgical management in selected cases. Achieving complete PVL occlusion, while respecting prosthesis function remains challenging. A multimodal imaging analysis of PVL morphology before and during the procedure is mandatory to select an appropriate device. We aim to explore the additional value of 3D printing in predicting device related adverse events including mechanical valve leaflet blockade, risk of device embolization and residual shunting.Methods: From the FFPP registries (NCT05089136 and NCT05117359), we included 11 transcatheter PVL closure procedures from three centers for which 3D printed models were produced. Cardiac CT was used for segmentation for 3D printed models (3D-heartmodeling, Caissargues, France). Technology used a laser to fuse very fine powders (TPU Thermoplastic polyurethane) into a final part-laser sintering technology (SLS) with an adapted elasticity. A simulation on 3D printed model was performed using a set of occluders.Results: PVLs were located around aortic prostheses in six cases, mitral prostheses in four cases and tricuspid ring in one case. The device chosen during the simulation on the 3D printed model matched the one implanted in eight cases. In the three other cases, a similar device type was chosen during the procedures but with a different size. A risk of prosthesis leaflet blockade was identified on 3D printed models in four cases. During the procedure, the occluder was removed before release in one case. In another case the device was successfully repositioned and released. In two patients, leaflet impingement was observed post-operatively and surgical device removal had to be performed.Conclusion: In a case-series of complex transcatheter PVL closure procedures, hands-on simulation testing on 3D printed models proved its usefulness to plan and facilitate these challenging procedures
The French Addictovigilance Network Clinical Assessment: Z-Drugs, True False Twins
International audienceINTRODUCTION: In France, an addictovigilance network is responsible for evaluating drug dependence, by drawing on pharmacoepidemiological studies, clinical studies and by assessing healthcare professionals' reports on problematic consumption. METHODS: The aim of this study was to determine whether zolpidem and zopiclone have different dependence profiles, based on healthcare professionals' reports, and to identify various consumer dependence profiles among zolpidem users and among zopiclone users. Dependence in reports was assessed using the EGAP scale; a scale developed using the DSM diagnostic dependence criteria. RESULTS: The comparison of dependence profiles for zolpidem and zopiclone showed differences both in total EGAP score and EGAP item positivity. The descriptive analysis showed that EGAP scores were higher for zolpidem than for zopiclone, suggesting more severe problematic consumption with zolpidem. For zolpidem 2 subpopulations of consumers were identified, with one subpopulation's consumption being more severe than the other, with a significantly higher total EGAP score and more harmful consequences. No subpopulation was highlighted for zopiclone. CONCLUSION: These results were in favour of a higher prevalence of physical and compulsive signs of dependence and of harmful consequences of dependence, with zolpidem than with zopiclone
Development of new wood treatments combining boron impregnation and thermo modification: effect of additives on boron leachability
International audienc
Molecular Simulation of Adsorption and Transport in Hierarchical Porous Materials
Adsorption and transport in hierarchical
porous solids with micro-
(∼1 nm) and mesoporosities (>2 nm) are investigated by molecular
simulation. Two models of hierarchical solids are considered: microporous
materials in which mesopores are carved out (model A) and mesoporous
materials in which microporous nanoparticles are inserted (model B).
Adsorption isotherms for model A can be described as a linear combination
of the adsorption isotherms for pure mesoporous and microporous solids.
In contrast, adsorption in model B departs from adsorption in pure
microporous and mesoporous solids; the inserted microporous particles
act as defects, which help nucleate the liquid phase within the mesopore
and shift capillary condensation toward lower pressures. As far as
transport under a pressure gradient is concerned, the flux in hierarchical
materials consisting of microporous solids in which mesopores are
carved out obeys the Navier–Stokes equation so that Darcy’s
law is verified within the mesopore. Moreover, the flow in such materials
is larger than in a single mesopore, due to the transfer between micropores
and mesopores. This nonzero velocity at the mesopore surface implies
that transport in such hierarchical materials involves slippage at
the mesopore surface, although the adsorbate has a strong affinity
for the surface. In contrast to model A, flux in model B is smaller
than in a single mesopore, as the nanoparticles act as constrictions
that hinder transport. By a subtle effect arising from fast transport
in the mesopores, the presence of mesopores increases the number of
molecules in the microporosity in hierarchical materials and, hence,
decreases the flow in the micropores (due to mass conservation). As
a result, we do not observe faster diffusion in the micropores of
hierarchical materials upon flow but slower diffusion, which increases
the contact time between the adsorbate and the surface of the microporosity
Films of Tunable ZnO Nanostructures Prepared by a Surfactant-Mediated Soft Synthesis Route
Films of ZnO nanostructures were prepared by a soft chemical synthesis route from ZnO crystal seeds in aqueous medium, in the presence of alkylsulfates of different chain length acting as structure-directing agents. Films of arrayed single crystal ZnO nanorods were formed with short alkyl sulfates, from C6 to C8 alkylene chains, while hybrid lamellar ZnO with a platelike morphology were obtained with C10 to C18 alkyl sulfates. In the case of the short alkyl sulfates, due to the interaction between the sulfate groups and the Zn2+ planes of the ZnO structure, the growth along the c axis is partially inhibited and smaller aspect ratios of the nanorods are obtained than in alkylsulfate-free conditions. In the case of the hybrid lamellar ZnO structures which consist in ZnO layers intercalated with alkylsulfate bilayers, the structural characteristics depend on the alkylene chain length. Basal spacings increase linearly with the chain length, while the plate size decreases dramatically when the chain length exceeds C14. The different characteristics of these ZnO nanostructured films allow modifying their optical properties
Dexterity in the Acute Phase of Stroke: Impairments and Neural Substrates.
Stroke can impair manual dexterity, leading to loss of independence following incomplete recovery. Enhancing our understanding of dexterity impairment may improve neurorehabilitation. The study aimed to measure dexterity components in acute stroke patients with and without hand motor deficits, compare them to those of healthy controls (HC), and to explore the neural substrates involved in specific components of dexterity. We used the Dextrain Manipulandum to quantify fine finger force control, finger selection accuracy, coactivation, and reaction time (RT). Dexterity was evaluated twice (2 days apart) in 74 patients and 14 HC. Voxel-Lesion-Symptom-Mapping (VLSM) was used to analyze the relationship between tissue damage and dexterity. Due to severe paresis or fatigue, 24 patients could not perform these tasks. In 50 patients (included 4.6 ± 3.3 days post-stroke), finger force control improved ( < .001), as it did in HC ( = .03) who performed better than patients on both evaluations. Accuracy of finger selection did not improve significantly in any group, but the HC performed better on both evaluations. Unexpectedly, coactivation was better in patients than in HC at D3 ( = .03). There were no between-group differences in RT. VLSM showed that damage to the superior temporal gyrus (STG) impaired finger force control while damage to the posterior limb of the internal capsule (PLIC) impaired finger selectivity. Acute stroke affecting the STG or PLIC impaired selective components of dexterity. Patients with mild to moderate impairment showed better finger force control and accuracy selection within 48 hours, suggesting the feasibility of detecting early dexterity improvements