Hand, foot and mouth disease (HFMD) and herpangina (HA) are frequently caused by several distinct serotypes belonging to the human enterovirus A species (HEVA). Enterovirus 71 is considered as a ...significant public health threat because of rare but fatal neurological complications. A sentinel surveillance system involving paediatricians from Clermont-Ferrand (France) was set up to determine the clinical and epidemiological characteristics of HFMD/HA associated with enterovirus infections. A standardized report form was used to collect demographic and clinical data. Throat or buccal specimens were obtained prospectively and tested for the presence of enteroviruses. The frequency of HEVA serotypes was determined by genotyping. Phylogenetic relationships were analysed to identify potential new virus variants. From 1 April to 31 December 2010, a total of 222 children were enrolled. The predominant clinical presentation was HA (63.8%) and this was frequently associated with clinical signs of HFMD (48%). An enterovirus infection was diagnosed in 143 (64.4%) patients and serotype identification was achieved in 141/143 (98.6%). The predominant serotypes were coxsackievirus A10 (39.9%) and A6 (28%), followed by coxsackievirus A16 (17.5%) and enterovirus 71 (6.3%). Fever was observed in 115 (80.4%) children. No patient had neurological complications. Coxsackievirus A10 and A6 strains involved in the outbreak were consistently genetically related with those detected earlier in Finland and constituted distinct European lineages. Although several enterovirus serotypes have been involved in HFMD/HA cases, the outbreak described in this population survey was caused by coxsackievirus A6 and coxsackievirus A10, the third dual outbreak in Europe in the last 3 years.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The degradation of mechanical properties of closed-cell elastomeric foams in fatigue and its link with the cellular structure is still poorly understood. To clarify this, we performed interrupted and ...continuous cyclic compression tests on EVA closed-cell foams used in running shoes. The 3D cellular structures of tested samples was analyzed before, during and after fatigue tests using X-ray microtomography and digital volume correlation. Interrupting the cycling allows the observation of the cell flattening along the compression axis with both plastic bending and an increase of tears/holes of cell walls. These two fatigue-induced defects are suspected to play a strong contribution on the fatigue properties of the foam at the sample scale and may explain the partial recovery of the initial mechanical property of foams while restarting cycling.
•The fatigue of EVA foams is studied via finite strain cyclic compression tests.•The evolving microstructures are analyzed in 3D with X-ray microtomography.•The loss of mechanical properties is due to the creeping and tearing of cell walls.•Interrupting the cycling leads to partial recovery of the sample shape•Restarting the cycling leads to recover the trends observed during continuous cycling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Background
Tiludronate is a bisphosphonate drug marketed to treat different bone conditions in horses.
Objectives
The goal of this study was to measure the plasma concentrations of ...tiludronate in a population of race and sport horses under field conditions, and using pharmacokinetic population modelling, to estimate detection times for doping control.
Study design
Prospective cohort.
Methods
This study was conducted under field conditions on 39 race or sport horses diagnosed with bone conditions based on a lameness examination and treated with tiludronate. Each horse received 1 mg/kg of tiludronate (Tildren®) intravenously (i.v.). Blood samples (from 1 to 4 per horse with a total of 93 samples) were collected around 10, 20, 30, 40 and 50 days after tiludronate administration. Tiludronate was quantified by HPLC/ESI‐MSn. Tiludronate concentrations were analysed using nonlinear mixed‐effects modelling (population approach). Monte Carlo simulations were then used to compute a prediction interval to estimate the corresponding quantile of horses predicted to have concentrations below some potential screening limits.
Results
This study highlighted pharmacokinetic differences between healthy experimental horses and the population of horses being treated in the field as well as the effect of level of training on plasma tiludronate. Different detection times were computed corresponding to different possible screening limits.
Main limitations
The number of horses in each group was limited, and the specific disease being treated with tiludronate is unknown.
Conclusions
This population pharmacokinetic study on tiludronate will enable racing and other sports authorities to provide a detection time reflecting field conditions for the medication control of tiludronate. More generally, our study design and the data modelling serve as an example of how to generate detection times directly from the target horse population rather than from experimental horses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Human echovirus types 6 (E-6) and 30 (E-30) cause seasonal epidemics of aseptic meningitis. These two enteroviruses are frequently observed in co-circulation, an epidemiological pattern that is ...prerequisite for the occurrence of dual infections, which can lead to recombination between co-infecting virus strains. Viral sequences were determined at loci 1D (VP1 capsid protein) and 3CD (non structural proteins) in 49 E-6 strains recovered in a single geographical region in France from 1999 to 2007, during the epidemiological survey of enterovirus infections. They were compared with previously recorded sequences of E-30 strains to investigate their evolutionary histories and possible recombination patterns. Phylogenetic analyses identified two distinct E-6 populations and different subpopulations. Assuming a relaxed molecular clock model and a Bayesian skyline demographic model in coalescent analyses with the BEAST program, the substitution rate in E-6 was estimated at 8.597×10−3 and 6.252×10−3 substitution/site/year for loci 1D and 3CD respectively. Consistent estimates of divergence times (tMRCA) were obtained for loci 1D and 3CD indicating that two distinct E-6 populations originated in 1997 and 1999. Incongruent phylogenetic patterns inferred for the two loci were indicative of recombination events between the two populations. Phylogenies including the E-30 3CD sequences showed close genetic relationships between E-6 and discrete E-30 subpopulations. Recombination breakpoints were located with statistical significance in E-6 and E-30 genomes. Estimates of tMRCA of phylogenetic recombinant clades indicated directional genetic transfers from E-30 to E-6 populations and their co-divergence over the time period studied.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Due to their excellent specific mechanical properties, closed cell elastomeric foams are the main element in the soles of running shoes to absorb repetitive shocks from strides and to release a ...maximum of the absorbed energy. However, these cellular materials are gradually damaged. To enhance their mechanical durability by slowing their damage kinetics, it is critical to understand their mechanical behaviour in fatigue. The objective of this work is thus to clarify the link between the microstructure and the fatigue properties of five commercial elastomeric foams used in the midsoles of running shoes. The 3D cellular structures of each foam were finely analysed using X-ray microtomography. Foam samples were then subjected to cyclic compression which were close to running conditions. During cycling, samples exhibited a rapid densification associated with noticeable decreases of (i) the stress levels required to deform them as well as (ii) the cushioning and (iii) the rebound properties. We show that the two midsoles filled with micro-sized mineral fillers present the highest specific mechanical properties during the first compression cycle and during fatigue. However, their damage kinetics and rebound properties could probably be improved by tuning the fillers-matrix compatibility. The lightest foam, being very porous and presenting process-induced tortuous cell walls, is the best cushioning system but exhibits high damage kinetics. The densest foam presents poor specific mechanical properties, but very slow damage kinetics. Its double hierarchical architecture probably prevents the occurrence of micro-cracks in the cell walls.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Depuis une dizaine d’années, l’utilisation des Bandelettes Sous-Urétrales (BSU) a nettement diminué en raison de certaines complications observées telles que les douleurs chroniques, l’exposition de ...prothèse, la récidive de l’incontinence ou l’apparition de fistules pelviennes. Un nouveau cadre de loi encadre désormais cette pratique depuis la controverse suscitée par les prothèses voie basse. Néanmoins, il existe peu d’études s’intéressant à l’évolution à long terme des BSU, avec notamment la prise en compte des effets indésirables et du taux de reprises chirurgicales nécessaires au long cours. L’objectif de notre étude était d’évaluer le taux de retrait et/ou de réintervention à long terme des patientes ayant bénéficiées d‘une première pose de BSU et de rechercher les potentiels facteurs de risque de réintervention. Notre étude permettra de mieux évaluer le pronostic des patientes opérées d’une BSU à la lumière des changements actuels.
Il s’agit d’une étude sur bases médico-administrative incluant 217 326 patientes âgées de plus de 18 ans, ayant eu la pose d’une BSU pour incontinence urinaire d’effort (IUE) du 1er janvier 2013 au 31 décembre 2021, dans des établissements de santé publics et privés. Les patientes ont eu au moins un an de suivi jusqu’au 31 décembre 2022. Le critère de jugement principal était le taux de retrait (partiel ou totale) de la BSU et les critères de jugement secondaires étaient le taux de repose de BSU sans retrait et le taux de reprise chirurgicale autre pour IUE. Une analyse de survie et un model de Cox ont été réalisés pour évaluer les facteurs de risque de retrait/réopération. Les facteurs suivants ont été évalués : type de BSU (rétropubienne ou transobturatrice), obésité, tabagisme et/ou alcoolisme, hypertension artérielle, diabète, dyslipidémie, anémie, insuffisance rénale ou cardiaque, accidents vasculaires cérébraux, prolapsus des organes pelviens, hémorragie, maladie neurogène, troubles hématologiques cancer, maladie de Crohn, affection respiratoire ou hépatique chronique.
La population étudiée était composée de 217 326 femmes ayant bénéficiées d’une première pose de BSU, dont 5 851 ablations et 9 521 réopérations sans ablation. L’âge médian était de 56 ans 47–68. La durée médiane de suivi était de 2,4 ans (IQR 1 jour–5,2 ans). Il y avait 46 768 BSU par voie rétropubienne (TVT) et 170 558 par voie transobturatrice (TOT). La majorité des retraits de BSU ont eu lieu au cours de la première année (58 %) et 40 % au cours des six premiers mois. Les retraits qui ont eu lieu entre 5 et 10 ans représentent moins de 8 % de l’ensemble des retraits de BSU. Le taux de retrait de BSU était de 1,6 % à 1 an, 2,5 % à 5 ans et 2,7 % à 10 ans. Le risque de retrait diminuait avec l’âge : 3,5 % pour les 18–39 ans ; 2,8 % pour les 50–59 ans et 2,4 % pour les 70 ans à 10 ans. Le risque de retrait à 10 ans après insertion d’une TOT (2,6 %) était statistiquement inférieur au risque après insertion d’un TVT (3 %), p<0,0001. Parmi l’ensemble des comorbidités évaluées l’intoxication alcooliques et/ou tabagique et l’obésité étaient des facteurs de risque de retrait de BSU, avec respectivement risques relatifs de 1,2 (p=0,0004) et 1,1 (p<0,03). Le type de BSU était aussi significatif avec un RR. 0,89 pour les TOT (p<0,0001). Le taux de repose de BSU sans retrait était de 2,2 % à 1 an, 4 % à 5 ans et 4,5 % à 10 ans. Le risque de repose à 10 ans après TOT (4,3 %) était statistiquement inférieur au risque après TVT (5,2 %), p<0,0001. Le taux de réinterventions, toutes confondues (y compris les retraits de BSU) était de 3,7 % à 1 an, 6,4 % à 5 ans, 7,1 % à 10 ans. L’ensemble des complications (érosion, infection, saignement et douleur) étaient de 5,5 % ; avec un risque plus élevé après TVT (7,7 %) qu’après TOT (5,0 %).
La majorité des reinterventions (58 %) survenaient la première année. Le taux de retrait à 10 ans après une première pose de BSU était de 2,7 % et le taux de repose était de 4,5 % à 10 ans. Les taux de retrait étaient moins élevés après un TOT qu’un TVT, de même que les taux de reprise chirurgicale pour incontinence urinaire d’effort. Cela peut s’expliquer par le fait que les opérations pour retrait de BSU sont techniquement plus difficiles lorsqu’il s’agit d’un TOT que d’un TVT. Cependant, ces résultats contredisent les études précédentes concernant les taux de reprise chirurgicale qui retrouvaient des taux plus élevés en cas de TOT. Concernant les taux de complications entre un TVT et un TOT, nous avons également trouvé plus de complications après TVT qu’avec TOT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A comprehensive set of 443 1D gene sequences (encoding the VP1 capsid protein) was analyzed to investigate the phylogenetic relationships and evolutionary patterns among strains of human echovirus 30 ...(E30; genus Enterovirus, family
Picornaviridae) characterized over 50 years. Maximum-likelihood (ML) phylogenetic trees of complete and nonredundant 1D gene sequences (total length
=
876 nucleotides) showed evidence of distinct lineages related to the isolation period of virus strains. Virus transportation was confirmed as a major epidemiological factor in the appearance of epidemics since recurrence of aseptic meningitis outbreaks in a given geographic area was associated with distinct E30 variants detected earlier in distant regions. Detection of the codon changes associated with E30 evolution was investigated with methods implemented in the Datamonkey web server. Evolution of the 1D gene was dominated by continual negative (purifying) selection against nonsynonymous substitutions at most codon sites, as determined by d
N/d
S ratio. Amino acid polymorphism was maintained at a limited number of sites (10/292) in the VP1 protein (within loops connecting β strands and C-terminus). Amino acid changes are allowed at these sites because they are likely exposed on the virion particle and nonsynonymous substitutions are observed in the corresponding codons because negative selection is relaxed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Human enterovirus 71 (EV-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. Uncertainty persists regarding the ...circulation of virus populations in several geographical areas and the timescale of their dissemination. We determined EV-71 sequences at loci 1D (VP1 capsid protein) and 3CD (non-structural proteins) in 86 strains recovered in Austria, France and Germany and performed an evolutionary genetic study of extant virus populations. Phylogenetic analyses positioned 78 of the 86 sequences within two clades among subgenogroups C1 and C2. A minor sequence cluster was assigned to subgenogroup C4. Analyses incorporating the available sequences estimated the substitution rate in genogroup C at 3.66 x 10(-3) and 4.46 x 10(-3) substitutions per site year(-1) for loci 1D and 3CD, respectively, assuming a relaxed molecular-clock model for sequence evolution. Most of the 'European' strains belonged to clades C1b and C2b, which originated in 1994 95 % confidence interval (CI), 1992.7-1995.8 and 2002 (95 % CI, 2001.6-2003.8), respectively. Estimates of divergence times for locus 3CD were consistent with those measured for locus 1D. Intertwining between clades representing EV-71 subgenogroups and clades corresponding to other enterovirus types (notably early coxsackievirus A prototype strains) in the 3CD phylogeny is highly indicative of ancestral recombination events. Incongruent phylogenetic patterns estimated for loci 1D and 3CD show that a single tree cannot model the epidemic history of circulating EV-71 populations. The evolutionary timescale of genogroup C estimated for both loci was measured only in decades, indicating recent dissemination.
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