Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients

Myasthenia Gravis (MG) is mediated by autoantibodies against acetylcholine receptors that cause loss of the receptors in the neuromuscular junction. Eculizumab, a C5-inhibitor, is the only approved treatment for MG that mechanistically addresses complement-mediated loss of nicotinic acetylcholine receptors. It is an expensive drug and was approved despite missing the primary efficacy endpoint in the Phase 3 REGAIN study. There are two observations to highlight. Firstly, further C5 inhibitors are in clinical development, but other terminal pathway proteins, such as C7, have been relatively understudied as therapeutic targets, despite the potential for lower and less frequent dosing. Secondly, given the known heterogenous mechanisms of action of autoantibodies in MG, effective patient stratification in the REGAIN trial may have provided more favorable efficacy readouts. We investigated C7 as a target and assessed the in vitro function, binding epitopes and mechanism of action of three mAbs against C7. We found the mAbs were human, cynomolgus monkey and/or rat cross-reactive and each had a distinct, novel mechanism of C7 inhibition. TPP1820 was effective in preventing experimental MG in rats in both prophylactic and therapeutic dosing regimens. To enable identification of MG patients that are likely to respond to C7 inhibition, we developed a patient stratification assay and showed in a small cohort of MG patients (n=19) that 63% had significant complement activation and C7-dependent loss of AChRs in this in vitro set up. This study provides validation of C7 as a target for treatment of MG and provides a means of identifying patients likely to respond to anti-C7 therapy based on complement-activating properties of patient autoantibodies

Etude et applications d'un generateur a plasma

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 82244 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Apparent competition or apparent mutualism? An analysis of the influence of rose bush strip management on aphid population in wheat field

Apparent competition, mediated by a shared predator, plays a key role in conservation biological control. Appropriate agroecosystems management may favour this type of indirect interaction. In that context, our aim was to test the effect of rose bush [Rosa rugosa (Thunb.)] strips on the building up of aphid populations and of their natural enemies in adjacent cereal habitats. Several aphid species are currently found on Rosa sp. including Metopolophium dirhodum (Walker) for which it is a primary host. Aphid predators and parasitoids may build their populations on the aphid population present on Rosa sp. and later on migrate to wheat field during the cereal aphid infestation. Moreover, the flowers of the rose bushes may provide a source of nectar and pollen to these natural enemies. Our experiment was conducted in three rose margin wheat plots with a strip of rose bushes of R. rugosa and three control plots. Plots were compared during 2 years (2003 and 2004). Aphid, parasitoid and predator densities were recorded from May to the harvest of wheat on rose bushes and in wheat. In 2003, the aphid densities were moderate but in 2004, the population of aphid was very high. Even if predator and parasitoids arrived earlier in rose margin field than in control ones, the presence of rose bushes did not influence the aphid population within the field. Metopolophium dirhodum did not seem to migrate from the rose bushes to wheat. The level of parasitism was weak in rose bushes and the natural enemy population was not different in rose margin wheat and in control plots. The causes of the lack of efficiency of this type of management are discussed as well as the high aphid population in wheat in 2004

Involvement of odorant cues in the process of superparasitism avoidance

The ability to avoid superparasitism provides a selective advantage to parasitoid females, allowing them to avoid depositing eggs in lower quality host. We observed in a Y-olfactometer that generalist aphid parasitoids, Aphidius ervi and Aphidius rhopalosiphi (Hymenoptera, Braconidae), were more attracted toward non-parasitized than parasitized Sitobion avenae (Hemiptera, Aphididae) colonies. We collected the odors released from healthy aphids and aphids parasitized for 2 and 6 days using an electronic nose. Sitobion avenae alarm pheromone, (E)-ß-farnesene (EßF), was the only chemical identified, and was found in lower quantities in parasitized aphids. Both parasitoid species provided pronounced electrical depolarizations to EßF in electroantennography (EAG), and both were attracted to the latter compound in the Y-olfactometer. Parasitoid attraction was known to be guided by a variety of odorant cues released by plants and hosts, and our results support the hypothesis that the aphid alarm pheromone acts as a kairomone for A. ervi and A. rhopalosiphi

Improvement in the cold storage of aphidius ervi : Hymenoptera : Aphidiinae

Biological control is beginning to be more commonly used, especially in greenhouses. The inundatory release of insects, especially parasitoids, requires a!thorough knowledge of their biology and of mass-rearing techniques. Moreover, to synchronize releases with host presence, the parasitoids have to be kept in cold storage. However, cold storage may lead to a!decrease in the viability of the parasitoids,in particular their survival, mobility and sex ratio. The aim of this study was to determine the best temperature at which to keep parasitoid mummies in cold storage. The parasitoid Aphidius ervi Haliday (Hymenoptera, Braconidae) and two of its host aphids, Sitobion avenae and Acyrthosiphon pisum, were used. It is concluded that the mummies can be kept for a!maximum of two weeks at 7 °C without emergence of adults and for seven weeks at 2 °C without emergence or mortality. Moreover, storage of the mummies at 7 or 2 °C does not a"ect fertility. However, parasitoid pupae in A. pisum mummies su"ered a!higher mortality and took longer to complete their development. The practical implications of these results are discussed

Kingella kingae bone and joint infections

peer reviewedWe report six cases of children with probable or confirmed Kingella kingae bone and joint infections (BJI) and discuss the role of this pathogen in the pediatric population. The advent of Polymerase Chain Reaction (PCR) led to the recognition of the importance of Kingella kingae in several human diseases, particularly in BJI affecting children aged 6 to 48 months. Kingella kingae infections in children have most often a good prognosis provided that the diagnosis is discussed, appropriate diagnostic methods are performed and effective antibiotics are prescribed

Influence of environmental and anthropogenic factors on the composition, concentration and spatial distribution of microplastics: A case study of the Bay of Brest (Brittany, France)

The concentration and spatial distribution of microplastics in the Bay of Brest (Brittany, France) was investigated in two surveys. Surface water and sediment were sampled at nine locations in areas characterized by contrasting anthropic pressures, riverine influences or water mixing. Microplastics were categorized by their polymer type and size class. Microplastic contamination in surface water and sediment was dominated by polyethylene fragments (PE, 53–67%) followed by polypropylene (PP, 16–30%) and polystyrene (PS, 16–17%) microparticles. The presence of buoyant microplastics (PE, PP and PS) in sediment suggests the existence of physical and/or biological processes leading to vertical transfer of lightweight microplastics in the bay. In sediment (upper 5 cm), the percentage of particles identified by Raman micro-spectroscopy was lower (41%) than in surface water (79%) and may explain the apparent low concentration observed in this matrix (0.97 ± 2.08 MP kg−1 dry sediment). Mean microplastic concentration was 0.24 ± 0.35 MP m−3 in surface water. We suggest that the observed spatial MP distribution is related to proximity to urbanized areas and to hydrodynamics in the bay. A particle dispersal model was used to study the influence of hydrodynamics on surface microplastic distribution. The outputs of the model showed the presence of a transitional convergence zone in the centre of the bay during flood tide, where floating debris coming from the northern and southern parts of the bay tends to accumulate before being expelled from the bay. Further modelling work and observations integrating (i) the complex vertical motion of microplastics, and (ii) their point sources is required to better understand the fate of microplastics in such a complex coastal ecosystem

Prise en charge du cancer de l’endomètre métastatique et/ou en rechute. Recommandations 2020 pour la pratique clinique (Colloque de Nice-Saint Paul de Vence)

International audienc

Évaluation quantitative de l’effet sur le passage aux urgences et les hospitalisations d’un dispositif départemental innovant de prise en charge des situations de crise durant l’adolescence en Haute-Garonne, France

International audienceObjectivesCrisis situations are common during adolescence. Current data show that adolescents in crisis are either directly referred to hospital psychiatric emergency rooms, or they make an appointment for a specialized consultation, in a medical-psychological center (CMP), in a medical-psychological-pedagogical center (CMPP), or with a private practitioner. The Departmental Reactive System for Adolescents was implemented in 2017 in the French department of Haute-Garonne to provide adolescents in crisis an immediate specialized psychiatric consultation including on-going support for three months. Our objective was to measure the effect of the implementation of this health system organization (HSO) on the evolution of the annual incidence of emergency room visits and hospitalizations of adolescents for psychiatric reasons at the Toulouse University Hospital, the sole facility for such care in Haute-Garonne.MethodsWe conducted a quasi-experimental study comparing the evolution, before and after the implementation of the DDRA31, the annual incidence rates of emergency room visits (pediatric and adult) and hospitalizations related to mental health at the Toulouse University Hospital for adolescents aged 12 to 17 years of age, residing in Haute-Garonne, from 2014 to 2019. Factors associated with the risk of hospitalization were analyzed using mixed-effects logistic regression to measure the effect of the system, over time, with the specific year as the primary explanatory variable, adjusted for sex and age.ResultsFrom 2014 to 2019, 6 686 emergency room visits by 4 245 adolescents took placefor psychiatric motives or diagnostics. The annual incidence rate of emergency department visits related to mental health was stable from 14.0 (95 % CI: 13.2–14.9), per 100 adolescents in 2014 to 13.9 (95 % CI: 13.2–14.7) in 2019, with a higher incidence rate for girls and adolescents aged from 15 to 17 years old. The main reasons for emergency room visits were behavioral problems or agitation, drug intoxications or suicide attempts, and drug or alcohol use or abuse. The annual incidence of hospitalizations decreased significantly since 2017, from 38.3 (95 % CI: 34.1–42.8) per 100 adolescents in 2014 to 24.2 (95 % CI: 21.2–27.4) per 100 adolescents in 2019. This decrease was shown for both males and females but only for adolescents aged from 15 to 17 years old, from 21.8 (CI 95 %: 17.9–26.1) in 2014 to 2.6 (CI 95 %: 1.5–4.1) in 2019. Modeling of the hospitalization risk showed a significant reduction from 2017 onward inclusive with an odds ratio ranging from 0.63 (95 % CI: 0.49–0.80) in 2017 to 0.52 (95 % CI: 0.41–0.67) in 2019.DiscussionThe fact that an impact of the HSO was found only for adolescents aged 15 to 17 years of age could indicate a selective effectiveness depending on age possibly caused by differences in physician attitudes depending on the age of the patient. The chronology of changes in hospitalization rates after a visit to the emergency room corresponded to the period when the HSO was implemented, whereas hospitalization rates were stable over the three years prior to its implementation. The main limitations of our study were the absence of data regarding emergency department diagnoses and discharge modes for the year 2019 and the lack of a temporal perspective.ConclusionOur study did not show any significant effect of the HSO on the annual incidence of emergency room visits related to mental health, but there was a possible effect on reducing the yearly incidence rate and the risk of hospitalization of adolescents in psychiatric services following an emergency room visit. The implementation of reactive ambulatory structures could therefore reduce the demand on hospitalization services that are under pressure.ObjectifsLes situations de crise sont fréquentes à l’adolescence. Le Dispositif Départemental Réactif pour Adolescents (DDRA31) a été implanté en 2017, en Haute-Garonne, pour offrir rapidement, aux adolescents en crise, une consultation spécialisée de psychiatrie avec un accompagnement de trois mois. Notre objectif était de mesurer l’effet de l’implantation de ce dispositif sur l’évolution de l’incidence annuelle des consultations aux urgences et hospitalisations des adolescents pour motif psychiatrique au CHU de Toulouse, guichet hospitalier unique de leur prise en charge en Haute-Garonne.MéthodesNous avons conduit une étude quasi expérimentale mesurant l’évolution avant-après l’implantation du DDRA31, l’incidence annuelle des passages aux urgences (pédiatriques et adultes) et d’hospitalisation pour motif psychiatrique au CHU de Toulouse parmi la file active annuelle de tous les adolescents âgés de 12 à 17 ans révolus, résidant en Haute-Garonne, de 2014 à 2019. Les facteurs associés au risque d’hospitalisation ont été analysés par régression logistique à effet mixte pour mesurer l’effet du dispositif au cours du temps, avec l’année comme variable explicative principale, ajusté sur le sexe et l’âge.RésultatsDe 2014 à 2019, 6686 passages aux urgences, réalisés par 4245 adolescents ont été observés. Le taux annuel d’incidence de passage aux urgences pour motif psychiatrique était stable, passant de 14,0 (IC 95 % : 13,2–14,9) pour 100 adolescents en 2014, à 13,9 (IC 95 % : 13,2–14,7) pour 100 adolescents en 2019. L’incidence annuelle des hospitalisations a diminué significativement de 38,3 (IC 95 % : 34,1–42,8) pour 100 adolescents en 2014 à 24,2 (IC 95 % : 21,2–27,4) pour 100 adolescents en 2019. La modélisation du risque d’hospitalisation montrait une réduction significative à partir de 2017, avec un rapport de cotes passant de 0,63 (IC 95 % : 0,49–0,80) en 2017 à 0,52 (IC 95 % : 0,41–0,67) en 2019.ConclusionNous n’avons pas montré d’effet du dispositif sur l’incidence annuelle du passage aux urgences pour motif psychiatrique mais un effet possible sur la réduction du risque d’hospitalisation en psychiatrie, suite à un passage aux urgences. La mise en place de structures ambulatoires réactives pourrait diminuer la sollicitation de services d’hospitalisation sous tension