Loss of vascular CD34 results in increased sensitivity to lung injury

Survival during lung injury requires a coordinated program of damage limitation and rapid repair. CD34 is a cell surface sialomucin expressed by epithelial, vascular and stromal cells that promotes cell adhesion, coordinates inflammatory cell recruitment, and drives angiogenesis. To test whether CD34 also orchestrates pulmonary damage and repair, we induced acute lung injury in wild type (WT) and Cd34-/- mice by bleomycin (BLM) administration. We found that Cd34-/- mice displayed severe weight loss and early mortality compared to WT controls. Despite equivalent early airway inflammation to WT mice, CD34-deficient animals developed interstitial edema and endothelial delamination, suggesting impaired endothelial function. Chimeric Cd34-/- mice reconstituted with WT hematopoietic cells exhibited early mortality compared to WT mice reconstituted with Cd34-/- cells, supporting an endothelial defect. CD34-deficient mice were also more sensitive to lung damage caused by influenza infection, showing greater weight loss and more extensive pulmonary remodeling. Together our data suggest that CD34 plays an essential role in maintaining vascular integrity in the lung in response to chemical- and infection-induced, tissue damage

Point de vue des parents autour de la consultation de leur adolescent chez le médecin généraliste dans les deux Savoies : étude qualitative par entretiens semi-dirigés

Introduction: Adolescence is a transitional period. Parents are often with their teenagers during the consultation and preserve a prominent place. Objective: Exploring the parents point of view around the consultation of their adolescents to the General Practitioner, in order to give them the most appropriate place and also to enhance the doctor-parent partnership in adolescent medical care. Methods : Qualitative survey by semi-structured individual interviews of 14 to 17 years old-boy teenager’s parents and 13 to 16 years old-girl teenager’s parents, in these two Savoys area. Results: The period of secondment was more or less well felt by parents. The General Practitioner seemed to be seen as an indispensable assistance for teenagers and parents in this process. For parents, the General Practitioner had to be able to put the teenagers in confidence. They wanted them to help their adolescent to draw out what is in their hearts and to invest their own medical care. Even if for parents, the General Practitioner was not the first resort organically, psychologically or in prevention, they expected him to be competent and able to offer an adolescent comprehensive care. Discussion: General Practitionners are invited to inquire principles of docteur-patient confidentiality and to give informations to the teenagers about it during the consultation. Giving informations about prevention topics to parents can be a way to improve adolescent health. Conclusion: Even if the teenager’s pace has to be respected, the General Practitioner is invited to take initiatives during the consultation in order to empower teenagers and to assist parents in steping down.Introduction : L’adolescence marque la transition vers l’autonomie médicale. Durant cette période, le parent, souvent présent lors des consultations de médecine générale, garde une place prépondérante auprès de l’adolescent. Objectif : Explorer le point de vue des parents autour de la consultation de leur adolescent chez le médecin généraliste. Méthode : Etude qualitative par entretiens individuels semi-dirigés de parents de garçons de 14 à 17 ans et de filles de 13 à 16 ans, dans les deux Savoies. Les verbatims ont été analysés par 2 chercheuses pour obtenir une triangulation des données. Résultats : Les 15 entretiens ont mis en avant l’autonomisation médicale de l’enfant était pour beaucoup de parents un objectif de l’adolescence malgré le détachement maternel difficile qu’il implique. Selon le parent, le médecin devait mettre en confiance l’adolescent par ses compétences humaines et relationnelles. Les parents se considéraient confidents et conseillers avant le médecin pour la prévention. Ils attendaient néanmoins du médecin qu’il soit compétent pour prendre en charge l’adolescent dans sa globalité. Discussion : S’informer du secret médical pour en retransmettre les principes à l’adolescent de manière à libérer sa parole, et donner des informations en matière de prévention au parent autant qu’à l’adolescent sont des pistes que les médecins sont invités à suivre. Conclusion : Selon les parents, le médecin doit mettre l’adolescent en confiance pour l’aider à s’autonomiser sur le plan médical. Si le rythme de l’adolescent doit être respecté, le médecin doit prendre des initiatives en consultation pour le responsabiliser et aider son parent à passer la main

Contested legitimacy for anthropologists involved in medical humanitarian action: experiences from the 2014-2016 West Africa Ebola epidemic.

The growing involvement of anthropologists in medical humanitarian response efforts has laid bare the moral and ethical consequences that emerge from humanitarian action. Anthropologists are well placed to examine the social, political, cultural and economic dimensions that influence the spread of diseases, and the ways in which to respond to epidemics. Anthropologists are also, with care, able to turn a critical lens on medical humanitarian response. However, there remains some resistance to involving anthropologists in response activities in the field. Drawing on interviews with anthropologists and humanitarian workers involved in the 2014-2016 West African Ebola epidemic, this paper reveals the complex roles taken on by anthropologists in the field and reveals how anthropologists faced questions of legitimacy vis-à-vis communities and responders in their roles in response activities, which focused on acting as 'firefighters' and 'cultural brokers' as well as legitimacy as academic researchers. Whilst these anthropologists were able to conduct research alongside these activities, or draw on anthropological knowledge to inform response activities, questions also arose about the legitimacy of these roles for anthropological academia. We conclude that the process of gaining legitimacy from all these different constituencies is particular to anthropologists and reveals the role of 'giving voice' to communities alongside critiquing medical humanitarianism. Whilst these anthropologists have strengthened the argument for the involvement of anthropologists in epidemic response this anthropological engagement with medical humanitarianism has revealed theoretical considerations more broadly for the discipline, as highlighted through engagement in other fields, especially in human rights and global health

Audiological Outcomes and Associated Factors after Pediatric Cochlear Reimplantation

Cochlear implants are the most common and successful sensory neuroprosthetic devices. However, reimplantation can be required for medical reasons, device failure, or technological upgrading. Resolving the problem driving the intervention and offering stable or better audiological results are the main challenges. We aimed to analyze the success rate of this intervention and to identify factors influencing speech perception recovery after reimplantation in the pediatric population. We retrospectively collected the causes and the outcomes of 67 consecutive reimplantations in one cochlear implant center over 30 years. Reimplantation resolved the cause without recurrence for 94% of patients. The etiology of deafness, time since implantation, indication of reimplantation, sex, and age did not influence word discrimination test scores in silence, 3 years after surgery. However, adherence to a speech rehabilitation program was statistically associated with gain in perception scores: +8.9% [−2.2; +31.0%] versus −19.0% [−47.5; −7.6%] if no or suboptimal rehabilitation was followed (p = 0.0037). Cochlear reimplantation in children is efficient and is associated with predictable improvement in speech perception, 3 years after intervention. However, good adherence to speech rehabilitation program is necessary and should be discussed with the patient and parents, especially for the indication of reimplantation for technological upgrading

The "one-step" Bean pod mottle virus (BPMV)derived vector is a functional genomics tool for efficient overexpression of heterologous protein, virus-induced gene silencing and genetic mapping of BPMV R-gene in common bean (Phaseolus vulgaris L.)

Background: Over the last two years, considerable advances have been made in common bean (Phaseolus vulgaris L.) genomics, especially with the completion of the genome sequence and the availability of RNAseq data. However, as common bean is recalcitrant to stable genetic transformation, much work remains to be done for the development of functional genomics tools adapted to large-scale studies. Results: Here we report the successful implementation of an efficient viral vector system for foreign gene expression, virus-induced gene silencing (VIGS) and genetic mapping of a BPMV resistance gene in common bean, using a "one-step" BPMV vector originally developed in soybean. With the goal of developing this vector for high-throughput VIGS studies in common bean, we optimized the conditions for rub-inoculation of infectious BPMV-derived plasmids in common bean cv. Black Valentine. We then tested the susceptibility to BPMV of six cultivars, and found that only Black Valentine and JaloEEP558 were susceptible to BPMV. We used a BPMV-GFP construct to detect the spatial and temporal infection patterns of BPMV in vegetative and reproductive tissues. VIGS of the PHYTOENE DESATURASE (PvPDS) marker gene was successfully achieved with recombinant BPMV vectors carrying fragments ranging from 132 to 391 bp. Finally, we mapped a gene for resistance to BPMV (R-BPMV) at one end of linkage group 2, in the vicinity of a locus (I locus) previously shown to be involved in virus resistance. Conclusions: The " one-step" BPMV vector system therefore enables rapid and simple functional studies in common bean, and could be suitable for large-scale analyses. In the post-genomic era, these advances are timely for the common bean research communit

Aire-dependent genes undergo Clp1-mediated 3'UTR shortening associated with higher transcript stability in the thymus

International audienceThe ability of the immune system to avoid autoimmune disease relies on tolerization of thymocytes to self-antigens whose expression and presentation by thymic medullary epithelial cells (mTECs) is controlled predominantly by Aire at the transcriptional level and possibly regulated at other unrecognized levels. Aire-sensitive gene expression is influenced by several molecular factors, some of which belong to the 3’end processing complex, suggesting they might impact transcript stability and levels through an effect on 3’UTR shortening. We discovered that Aire-sensitive genes display a pronounced preference for short-3’UTR transcript isoforms in mTECs, a feature preceding Aire’s expression and correlated with the preferential selection of proximal polyA sites by the 3’end processing complex. Through an RNAi screen and generation of a lentigenic mouse, we found that one factor, Clp1, promotes 3’UTR shortening associated with higher transcript stability and expression of Aire-sensitive genes, revealing a post-transcriptional level of control of Aire-activated expression in mTECs

Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma

International audienceBACKGROUND:Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis.OBJECTIVE:We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients.PATIENTS AND METHODS:Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences.RESULTS:At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04-6.56; p = 0.04).CONCLUSIONS:This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies

Outbreak of Amazonian Toxoplasmosis: A One Health Investigation in a Remote Amerindian Community

International audienceBackground: Toxoplasma gondii is a parasite of worldwide importance but its burden in indigenous communities remains unclear. In French Guiana, atypical strains of T. gondii originating from a complex rainforest cycle involving wild felids have been linked to severe infections in humans. These cases of Amazonian toxoplasmosis are sporadic and outbreaks are rarely described. We report on the investigation of an outbreak of acute toxoplasmosis in a remote Amerindian village. We discuss the causes and consequences of this emergence.Methods: In May 2017, during the rainy season and following an episode of flooding, four simultaneous cases of acute toxoplasmosis were serologically confirmed in two families living the village. Other non-diagnosed cases were then actively screened by a medical team along with epidemiological investigations. Inhabitants from nine households were tested for T. gondii antibodies and parasite DNA by PCR when appropriate. Samples of water, cat feces and cat rectal swabs, soil, and meat were tested for T. gondii DNA by PCR. Positive PCR samples with sufficient DNA amounts were genotyped using 15 microsatellite markers.Results: Between early May and early July 2017, out of 54 tested inhabitants, 20 cases were serologically confirmed. A fetus infected at gestational week 10 died but other cases were mild. Four patients tested positive for parasite DNA and two identical strains belonging to an atypical genotype could be isolated from unrelated patients. While domestic cats had recently appeared in the vicinity, most families drank water from unsafe sources. Parasite DNA was recovered from one water sample and nine soil samples. Three meat samples tested positive, including wild and industrial meat.Conclusions: The emergence of toxoplasmosis in such a community living in close contact with the Amazon rainforest is probably multifactorial. Sedentary settlements have been built in the last few decades without providing safe water sources, increasing the risk of parasite circulation in cases of dangerous new habits such as cat domestication. Public health actions should be implemented in these communities such as safe water supply, health recommendations, and epidemiological surveillance of acute toxoplasmosis. A “One Health” strategy of research involving medical anthropology, veterinary medicine, and public health needs to be pursued for a better understanding of the transmission routes and the emergence of this zoonosis

Epidémie de toxoplasmose amazonienne en territoire amérindien : analyse d'une situation d'émergence

International audienc