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Listeria monocytogenes (Lm) is a foodborne pathogen and the etiological agent of listeriosis. This facultative intracellular Gram-positive bacterium has the ability to colonize the intestinal lumen, cross the intestinal, blood-brain and placental barriers, leading to bacteremia, neurolisteriosis and maternal-fetal listeriosis. Lm is a model microorganism for the study of the interplay between a pathogenic microbe, host tissues and microbiota in vivo. Here we review how animal models permissive to Lm-host interactions allow deciphering some of the key steps of the infectious process, from the intestinal lumen to the crossing of host barriers and dissemination within the host. We also highlight recent investigations using tagged Lm and clinically relevant strains that have shed light on within-host dynamics and the purifying selection of Lm virulence factors. Studying Lm infection in vivo is a way forward to explore host biology and unveil the mechanisms that have selected its capacity to closely associate with its vertebrate hosts.

Introduction Les particularites anatomiques des os de l’avant-bras rendent leur reconstruction difficile. Notre objectif etait de rapporter les modalites operatoires et resultats de la technique de la membrane induite appliquee a des lesions osseuses traumatiques de l’avant-bras. Materiel et methodes Nous avons evalue retrospectivement une serie de 13 patients operes entre 2010 et 2017. Le premier temps a consiste en un debridement du foyer lesionnel et en la mise en place d’une entretoise en ciment et d’une osteosynthese adaptee. L’anatomie du cadre antebrachial devait etre restauree. Le second temps, effectue 6 semaines plus tard, a consiste en une autogreffe spongieuse iliaque, aprSs ablation de l’entretoise en ciment. Les criteres d’evaluation etaient la consolidation osseuse radiologique, la survenue de reprises chirurgicales, et les mobilites du poignet postoperatoires. Resultats Les 13 patients etaient des hommes âges en moyenne de 39 ans (18–67 ans). La duree moyenne du suivi etait de 2,5 ans. Il s’agissait de pseudarthrose dans 11 cas de perte de substance osseuse traumatique dans 2 cas. Six patients avaient une infection preoperatoire identifiee. Trois des patients etaient en echec d’une precedente cure de pseudarthrose avec apport osseux. La longueur d’os reconstruite mesurait au maximum 12 cm. La consolidation osseuse a ete obtenue chez 12 des 13 patients au delai moyen de 5 mois (3–8 mois). Le deces du dernier patient dans les suites a interrompu son suivi. Deux patients ont necessite une reprise chirurgicale : pour osteotomie d’accourcissement de l’ulna (1 cas), et complement de reconstruction tendineuse (1 cas). L’arc moyen de prono-supination etait de 123° en moyenne (55–180°). L’arc moyen en flexion extension etait de 106 degres (90–130°) Conclusion La technique de la membrane induite est une technique de reconstruction fiable, techniquement adaptee aux reconstructions du cadre antebrachial. Niveau de preuve IV ; etude retrospective.

International audience; Infections of the central nervous system are among the most serious infections1,2, but the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest infections of the central nervous system3,4. Although immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known about the bacterial factors that underlie the neuroinvasion of Lm. Here we develop a clinically relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6 inoculated in a humanized mouse model of infection7, and we show that the bacterial surface protein InlB protects infected monocytes from Fas-mediated cell death by CD8+ T cells in a manner that depends on c-Met, PI3 kinase and FLIP. This blockade of specific anti-Lm cellular immune killing lengthens the lifespan of infected monocytes, and thereby favours the transfer of Lm from infected monocytes to the brain. The intracellular niche that is created by InlB-mediated cell-autonomous immune resistance also promotes Lm faecal shedding, which accounts for the selection of InlB as a core virulence gene of Lm. We have uncovered a specific mechanism by which a bacterial pathogen confers an increased lifespan to the cells it infects by rendering them resistant to cell-mediated immunity. This promotes the persistence of Lm within the host, its dissemination to the central nervous system and its transmission.

Resume Introduction Le traitement des pseudarthroses humerales avec ou sans perte de substance osseuse est complexe et comporte un taux de complications et d’echecs non negligeables. Rares sont les series qui s’attardent sur la prise en charge des echecs de cure de pseudarthrose humerale. Objectif L’hypothese de ce travail est que l’utilisation de la membrane induite associee a une osteosynthese interne avec deux temps operatoires permet d’obtenir une consolidation de maniere constante dans le traitement des pseudarthroses rebelles de l’humerus. Materiel et methodes L’etude portait sur 15 patients, d’âge median 46,6 ans. En moyenne, les patients presentaient une pseudarthrose humerale depuis 24 mois et avaient deja ete operes a 3 reprises pour cure de pseudarthrose. Il existait une perte de substance chez 7 patients, elle depassait 5 cm dans 2 cas. Six patients avaient deja eu une paralysie radiale. Resultats La consolidation a ete obtenue chez tous les patients. La duree moyenne de consolidation etait de 4,6 mois. Dix patients ont eu une transposition du nerf radial, 6 parmi eux ont presente une paralysie radiale motrice apres la transposition. Ils ont tous recupere entre 2 et 5 mois. Un cas d’infection superficielle et 1 serome ont ete releves. Discussion La technique de la membrane induite permet d’obtenir une consolidation osseuse en raison des proprietes biologiques de la membrane. L’inconvenient principal reste celui d’une prise en charge operatoire en 2 temps. Si la perte de substance depasse 5 cm, l’association d’un segment de fibula multi-perforee et place a l’interieur de la membrane augmente la stabilite primaire et participe a l’integration osseuse. Conclusion Qu’il y ait ou non une perte de substance, la technique de la membrane induite parait appropriee au traitement des pseudarthroses de l’humerus. La strategie en deux interventions reste une mesure de necessite quand on suspecte une infection larvee. Dans le cadre de cette strategie en deux temps, la transposition antero-mediale du nerf radial rend plus aisee la deuxieme intervention de greffe osseuse. Niveau de preuve IV, serie retrospective.

International audience; CC17 Streptococcus agalactiae carrying group-A prophages is increasingly responsible for neonatal infections. To investigate the impact of the genetic features of a group-A prophage, we first conducted an in silico analysis of the genome of 12/111phiA, a group-A prophage carried by a strain responsible for a bloodstream infection in a parturient. This revealed a Restriction Modification system, suggesting a prophage maintenance strategy and five ORFs of interest for the host and encoding a type II toxin antitoxin system RelB/YafQ, an endonuclease, an S-adenosylmethionine synthetase MetK, and an StrP-like adhesin. Using the WT strain cured from 12/111phiA and constructing deleted mutants for the ORFs of interest, and their complemented mutants, we demonstrated an impact of prophage features on growth characteristics, cell morphology and biofilm formation. Our findings argue in favor of 12/111phiA domestication by the host and a role of prophage features in cell autoaggregation, glycocalyx and biofilm formation. We suggest that lysogeny may promote GBS adaptation to the acid environment of the vagina, consequently colonizing and infecting neonates.

To evaluate the global function of patients treated by arthroscopic shoulder stabilization with or without remplissage at a minimum of 10 years of follow-up.The inclusion criteria were existence of a recurrent anterior shoulder dislocation, with or without a Hill-Sachs lesion. The exclusion criteria were prior shoulder stabilization surgery and patients with a glenoid lesion that had been stabilized using the Latarjet procedure. Included patients with a Hill-Sachs lesion underwent surgical remplissage, and the others had Bankart repair only. The main criterion for failure was recurrence of instability or apprehension. The Rowe score and the Walch-Duplay score were used to assess shoulder function before surgery and 10 years afterward, in clinical reviews or telephone interviews.Seventy-nine patients underwent surgical Bankart repair with or without remplissage between November 2004 and January 2008 and were followed up for a mean duration of 128 months (range, 120-150); 12 patients were lost to follow-up, and 39 patients had Bankart stabilization only: the mean Instability Severity Index Score was 2.3 (range, 0-6). Three patients had recurrence with new dislocation, and 8 patients had apprehension. The Rowe score progressed from 54.3 (range, 25-65) to 83.8 (range, 70-100; P.01), and the Walch-Duplay score rose from 46.8 (range, 25-75) to 85.6 (range 70-100; P.01). Twenty-eight patients had arthroscopic Bankart repair + remplissage; the mean Instability Severity Index Score was 1.8 (range, 1-4). There was no recurrence, and no patient had apprehension. The Rowe score progressed from 51.8 (range, 20-65) to 92.3 (range, 70-100; P .01), and the Walch-Duplay score rose from 58.7 (range, 30-75) to 91.4 (range, 70-100; P.01). Functional scores in the second group were statistically significant better than in the first one.Bankart repair combined with remplissage seems to be an effective method for restoring joint stability in patients with recurrent anterior shoulder dislocation with an associated Hill-Sachs lesion at a minimum of 10 years of follow-up. This technique appears to deliver better functional results than Bankart repair only, showing better scores for mobility and stability in the remplissage group. Limitations (pain and restriction of motion) reported in literature at short-term follow-up for this technical procedure do not seem to be anymore an issue at long-term follow-up.Level III, retrospective comparative study.

Central nervous system infections are amongst the most severe1,2, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganismListeria monocytogenes (Lm)is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections3,4. While immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known regarding the bacterial factors underlyingLmneuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6inoculated in a humanized mouse model of infection7, and we show that the bacterial protein InlB protects infected monocytes from CD8+T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lmspecific cellular immune response lengthens infected monocytes lifespan, favoringLmtransfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotesLmfecal shedding, accounting for its selection as aLmcore virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotesLmwithin-host persistence and dissemination to the central nervous system, and transmission.

International audience; IntroductionLe traitement des pseudarthroses humérales avec ou sans perte de substance osseuse est complexe et comporte un taux de complications et d’échecs non négligeables. Rares sont les séries qui s’attardent sur la prise en charge des échecs de cure de pseudarthrose humérale.ObjectifL’hypothèse de ce travail est que l’utilisation de la membrane induite associée à une ostéosynthèse interne avec deux temps opératoires permet d’obtenir une consolidation de manière constante dans le traitement des pseudarthroses rebelles de l’humérus.Matériel et méthodesL’étude portait sur 15 patients, d’âge médian 46,6 ans. En moyenne, les patients présentaient une pseudarthrose humérale depuis 24 mois et avaient déjà été opérés à 3 reprises pour cure de pseudarthrose. Il existait une perte de substance chez 7 patients, elle dépassait 5 cm dans 2 cas. Six patients avaient déjà eu une paralysie radiale.RésultatsLa consolidation a été obtenue chez tous les patients. La durée moyenne de consolidation était de 4,6 mois. Dix patients ont eu une transposition du nerf radial, 6 parmi eux ont présenté une paralysie radiale motrice après la transposition. Ils ont tous récupéré entre 2 et 5 mois. Un cas d’infection superficielle et 1 sérome ont été relevés.DiscussionLa technique de la membrane induite permet d’obtenir une consolidation osseuse en raison des propriétés biologiques de la membrane. L’inconvénient principal reste celui d’une prise en charge opératoire en 2 temps. Si la perte de substance dépasse 5 cm, l’association d’un segment de fibula multi-perforée et placé à l’intérieur de la membrane augmente la stabilité primaire et participe à l’intégration osseuse.ConclusionQu’il y ait ou non une perte de substance, la technique de la membrane induite paraît appropriée au traitement des pseudarthroses de l’humérus. La stratégie en deux interventions reste une mesure de nécessité quand on suspecte une infection larvée. Dans le cadre de cette stratégie en deux temps, la transposition antéro-médiale du nerf radial rend plus aisée la deuxième intervention de greffe osseuse.Niveau de preuveIV, série rétrospective.

Radial nerve palsy is a classical complication of a humeral shaft fracture. In clinical practice, motor palsy of the radial nerve is sometimes observed without an abnormality felt in the sensory territory.We hypothesised that this dissociation between sensory and motor involvement is related to anatomical variations of the sensory innervation of the dorsal surface of the first digit space, thus, we decided to study the nature and frequency of these variations.A cadaveric study was conducted on 24 upper limbs to analyse the truncal origin of the sensory branches innervating the dorsal surface of the first digit space.The sensory branch of the radial nerve (SBRN) participated in the innervation of the dorsal surface of the first digit space in 22 limbs, an anatomical variation was present in 2 cases with a mixed innervation by the SBRN and the lateral cutaneous nerve of forearm (LCNF) in 1 case and singular innervation by LCNF, with no SBRN involvement, in 1 case. Communications between SBRN and LCNF were found in 7 cases.Pure motor radial damage, without a sensory deficit of the dorsal surface of the first digit space, does not preclude a complete traumatic injury of the radial nerve. The sensory innervation of this region can be relayed by a branch of the LCNF.IV; cadaveric study.

Regional anesthesia (RA) is an anesthetic technique essential for the performance of ambulatory surgery. Failure rates range from 6% to 20%, and the consequences of these failures have been poorly investigated. We determined the incidence and the impact of regional block failure on patient management in the ambulatory setting. This retrospective cohort study includes all adult patients who were admitted to a French University Hospital (H&ocirc, pital Saint-Antoine, AP-HP) between 1 January 2016 and 31 December 2017 for unplanned ambulatory distal upper limb surgery. Univariate and stepwise multivariate analyses were performed to determine factors associated with block failure. Among the 562 patients included, 48 (8.5%) had a block failure. RA failure was associated with a longer surgery duration (p = 0.02), more frequent intraoperative analgesics administration (p &lt, 0.01), increased incidence of unplanned hospitalizations (p &lt, 0.001), and a 39% prolongation of Post-Anesthesia Care Unit (PACU) length of stay (p &lt, 0.0001). In the multivariate analysis, the risk factors associated with block failure were female sex (p = 0.04), an American Society of Anesthesiologists (ASA) score &gt, 2 (p = 0.03), history of substance abuse (p = 0.01), and performance of the surgery outside of the specific ambulatory surgical unit (p = 0.01). Here, we have documented a significant incidence of block failure in ambulatory hand surgery, with impairment in the organization of care. Identifying patients at risk of failure could help improve their management, especially by focusing on providing care in a dedicated ambulatory circuit.

The disadvantage of ORIF of proximal humerus fracture (PHF) by intrafocal distraction is that once the device is inserted, it cannot be removed. This study was designed to evaluate the tolerance of such a titanium alloy device at five years of minimal follow-up (FU) and secondarily to assess the relevance of the osteosynthesis of these fractures. Thirty-two patients operated for PHF and implanted with a titanium alloy device between 2009 and 2011 were reviewed: fifteen three-part fracture (3-PF) with mean age 65.2 ± seven years and mean FU at 86 months, and seventeen four-part (4-PF) with mean age 62.9 ± 12 years and mean FU at 88 months. There were no signs of clinical or radiological incompatibility to the metal. The lateral cortex of the humeral shaft at the wedge component level of the device was thinner than pre-operatively in half of the cases. For the fifteen 3-PF, the median raw and weighted constant score (CS) were 75 and 100, respectively. Only one case presented avascular necrosis (AVN). For the seventeen 4-PF, the median raw and weighted CS were 64 and 88, respectively. Seven cases presented AVN and none of them seven had initially a dorsomedial metaphyseal extension of the humeral head. Kaplan–Meier survivorship analysis, with 95% confidence interval, was calculated at 89.7% (79.7–100%) survivorship at 7.18 years of follow-up. This study shows no incompatibility of the titanium alloy device, radiological signs of localized stress shielding in half of the cases with no functional impact, excellent clinical and radiological evolution of the 3-PF, and AVN in all 4-PF without dorsomedial metaphyseal extension of the humeral head whereas most of cases without AVN had dorsomedial metaphyseal extension.

Hemiarthroplasty (HA) for proximal humerus fracture (PHF) is associated with tuberosity complications like migration, non-union, and resorption. In order to improve the rate of consolidation of the greater tuberosity (GT), we have developed a hollow humeral head prosthesis in which the whole humeral head is inserted and used as autograft. This study is designed to evaluate the consolidation rate of the GT with this device. Twenty-two patients at mean age of 68 were treated between 2015 and 2017 for four-part fractures, fracture-dislocations, and head-split fractures with HA including the bony humeral head. The humeral prosthesis device comprises a prosthetic cephalic cup in which the detached humeral head is inserted and a cementless adjustable humeral stem which works like a jack. Mean follow-up was 14 months. The consolidation of GT was followed on X-rays. As comparison, 15 published series were selected and analyzed. There were two mechanical complications related to GT consolidation (9.1%). In the 20 other cases, the GT was radiologically consolidated without displacement. While the raw proportion of complications observed in the present series was lower than that reported in each of the 15 comparative series, the proportion of complications observed in the present series was significantly different from that observed only in seven out of the 15 previous series. Whole conservation of the humeral head as an autograft along with proper surgical technique yielded in 20 consolidations of GT without displacement in 22 cases of PHF treated with hemiarthroplasty.

Introduction The unique anatomical characteristics of the forearm bones makes their reconstruction challenging. The aim of this study was to report the surgical methods and results of the induced membrane technique applied to traumatic forearm bone defects. Material and methods We evaluated retrospectively a case series of 13 patients operated between 2010 and 2017. The first surgical step consisted of debridement of the fracture site and implantation of a cement spacer with appropriate fixation. The anatomy of the forearm skeleton had to be restored. The second step, done 6 weeks later, consisted of removing the cement spacer and applying cancellous bone autograft harvested from the iliac crest. The outcome measures were radiological bone union, need for surgical revision, and postoperative wrist range of motion. Results All 13 patients were men, with a mean age of 39 years (18–67). The average follow-up was 2.5 years. Eleven patients were suffering from a nonunion and two from a post-traumatic bone defect. Six patients had an identified preoperative infection. Three patients had previously undergone an unsuccessful treatment for their nonunion with bone addition. The maximum length of bone reconstruction was 12 cm. Union was achieved in 12 of 13 patients in a mean of 5 months (3–8). The other patient died during the postoperative course. Two patients needed revision surgery: ulnar shortening osteotomy (1 case) and additional tendon reconstruction (1 case). The mean pronosupination range was 123° on average (55–180°). The mean flexion-extension range was 106° (90–130°). Conclusion The induced membrane technique is a reliable reconstruction technique that is well suited to reconstruction of the forearm skeleton. Level of evidence IV, retrospective study.

Kimura disease (KD) is a rare inflammatory soft tissue disorder of unknown origin most frequent in Asians, the prevalence of which is growing in Western countries. Painless papules and/or nodules with a predilection for the head and the neck region, lymphadenopathies, parotid gland involvement, eosinophilia, and raised IgE levels are parts of its presentation. Renal involvement with various forms of glomerulonephritis, including membranous nephropathy (MN), can occur and is generally associated with a proteinuria that encompasses nephrotic syndrome. Corticosteroids are the mainstay of treatment of KD-associated glomerulonephritis, but steroids withdrawal is often followed by relapsing nephrotic syndrome. Various immunosuppressive agents have been tested to prolong the remission of KD-associated nephrotic syndrome while tapering steroids, but they are only partly effective or associated with significant complications. To the best of our knowledge, we describe here the first case of KD-related membranous glomerulonephritis with a favorable evolution and a sustained remission of 4 years under prolonged therapy with mycophenolic acid (MPA). MPA and its active metabolite, mycophenolate mofetil (MMF), treatments as supportive therapies to corticosteroids and ACE inhibitors should be further investigated in KD-related membranous nephropathies. .

National audience

Acromioclavicular (AC) joint arthropathy remains one of the most common causes of shoulder pain. In the case of AC joint arthropathy resistant to conservative treatment, most authors have recognized distal clavicle resection as the gold-standard treatment. However, some challenges remain to be solved. One is the difficulty in visualization of the superior and posterior part of the distal clavicle from the midlateral portal, causing an incomplete resection of the distal clavicle. This could potentially lead to unresolved pain and therefore surgical failure. We propose a technique for arthroscopic resection of the distal clavicle and the medial portion of the acromion, without any added portal: bipolar AC joint resection. The term “bipolar” is used because both the acromion and the clavicle are resected, without injuring the superior capsule.

Introduction La technique de remplissage a ete developpee pour traiter les lesions engageantes de la tete humerale. Peu d’etudes comparent les resultats du Bankart arthroscopique a ceux du Bankart avec remplissage. Notre hypothese est que la technique chirurgicale arthroscopique de Bankart associee avec la technique de remplissage pour traiter l’instabilite anterieure avec lesion de Hill-Sachs permet d’obtenir des resultats fonctionnels satisfaisants a 10 ans de recul. Materiel et methode Soixante-dix-neuf patients ont ete operes par technique de Bankart avec ou sans remplissage pour une instabilite recidivante de l’epaule entre novembre 2004 et janvier 2008, et ont ete suivis pendant une duree moyenne de 128 mois (extremes : 120–150). Tous les patients avaient une instabilite anterieure traumatique unidirectionnelle de l’epaule. Les patients avec une lesion de Hill Sachs confirmee en per operatoire ont eu une chirurgie de remplissage, les autres un Bankart isole. Le critere principal d’echec etait la recidive de l’instabilite ou de l’apprehension. Le score de Rowe et le score de Walch Duplay ont ete utilises pour evaluer la fonction de l’epaule avant la chirurgie et dix ans apres. Resultats Douze patients ont ete perdus de vue. Trente-neuf patients ont eu une stabilisation par Bankart seul. Trois patients ont recidive avec nouvel episode de luxation. Chez les patients n’ayant pas recidive, le score de Rowe au augmente de 46,8 a 85,6 (p > 0,01), et le score de Walch de 54,3 a 83,8 (p > 0,0001). Vingt-huit patients ont eu un Bankart arthroscopique avec remplissage. Il n’y avait pas de recidive ni de complication postoperatoire. Le score de Rowe a augmente de 51,8 a 93 (p > 0,0001), et le score de Walch de 58,7 a 91,4 (p > 0,0001). Discussion A 10 ans, les scores de Rowe et Walch sont significativement plus eleves dans le groupe Bankart + remplissage que le groupe Bankart seul. Par ailleurs, le detail du Walch retrouvait des scores plus eleves concernant la mobilite chez les patients operes par Bankart + remplissage avec une difference non significative pour les parametres stabilite et mobilite et douleur. Conclusion La reparation de Bankart associee avec la technique de remplissage semble etre une technique efficace pour restaurer la stabilite articulaire chez les patients avec luxation anterieure recidivante de l’epaule associee a des lesions de Hill-Sachs dans un suivi a 10 ans.

Cet article est une contribution à l’analyse des effets des réseaux sociaux sur la formation des goûts et des opinions en matière culturelle. En prenant l’exemple des usages de Twitter au Festival de Cannes par trente-deux professionnels partenaires de Vodkaster qui jouent ensemble sur la scène can­noise et en s’appuyant principalement sur une analyse lexicale, on peut mettre au jour trois notions structurantes : celle d’outsi­der numérique – la déviance étant constitutive de l’événement –, celle de leadership fondée sur la fidélité du lectorat, et celle d’un quatrième cercle de spectateurs qui construit son expérience du Festival par procuration. Les réseaux sociaux numériques consti­tuent ainsi à la fois une ressource aisément exploitable pour l’ana­lyse des publics et une forme spécifique de la sociabilité festivalière. This article is a contribution to the analysis of the effects of social networks on the shaping of taste and opinions concerning cultural matters. Taking as an example the Twitter usage of thirty-two professional partners of Vodkaster who play with each other on the Cannes stage and using mainly lexical ana­lysis, one can shed light on three structural concepts: the digital outsider – his deviance being a central feature of the event, lea­dership – based on faithful readership, and the fourth circle of spectators who experience the festival by proxy. Thus, digital social networks are both an easily mobilized resource for the analysis of audience and a specific form of festival-goer’s sociability. Este artículo es una contribución al análisis de los efectos de las redes sociales sobre la formación de los gus­tos y de las opiniones en materia cultural. Tomando el ejemplo de los usos de Twitter en el festival de Cannes de treinta y dos profesionales (socios de Vodkaster) que tocan juntos en la escena local, y apoyados fundamentalmente en un análisis lexical, pode­mos dar a luz tres nociones estructurantes : la de outsider numérico (la desviación constitutiva del acontecimiento), la de liderazgo fundada sobre la fidelidad de los lectores y la del cuarto círculo de espectadores que construye su experiencia del festival en su nombre. Las redes sociales constituyen a la vez un recurso fácilmente explotable para el análisis de los públicos y una forma específica de la sociabilidad del festival.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a potentially severe food allergy. Physical exercise, NSAID, alcohol, infectious diseases and estrogens are recognized cofactors, able to reduce the amount of allergen needed to achieve a threshold for the induction of anaphylaxis. Various kinds of causative food but only a few responsible proteins have been identified. The best known is wheat ω5-gliadine. An oral food challenge remains the gold standard to prove the diagnosis. Its clinical application remains difficult and includes an allergen challenge, a cofactor challenge and a third step which integrates both of them in a single test. Gluten flour and NSAID + alcohol combination seem more efficient than respectively wheat flour and physical exercise in a provocation test condition.L’anaphylaxie alimentaire à l’effort est une allergie alimentaire potentiellement sévère. L’exercice physique, les AINS, l’alcool, les infections et les œstrogènes sont des cofacteurs reconnus, capables de diminuer la quantité d’allergènes nécessaire à l’atteinte d’un seuil anaphylactique. Si le panel d’aliments incriminés est large, seules quelques protéines responsables ont été à ce jour identifiées. La plus connue est l’ω5-gliadine du blé. En cas d’incertitude diagnostique, un test de provocation est indiqué. Son application clinique reste difficile et inclut de tester l’allergène de manière isolée et le cofacteur puis d’intégrer les deux dans un même test. La farine de gluten et la combinaison AINS + alcool ont une sensibilité supérieure respectivement à la farine de blé et à l’exercice physique en situation de provocation.

Soft tissue defect on lower limb can result in an intractable wound. Surgeons resort in flaps to cover these injuries. Including fascia as in the case of a fasciocutaneous flap increases survey of the flap. Rising a perforator flap avoids to sacrifice a major vessel whence the nourishing perforator artery is born. We wanted to explore suprafascial distribution of the fibular skin perforator arteries supposing possible to find out a vascular axis composed of anastomoses of the fibular perforator vessels. Systematic observation was carried out on ten injected legs about the fibular perforator distribution, and especially their suprafascial course. Dissection allowed us to raise in all specimens a large fasciocutaneous paddle including a fine arteriolar vessel connecting fibular perforators. Perforators were isolated along from the leg and we found suprafascial arteriole connecting all perforators from the fibular head to the lateral malleolus. There were a total number of 126 perforators for 10 legs. The mean length of the fibula was 32.9 cm. No perforator was located at more than 2 cm from fibular posterior border. Proximal perforators were closer to posterior fibular side than distal perforators. We found that fibular perforators clustered in the middle and upper third of the leg. This study proves the real existence of a microvascular suprafascial axis formed by fibular perforator anastomoses and stretching over the entire length of the fibula, from the fibular head to the distal tip of the lateral malleolus. This suprafascial vascular axis could be an anatomical basis for a fasciocutaneous fibular flap.

Bone-marrow mesenchymal stem cells (MSCs) are the origin of bone-forming cells with immunomodulation potential. HLA-G5 is among the generated immunosuppressive molecules. HLA-G proteins play a crucial role in promoting the acceptance of allografts. However, the mechanisms regulating the expression of HLA-G5 in human MSCs are unknown. We induced differentiation of MSCs and found that HLA-G5 was greatly up-regulated only in osteoblastic cells (+63% for mRNA). Growth plates and bone callus postfracture in adults showed that only bone-lining cells and mesenchymal progenitors were positive for HLA-G5. Use of gene silencing and dominant-negative factors revealed that HLA-G5 depends on the expression and function of the skeletogenesis master genes RUNX2 and DLX5. In addition, HLA-G5 could directly inhibit osteoclastogenesis by acting on monocytes through SHP1. However, in mature osteoblasts, the expression of HLA-G5 protein was greatly suppressed whereas the proosteoclastogenic factor, RANKL, was concomitantly increased. Down-regulation of HLA-G5 expression during the maturation of osteoblasts was due to binding of the repressor GLI3, a signal transducer of the Hedgehog pathway, to the GLI binding element within the HLA-G promoter. Our findings show that mesenchymal progenitors and osteoblastic cells specifically express HLA-G5 during osteogenesis, with a key role in bone homeostasis.

International audience; The main features of lung infection and inflammation are a massive recruitment of neutrophils and the subsequent release of neutrophil serine proteases (NSPs). Anti-infectious and/or anti-inflammatory treatments must be tested on a suitable animal model. Mice models do not replicate several aspects of human lung disease. This is particularly true for cystic fibrosis (CF), which has led the scientific community to a search for new animal models. We have shown that mice are not appropriate for characterizing drugs targeting neutrophil-dependent inflammation and that pig neutrophils and their NSPs are similar to their human homologues. We induced acute neutrophilic inflammatory responses in pig lungs using Pseudomonas aeruginosa, an opportunistic respiratory pathogen. Blood samples, nasal swabs and bronchoalveolar lavage fluids (BALFs) were collected at 0, 3, 6 and 24 h post-insfection (p.i.) and biochemical parameters, serum and BAL cytokines, bacterial cultures and neutrophil activity were evaluated. The release of proinflammatory mediators, biochemical and hematological blood parameters, cell recruitment and bronchial reactivity, peaked at 6h p.i.. We also used synthetic substrates specific for human neutrophil proteases to show that the activity of pig NSPs in BALFs increased. These proteases were also detected at the surface of lung neutrophils using anti-human NSP antibodies. Pseudomonas aeruginosa-induced lung infection in pigs results in a neutrophilic response similar to that described for cystic fibrosis and ventilator-associated pneumonia in humans. Altogether, this indicates that the pig is an appropriate model for testing anti-infectious and/or anti-inflammatory drugs to combat adverse proteolytic effects of neutrophil in human lung diseases.

Objective HCV particles are associated with very low-density lipoprotein components in chronically infected patients. These hybrid particles, or ‘lipo-viro particles’ (LVPs), are rich in triglycerides, and contain the viral RNA, the capsid protein, E1E2 envelope glycoproteins and apolipoproteins B and E. However, their specific ultrastructural organisation has yet to be determined. We developed a strategy for the preparation of any viral sample that preserves the native structure of the LVPs, facilitating their precise morphological characterisation. Design Using a strategy based on the direct specific immunocapture of particles on transmission electron microscopy (TEM) grids, we characterised the precise morphology of the viral particle by TEM. Results The LVP consists of a broad nucleocapsid surrounding an electron-dense centre, presumably containing the HCV genome. The nucleocapsid is surrounded by an irregular, detergent-sensitive crescent probably composed of lipids. Lipid content may determine particle size. These particles carry HCV E1E2, ApoB and ApoE, as shown in our immuno-EM analysis. Our results also suggest that these putative LVPs circulate in the serum of patients as part of a mixed population, including lipoprotein-like particles and complete viral particles. Conclusions Twenty-five years after the discovery of HCV, this study finally provides information about the precise morphological organisation of viral particles. It is truly remarkable that our TEM images fully confirm the ultrastructure of LVPs predicted by several authors, almost exclusively from the results of molecular biology studies.

International audience; Traumatic trapeziometacarpal joint dislocation of the thumb accounts for less than 1% of all hand injuries. This injury is even less common in children. Optimal treatment strategies for this injury are still the subject of debate for both children and adults. We report a case of recurrent posttraumatic trapeziometacarpal joint dislocation in an eight-year-old girl. We believe our case is the first report of recurrent acute dislocation leading to chronic dislocation in the English medical literature. Restoring the anatomy and biomechanics of the trapeziometacarpal joint is essential when treating these injuries; for this reason, surgical treatment is usually indicated. Overall, the prognosis of trapeziometacarpal dislocation treated acutely is favorable and stable over time. However, the role of open surgery and ligament reconstruction remains controversial, especially in children.; La luxation de l’articulation trapézo-métacarpienne compte pour moins de 1 % des traumatismes de la main. Cette lésion est encore plus rarement observée chez les enfants. Le traitement optimal de ce traumatisme reste controversé chez l’enfant, comme chez l’adulte. Cet article rapporte le cas d’une luxation récidivante de l’articulation trapézo-métacarpienne chez une enfant de 9 ans. Au regard de la littérature, il semblerait que cela soit le premier cas de luxation récidivante, conduisant à une instabilité chronique. Restaurer l’anatomie et la biomécanique de l’articulation trapézo-métacarpienne est essentiel lors de la prise en charge de ces traumatismes, et c’est la raison pour laquelle le traitement chirurgical est indiqué. Les luxations trapézo-métacarpiennes prises en charge précocement sont généralement de bon pronostic, avec une évolution stable au fil du temps. Le rôle de la ligamentoplastie reste controversé, particulièrement chez l’enfant.

Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.

International audience; Hepatitis C virus (HCV) assembly is still poorly understood. It is thought that trafficking of the HCV core protein to the lipid droplet (LD) surface is essential for its multimerization and associ- ation with newly synthesized HCV RNA to form the viral nucleocapsid. We carried out a mapping analysis of several complete HCV genomes of all genotypes, and found that the genotype 2 JFH-1 core protein contained 10 residues different from those of other genotypes. The replacement of these 10 residues of the JFH-1 strain sequence with the most conserved residues deduced from sequence alignments greatly increased virus production. Confocal microscopy of the modified JFH-1 strain in cell culture showed that the mutated JFH-1 core protein, C10M, was present mostly at the endoplasmic reticulum (ER) membrane, but not at the surface of the LDs, even though its trafficking to these organelles was possible. The non- structural 5A protein of HCV was also redirected to ER membranes and colocalized with the C10M core protein. Using a Semliki forest virus vector to overproduce core protein, we demon- strated that the C10M core protein was able to form HCV-like particles, unlike the native JFH-1 core protein. Thus, the substitution of a few selected residues in the JFH-1 core protein modi- fied the subcellular distribution and assembly properties of the protein. These findings suggest that the early steps of HCV assembly occur at the ER membrane rather than at the LD surface. The C10M-JFH-1 strain will be a valuable tool for further studies of HCV morphogenesis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective death of motor neurons. Mutations in the SOD1 gene encoding the superoxide dismutase 1 are present in 15% of familial ALS cases and in 2% of sporadic cases. These mutations are associated with the formation of SOD1-positive aggregates. The mechanisms of aggregation remain unknown, but posttranslational modifications of SOD1 may be involved. Here, we report that NSC-34 motor neuronal cells expressing mutant SOD1 contained aggregates positive for small ubiquitin modifier-1 (SUMO-1), and in parallel a reduced level of free SUMO-1. CLEM (correlative light and electron microscopy) analysis showed nonorganized cytosolic aggregates for all mutations tested (SOD1A4V, SOD1V31A, and SOD1G93C). We next show that preventing the SUMOylation of mutant SOD1 by the substitution of lysine 75, the SUMOylation site of SOD1, significantly reduces the number of motor neuronal cells with aggregates. These results support the need for further research on the SUMOylation pathways, which may be a potential therapeutic target in ALS.

Real-world Recommender Systems are often facing drifts in users’ preferences and shifts in items’ perception or use. Traditional state-of-the-art methods based on matrix factorization are not originally designed to cope with these dynamic and time-varying effects and, indeed, could perform rather poorly if there is no ”reactive”, on-line model update. In this paper, we propose a new incremental matrix completion method, that automatically allows the factors related to both users and items to adapt “on-line” to such drifts. Model updates are based on a temporal regularization, ensuring smoothness and consistency over time, while leading to very efficient, easily scalable algebraic computations. Several experiments on real-world data sets show that these adaptation mechanisms significantly improve the quality of recommendations compared to the static setting and other standard on-line adaptive algorithms.

A large double-stranded DNA (dsDNA) virus that produces occlusion bodies, typical of baculoviruses, has been described to infect crane fly larvae of the genus Tipula (Diptera, Tipulidae). Because of a lack of genomic data, this virus has remained unclassified. Electron microscopy of an archival virus isolated from Tipula oleracea , T. oleracea nudivirus (ToNV), showed irregularly shaped occlusion bodies measuring from 2 to 5 μm in length and 2 μm in middiameter, filled with rod-shape virions containing single nucleocapsids within a bilayer envelope. Whole-genome amplification and Roche 454 sequencing revealed a complete circular genome sequence of 145.7 kb, containing five direct repeat regions. We predicted 131 open reading frames, including a homolog of the polyhedrin gene encoding the major occlusion body protein of T. paludosa nucleopolyhedrovirus (NPV). BLAST searches demonstrated that ToNV had 21 of the 37 baculovirus core genes but shared 52 genes with nudiviruses (NVs). Phylogenomic analyses indicated that ToNV clearly belongs to the Nudiviridae family but should probably be assigned to a new genus. Among nudiviruses, ToNV was most closely related to the Penaeus monodon NV and Heliothis zea NV clade but distantly related to Drosophila innubia NV, the other nudivirus infecting a Diptera. Lastly, ToNV was found to be most closely related to the nuvidirus ancestor of bracoviruses. This was also reflected in terms of gene content, as ToNV was the only known exogenous virus harboring homologs of the Cc50C22.6 and 27b ( Cc50C22.7 ) genes found in the nudiviral genomic cluster involved in bracovirus particle production. IMPORTANCE The Nudiviridae is a family of arthropod dsDNA viruses from which striking cases of endogenization have been reported (i.e., symbiotic bracoviruses deriving from a nudivirus and the endogenous nudivirus of the brown planthopper). Although related to baculoviruses, relatively little is known about the genomic diversity of exogenous nudiviruses. Here, we characterized, morphologically and genetically, an archival sample of the Tipula oleracea nudivirus (ToNV), which has the particularity of forming occlusion bodies. Comparative genomic and phylogenomic analyses showed ToNV to be to date the closest known relative of the exogenous ancestor of bracoviruses and that ToNV should be assigned to a new genus. Moreover, we revised the homology relationships of nudiviral genes and identified a new set of 32 core genes for the Nudiviridae , of which 21 were also baculovirus core genes. These findings provide important insights into the evolutionary history of large arthropod dsDNA viruses.

Background Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. Results In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. Conclusions The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses. Electronic supplementary material The online version of this article (doi:10.1186/s12977-014-0103-y) contains supplementary material, which is available to authorized users.

L’afflux massif de refugies et de migrants appelle une reponse urgente a leurs besoins sanitaires. Celle-ci est assuree par les Permanences d’acces aux soins de sante medico-sociales (PASS), pour des patients vulnerables. Ces lieux d’accueil, d’information, de prevention, d’orientation et de soins sociaux et medicaux sont un modele de pratique ouvrant des perspectives a l’ensemble du systeme de sante francais.

BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-blind phase Ib clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens, with a New York vaccinia HIV clade B (NYVAC-B) vaccine and a recombinant adenovirus 5–vectored (rAd5-vectored) vaccine. METHODS. NYVAC-B included HIV-1 clade B Gag-Pol-Nef and gp120, while rAd5 included HIV-1 clade B Gag-Pol and clades A, B, and C gp140. Eighty Ad5-seronegative subjects were randomized to receive 2 × NYVAC-B followed by 1 × 1010 PFU rAd5 (NYVAC/Ad5hi); 1 × 108 PFU rAd5 followed by 2 × NYVAC-B (Ad5lo/NYVAC); 1 × 109 PFU rAd5 followed by 2 × NYVAC-B (Ad5med/NYVAC); 1 × 1010 PFU rAd5 followed by 2 × NYVAC-B (Ad5hi/NYVAC); or placebo. Immune responses were assessed 2 weeks after the final vaccination. Intracellular cytokine staining measured T cells producing IFN-γ and/or IL-2; cross-clade and epitope-specific binding antibodies were determined; and neutralizing antibodies (nAbs) were assessed with 6 tier 1 viruses. RESULTS. CD4+ T cell response rates ranged from 42.9% to 93.3%. NYVAC/Ad5hi response rates (P ≤ 0.01) and magnitudes (P ≤ 0.03) were significantly lower than those of other groups. CD8+ T cell response rates ranged from 65.5% to 85.7%. NYVAC/Ad5hi magnitudes were significantly lower than those of other groups (P ≤ 0.04). IgG response rates to the group M consensus gp140 were 89.7% for NYVAC/Ad5hi and 21.4%, 84.6%, and 100% for Ad5lo/NYVAC, Ad5med/NYVAC, and Ad5hi/NYVAC, respectively, and were similar for other vaccine proteins. Overall nAb responses were low, but aggregate responses appeared stronger for Ad5med/NYVAC and Ad5hi/NYVAC than for NYVAC/Ad5hi. CONCLUSIONS. rAd5 prime followed by NYVAC boost is superior to the reverse regimen for both vaccine-induced cellular and humoral immune responses. Higher Ad5 priming doses significantly increased binding and nAbs. These data provide a basis for optimizing the design of future clinical trials testing vector-based heterologous prime-boost strategies. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00961883","term_id":"NCT00961883"}}NCT00961883. FUNDING. NIAID, NIH UM1AI068618, {"type":"entrez-nucleotide","attrs":{"text":"AI068635","term_id":"3391610","term_text":"AI068635"}}AI068635, {"type":"entrez-nucleotide","attrs":{"text":"AI068614","term_id":"3391589","term_text":"AI068614"}}AI068614, and {"type":"entrez-nucleotide","attrs":{"text":"AI069443","term_id":"3392418","term_text":"AI069443"}}AI069443.