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The present study explores the frequency, diagnostic approach, and therapeutic management of cerebral vasospasm in a cohort of children with moderate-to-severe traumatic and nontraumatic subarachnoid hemorrhage (SAH). This was a single-center retrospective study performed over a 10-year period, from January 2010 to December 2019. Children aged from one month to 18 years who were admitted to the pediatric or adult intensive care unit with a diagnosis of SAH were eligible. Cerebral vasospasm could be suspected by clinical signs or transcranial Doppler (TCD) criteria (mean blood flow velocity > 120 cm/s or an increase in mean blood flow velocity by > 50 cm/s within 24 h) and then confirmed on cerebral imaging (with a reduction to less than 50% of the caliber of the cerebral artery). Eighty patients aged 8.6 years (3.3–14.8 years, 25–75th centiles) were admitted with an initial Glasgow Coma Scale score of 8 (4–12). SAH was nontraumatic in 21 (26%) patients. A total of 14/80 patients (18%) developed cerebral vasospasm on brain imaging on day 6 (5–10) after admission, with a predominance of nontraumatic SAH (12/14). The diagnosis of cerebral vasospasm was suspected on clinical signs and/or significant temporal changes in TCD monitoring (7 patients) and then confirmed on cerebral imaging. Thirteen of 14 patients with vasospasm were successfully treated using a continuous intravenous infusion of milrinone. The Pediatric Cerebral Performance Category score at discharge from the intensive care unit was comparable between children with vasospasm (score of 2 [1–4]) vs. children without vasospasm (score of 4 [2–4]) (p = 0.09). These findings indicate that cerebral vasospasm exists in pediatrics, particularly after nontraumatic SAH. The use of TCD and milrinone may help in the diagnostic and therapeutic management of cerebral vasospasm.

Many applications of transcranial Doppler (TCD) as a diagnosis or monitoring tool have raised interest in the last decades. It is important that clinicians know when and how to perform TCD in this population, what parameter to assess and monitor and how to interpret it. This review aims to describe the emerging clinical applications of TCD in critically ill children excluding those suffering from trauma. Databases Web of Science, Cochrane and PubMed were searched in May 2020. We considered all publications since the year 2000 addressing the use of TCD as a prognostic, diagnostic or follow-up tool in children aged 0 to 15 years admitted to intensive care or emergency units, excluding neonatology and traumatic brain injury. Two independent reviewers selected 82 abstracts and full-text articles from the 2011 unique citations identified at the outset. TCD provides crucial additional information at bedside about cerebrovascular hemodynamics. Many clinical applications include the diagnosis and management of various medical and surgical neurologic conditions (central nervous system infections, arterial ischemic stroke, subarachnoid hemorrhage and vasospasm, brain death, seizures, metabolic disease, hydrocephalus) as well as monitoring the impact systemic conditions on brain perfusion (hemodynamic instability, circulatory assistance). To conclude, TCD has become an invaluable asset for non-invasive neuromonitoring in critically ill children excluding those suffering from trauma. However, the scope of TCD remains unclearly defined yet and reference values in critically ill children are still lacking.

This study aimed to assess how the emergence of high-flow nasal cannula (HFNC) has modified the demographic and clinical characteristics as well as outcomes of infants with bronchiolitis admitted to a pediatric intensive care unit (PICU).This was a single-center retrospective study including infants aged 1 day to 6 months with bronchiolitis requiring HFNC, noninvasive ventilation (NIV), or invasive ventilation on admission.A total of 252 infants (mean age 53±36 days) were included in the study. The use of HFNC increased from 18 (21.4%) during 2013-2014 to 53 infants (55.2%) during 2015-2016. The length of stay in the PICU decreased over time from 4.7±2.9 to 3.5±2.7 days (P0.01) but the hospital length of stay remained similar (P=0.17). On admission, patients supported by HFNC as the first-line therapy were older. The PICU length of stay was similar according to the type of respiratory support (P=0.16), but the hospital length of stay was longer for patients supported by HFNC (P=0.01).The distribution of respiratory support has significantly changed over time for patients with bronchiolitis and HFNC is increasingly used. The demographic and clinical characteristics of the have not changed over time. However, the PICU length of stay decreased significantly.

Abusive Head Trauma (AHT) remains the leading cause of brain injury in infants.This study aims to describe a cohort of patients with AHT and identify early risk factors associated with poor neurological outcome.Children under one year old admitted to a Pediatric Intensive Care Unit (PICU) with a suspected or confirmed diagnosis of AHT were included. Neurological outcome was assessed by the Pediatric Overall Performance Category score (POPC) at discharge from the hospital and at two years of follow-up.A multicentre retrospective study was conducted over 8 years (from January 2012 to December 2020).A total of 117 patients (mean age 4.3 (+/- 2.5) months, 61 % boys) from three PICUs were included. A total of 99 (85 %) patients completed a 2-year follow-up. Sixty-one (52 %) and 47 (40 %) children with AHT had a POPC (pediatric overall performance category) score ≥ 2 at discharge from ICU and discharge from hospital, respectively (meaning they had at least a moderate disability). Fifty-one (44 %) had a POPC score ≥ 2 at 2-year follow-up, including 19 patients (19 %) with severe disabilities. The main neurological disabilities were neurodevelopmental (n = 38, 35 %), hyperactivity disorder (n = 36, 33 %) and epilepsy (n = 34, 31 %). After analysis according to the hierarchical model, the occurrence of a cardiorespiratory arrest and a low Glasgow Coma Score at admission stand out as factors of poor neurological outcome.This study highlights the wide range of neurological disabilities in children with AHT. Early and multidisciplinary follow-up is crucial to limit the impact of neurological disability.

Background Malignant pertussis (MP) affects young infants and is characterized by respiratory distress, perpetual tachycardia and hyperleukocytosis up to 50 G/l, leading to multiple organ failure and death in 75% of cases. Leukodepletion may improve prognosis. A therapeutic strategy based on leukodepletion and extracorporeal life support (ECLS) according to different thresholds of leucocytes has been proposed by Rowlands and colleagues. We aimed at identifying factors associated with death and assess whether the respect of the Rowlands’ strategy is associated with survival. Methods We reviewed all MP infants hospitalized in eight French pediatric intensive care units from January 2008 to November 2013. All infants younger than 3 months of age, admitted for respiratory distress with a diagnosis of pertussis and WBC count ≥ 50 G/l were recorded. Evolution of WBC was analyzed and an optimal threshold for WBC growth was obtained using the ROC-curve method. Clinical and biological characteristics of survivors and non-survivors were compared. Therapeutic management (leukodepletion and/or ECLS) was retrospectively assessed for compliance with Rowlands’ algorithm (indication and timing of specific treatments). Results Twenty-three infants were included. Nine of 23 (40%) died: they presented more frequently cardiovascular failure (100% vs 36%, p = 0.003) and pulmonary hypertension (PHT; 100% vs 29%, p = 0.002) than survivors and the median [IQR] WBC growth was significantly faster among them (21.3 [9.7–28] G/l/day vs 5.9 [3.0–6.8] G/l/day, p = 0.007). WBC growth rate > 12 G/l/day and lymphocyte/neutrophil ratio p = 0.001 and p = 0.003, respectively). Ten infants (43%) underwent leukodepletion, and seven (30%) underwent ECLS. Management following Rowlands’ strategy was associated with survival (100% vs 0%; p Conclusions A fast leukocyte growth and leukocytosis with neutrophil predominance during acute pertussis infection were associated with death. These findings should prompt clinicians to closely monitor white blood cells in order to early identify infants at risk of fatal outcome during the course of malignant pertussis. Such an early signal in infants at high risk of death would increase feasibility of compliant care to Rowlands’ strategy, with the expectation of a better survival.

The present study explores the frequency, diagnostic approach, and therapeutic management of cerebral vasospasm in a cohort of children with moderate-to-severe traumatic and nontraumatic subarachnoid hemorrhage (SAH).This was a single-center retrospective study performed over a 10-year period, from January 2010 to December 2019. Children aged from one month to 18 years who were admitted to the pediatric or adult intensive care unit with a diagnosis of SAH were eligible. Cerebral vasospasm could be suspected by clinical signs or transcranial Doppler (TCD) criteria (mean blood flow velocity 120 cm/s or an increase in mean blood flow velocity by 50 cm/s within 24 h) and then confirmed on cerebral imaging (with a reduction to less than 50% of the caliber of the cerebral artery).Eighty patients aged 8.6 years (3.3-14.8 years, 25-75th centiles) were admitted with an initial Glasgow Coma Scale score of 8 (4-12). SAH was nontraumatic in 21 (26%) patients. A total of 14/80 patients (18%) developed cerebral vasospasm on brain imaging on day 6 (5-10) after admission, with a predominance of nontraumatic SAH (12/14). The diagnosis of cerebral vasospasm was suspected on clinical signs and/or significant temporal changes in TCD monitoring (7 patients) and then confirmed on cerebral imaging. Thirteen of 14 patients with vasospasm were successfully treated using a continuous intravenous infusion of milrinone. The Pediatric Cerebral Performance Category score at discharge from the intensive care unit was comparable between children with vasospasm (score of 2 [1-4]) vs. children without vasospasm (score of 4 [2-4]) (p = 0.09).These findings indicate that cerebral vasospasm exists in pediatrics, particularly after nontraumatic SAH. The use of TCD and milrinone may help in the diagnostic and therapeutic management of cerebral vasospasm.

Background Little is known about the effect of under triage on early mortality in trauma in a pediatric population. Our objective is to describe the effect of under triage on 24-h mortality after major pediatric trauma in a regional trauma system. Methods This cohort study was conducted from January 2009 to December 2017. Data were obtained from the registry of the Northern French Alps Trauma System. The network guidelines triage pediatric trauma patients according to an algorithm shared with adult patients. Under triage was defined by the number of pediatric trauma patients that required specialized trauma care transported to a non-level I pediatric trauma center on the total number of injured patients with critical resource use. The effect of under triage on 24-h mortality was assessed with inverse probability treatment weighting (IPTW) and a propensity score (Ps) matching analysis. Results A total of 1143 pediatric patients were included (mean [SD], age 10 [5] years), mainly after a blunt trauma (1130 [99%]). Of the children, 402 (35%) had an ISS higher than 15 and 547 (48%) required specialized trauma care. Nineteen (1.7%) patients died within 24 h. Under triage rate was 33% based on the need of specialized trauma care. Under triage of children requiring specialized trauma care increased the risk of death in IPTW (risk difference 6.0 [95% CI 1.3–10.7]) and Ps matching analyses (risk difference 3.1 [95% CI 0.8–5.4]). Conclusions In a regional inclusive trauma system, under triage increased the risk of early death after pediatric major trauma.

Rational This study aims at describing the use of bilevel positive airway pressure (BiPAP) in infants with severe bronchiolitis. Working hypothesis The use of BiPAP in infants with bronchiolitis may be associated with a worst outcome. Study design A single-center retrospective study performed from October 2013 to April 2016. Methodology All infants from 1 day to 6 months of age admitted in the pediatric intensive care unit (PICU) were included if they had a clinical diagnosis of bronchiolitis and if they required any type of noninvasive ventilation (NIV), including high flow nasal cannula, continuous positive airway pressure and BiPAP at admission in PICU. There was no local written protocol regarding the ventilator management during the study. Results Overall, 252 infants (median age 45 (26-72) days) were included in the study and 110 infants (44%) were supported by BiPAP at admission. More infants were born preterm in the group of patients supported by BiPAP at admission. No complication related to NIV occurred. Patients in the BiPAP group had a longer duration of noninvasive support as well as a longer PICU length of stay. However, hospital length of stay did not differ according to the type of respiratory support at admission. Conclusion The use of BiPAP was not associated with endotracheal intubation, however it was associated with increased PICU length of stay and increased duration of NIV.

Acute epiglottis is a life-threatening disease in relation with the occurrence of an acute upper airway obstruction. Its incidence has fallen dramatically since the widespread introduction of Haemophilus influenzae type b (Hib) conjugate vaccine. We report the case of a 26-month-old child who was not fully immunized and presented acute upper airway respiratory distress with fever. The symptoms quickly evolved to a respiratory arrest condition with bradycardia, revealing epiglottitis due to Hib. Despite high immunization coverage with great efficacy and occurrence of herd immunity, this entity still exists because of the French population's skepticism of the routine vaccination schedule.

Objectives Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Design Experimental study. Setting Neurosciences and physiology laboratories. Subjects Adult male Wistar rats. Interventions Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Measurements and main results Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. Conclusion The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.

Background The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Methods Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI–saline group) or HSL (TBI–HSL group). The sham–saline and sham–HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy ( n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach ( n = 10 rats per group), and 3) mitochondrial ultrastructural changes ( n = 1 rat per group). Results Compared with the TBI–saline group, the TBI–HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI–HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047–0.098) vs 0.097 (0.079–0.157); P vs 66% (55–73); P vs 38.4 (31.0–47.5) nm; P Conclusions These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects.

International audience; In the wake of the discovery of numerous large blade workshops at Le Grand-Pressigny site (Indre-et-Loire, France), which initially aroused great interest, the mid-Loire Valley region became central to studies of flint diffusion. Despite the quality of the initial work, the widely shared view now is that the capacity for this concept to continue to provide useful archaeological modelling has diminished. Establishing real and actual correlations between archaeological objects and geological samples remains difficult, making it almost impossible to determine the source of certain materials represented in an archaeological series. In response to this problem, the French collective research project "Réseau de lithothèque en région Centre-Val de Loire" assembled about 30 amateur and professional researchers from various European institutions to work on three strategic missions:- Mission 1: establish a list of current rock-libraries (lithothèques), verify their contents and complete them if necessary;- Mission 2: link the major types of depositional environments with the properties acquired by flint through its life;- Mission 3: spread knowledge and information both within the project and to all interested persons.The project is closely associated with similar French programs already in place in Auvergne-Rhône-Alpes and Aquitaine regions. The ultimate objective is to build a national and international community around a common project, bringing participants together regularly to share knowledge and technical expertise.

Inhibiting the opening of mitochondrial permeability transition pore (mPTP), thereby maintaining the mitochondrial membrane potential and calcium homeostasis, could reduce the induction of cell death. Although recombinant human erythropoietin (rhEpo) and carbamylated erythropoietin (Cepo) were shown to prevent apoptosis after traumatic brain injury (TBI), their impact on mPTP is yet unknown. Thirty minutes after diffuse TBI (impact-acceleration model), rats were intravenously administered a saline solution (TBI-saline), 5000 UI/kg rhEpo (TBI-rhEpo) or 50 μg/kg Cepo (TBI-Cepo). A fourth group received no TBI insult (sham-operated) (n = 11 rats per group). Post-traumatic brain edema was measured using magnetic resonance imaging. A first series of experiments was conducted 2 h after TBI (or equivalent) to investigate the mitochondrial function with the determination of thresholds for mPTP opening and ultrastructural mitochondrial changes. In addition, the intramitochondrial calcium content [Caim] was measured. In a second series of experiments, brain cell apoptosis was assessed at 24 h post-injury. TBI-rhEpo and TBI-Cepo groups had a reduced brain edema compared with TBI-saline. They had higher threshold for mPTP opening with succinate as substrate: 120 (120-150) (median, interquartiles) and 100 (100-120) versus 80 (60-90) nmol calcium/mg protein in TBI-saline, respectively (p 0.05). Similar findings were shown with glutamate-malate as substrate. TBI-rhEpo and Cepo groups had less morphological mitochondrial disruption in astrocytes. The elevation in [Caim] after TBI was not changed by rhEpo and Cepo treatment. Finally, rhEpo and Cepo reduced caspase-3 expression at 24 h post-injury. These results indicate that rhEpo and Cepo could modulate mitochondrial dysfunction after TBI. The mechanisms involved are discussed.

Resume Les pneumopathies necrosantes a Staphylococcus aureus (SA) secreteur de la leucocidine de Panton Valentine (PVL) ont un taux de mortalite eleve, environ 50 % selon des donnees recentes, et concernent principalement des enfants ou des adultes jeunes. Recemment, 2 cas de cette maladie ont ete rapportes chez des jumeaux nouveau-nes avec une evolution favorable. Nous rapportons un autre cas de pneumonie communautaire necrosante a SA sensible a la methicilline (SASM) secreteur de la PVL chez un nourrisson qui avait presente, dans le cadre d’une furonculose familiale, un tableau clinique initial fruste aboutissant neanmoins rapidement au deces. Des cas de pneumopathie necrosante dans cette tranche d’âge commencent a etre decrits, rendant necessaire une large information des cliniciens en raison d’une mortalite importante.

Resume Les services hospitaliers sont quotidiennement confrontes au probleme des traitements medicamenteux personnels des patients. Dans le cadre de la securisation du circuit du medicament, la pharmacie de l’hopital d’Angouleme s’est interessee a l’organisation de la prise en charge de ces traitements. Un etat des lieux prealable a ete realise a l’aide d’un questionnaire dans douze services representatifs de l’hopital. Suite a l’analyse des resultats de cette enquete, une reunion pluridisciplinaire pharmaciens, medecins, et cadres infirmiers a permis d’etablir des recommandations sur la prise en charge des traitements personnels des patients, regroupees dans une procedure validee par la Commission des Medicaments et des Dispositifs Medicaux Steriles.

Mutations in the XNP/ATR-X gene cause several X-linked mental retardation syndromes in humans. The XNP/ATR-X gene encodes a DNA-helicase belonging to the SNF2 family. It has been proposed that XNP/ATR-X might be involved in chromatin remodelling. The lack of a mouse model for the ATR-X syndrome has, however, hampered functional studies of XNP/ATR-X. C. elegans possesses one homolog of the XNP/ATR-X gene, named xnp-1. By analysing a deletion mutant, we show that xnp-1 is required for the development of the embryo and the somatic gonad. Moreover, we show that abrogation of xnp-1 function in combination with inactivation of genes of the NuRD complex, as well as lin-35/Rb and hpl-2/HP1 leads to a stereotyped block of larval development with a cessation of growth but not of cell division. We also demonstrate a specific function for xnp-1 together with lin-35 or hpl-2 in the control of transgene expression, a process known to be dependent on chromatin remodelling. This study thus demonstrates that in vivo XNP-1 acts in association with RB, HP1 and the NuRD complex during development.

Until very recently it was not known whether the invertebrate Caenorhabditis elegans was capable of mounting a specific immune response to protect itself from pathogens. It has only just become clear that this simple nematode in fact possesses a complex innate immune system, involving multiple signalling pathways and an armoury of antimicrobial proteins and peptides. Genetic and microarray approaches are now revealing the molecular cross-talk that exists between the different signalling cascades.

International audience; OBJECTIVES: To investigate the effects of recombinant human erythropoietin on brain oxygenation in a model of diffuse traumatic brain injury. DESIGN: Adult male Wistar rats. SETTING: Neurosciences and physiology laboratories. INTERVENTIONS: Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were intravenously administered with either a saline solution or a recombinant human erythropoietin (5000 IU/kg). A third group received no traumatic brain injury insult (sham-operated). MEASUREMENTS AND MAIN RESULTS: Three series of experiments were conducted 2 hours after traumatic brain injury to investigate: 1) the effect of recombinant human erythropoietin on brain edema using diffusion-weighted magnetic resonance imaging and measurements of apparent diffusion coefficient (n = 11 rats per group); local brain oxygen saturation, mean transit time, and blood volume fraction were subsequently measured using a multiparametric magnetic resonance-based approach to estimate brain oxygenation and brain perfusion in the neocortex and caudoputamen; 2) the effect of recombinant human erythropoietin on brain tissue PO₂ in similar experiments (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 rat per group). Compared with the sham-operated group, traumatic brain injury saline rats showed a significant decrease in local brain oxygen saturation and in brain tissue PO₂ alongside brain edema formation and microvascular lumen collapse at H2. Treatment with recombinant human erythropoietin reversed all of these traumatic brain injury-induced changes. Brain perfusion (mean transit time and blood volume fraction) was comparable between the three groups of animals. CONCLUSION: Our findings indicate that brain hypoxia can be related to microcirculatory derangements and cell edema without evidence of brain ischemia. These changes were reversed with post-traumatic administration of recombinant human erythropoietin, thus offering new perspectives in the use of this drug in brain injury.

Von 2006 bis 2009 wurden auf dem Fundplatz „ Bergeresse“ in Abilly (Departement Indre-et-Loire, Frankreich) auf einer Fläche von 5 000 m2 achtzehn Haufen mit Abschlagprodukten untersucht. Es handelt sich ausschließlich um die Produktionsreste von großen endneolithischen Klingenkernen des Typs „ Butterpfund“. Neben den Resten dieser Schlagabfolge finden sich weitere Klingenabschläge, die der Nachbearbeitung der Butterpfunde entsprechen. Die Entdeckung von Siedlungsresten (Werkzeuge aus bearbeitetem und geschliffenem Stein, Mahlsteine, Keramik…) im Zusammenhang mit zwei Steinhaufen hat gezeigt, dass der Ort, von dem man ursprünglich glaubte, dass er ausschließlich der Bearbeitung des Feuersteins vorbehalten war mit kleinen, von den Abbauzonen des Rohstoffes getrennten Werkstätten, in Wirklichkeit komplexer war. Die Ergebnisse der „ Bergeresse“-Grabungen und eine erneute Überprüfung der Befunde der älteren Grabungen werden die Kenntnisse bereichern und für den Sektor Grand-Pressigny neue Forschungsperspektiven in zahlreiche Richtungen (Rohstoffgewinnung, Funktionsweise der Schlagplätz, Steininventare, Organisation der Arbeitsschritte, Übermittlung der Kenntnisse, chronologisch-kultureller Rahmen…) eröffnen., Between 2006 and 2009, 18 flint knapping workshops have been excavated on a 5.000 m ² area at " Bergeresse" (Abilly, Indre-et-Loire -France). All these workshops result from the Livre-de-beurre long blades production during the late Neolithic. However, beside these chaîne operatoire remains, other blades debitages due to cores rework are present. Rubbish dumps, with knapped and polished tools, grinding stones and ceramic, are associated with two workshops. It means that the site, which was considered as a specifically flint production one with small workshops distinct from the raw material resources, is actually more complex. " Bergeresse" excavation data and a re-examination of the former researches in the Grand-Pressigny area will enable to update many fields of knowledge such as raw materials economy, workshops organisation, blades productions, savoir-faire transmission, chronological and cultural frame., Verjux Christian, Weisser Stella, Millet-Richard Laure-Anne, Leroy Damien. Nouvelles données sur les ateliers de taille du silex du Néolithique final dans la région du Grand-Pressigny : présentation préliminaire du site de "Bergeresse" à Abilly (Indre-et-Loire, France) . In: Revue archéologique de Picardie. Numéro spécial 28, 2011. pp. 467-478.

Introduction L’hypoxie cerebrale post-traumatique peut s’expliquer par un trouble de la diffusion de l’oxygene du a un œdeme perivasculaire [1] . Le mannitol par son action osmotique devrait ameliorer l’oxygenation cerebrale. Neanmoins, les etudes cliniques sur l’oxygenation cerebrale par methode globale ou locale apres perfusion de mannitol sont discordantes [2] . Nous avons etudie l’effet du mannitol sur l’oxygenation cerebrale dans un modele experimental de traumatisme crânien (TC) diffus en utilisant differentes methodes de mesure : IRM, pression partielle tissulaire en oxygene (PtiO2), saturation en oxygene du sinus longitudinal superieur (SsO2). Materiel et methodes Trente minutes apres un TC diffus (modele d’impact acceleration), une solution intraveineuse etait administree soit de mannitol (1 g/kg) (TC-mannitol), soit de serum sale isotonique (TC-saline). Des groupes controles (sham-saline et sham-mannitol) ne subissaient pas de TC. Trois series d’experiences etaient realisees 2 heures apres le TC. La premiere serie d’experience evaluait l’effet du mannitol sur l’œdeme cerebral par le coefficient de diffusion de l’eau (ADC) en IRM, ainsi que la mesure de la saturation locale du parenchyme cerebral en oxygene (lSO2) ( n = 10 par groupe). Cette methode IRM de mesure de l’oxygenation cerebrale combine l’effet BOLD qui depend localement du rapport entre l’oxyhemoglobine et la deoxyhemoglobine, avec la mesure du volume sanguin cerebral. Une deuxieme serie d’experience etudiait l’effet du mannitol sur la PtiO2 et la SsO2 ( n = 5 rats par groupe). Enfin, une troisieme serie d’experience s’interessait a l’etude de l’ultrastructure corticale ( n = 1 par groupe) au moyen de la microscopie electronique. Resultats En comparaison avec le groupe sham-saline, les rats TC-saline presentent une diminution significative de leur delta ADC (1,9 ± 9,1 % vs −10,4 ± 3,7 %, p p p p p p = 0,06 vs TC saline), PtiO2 (41,9 ± 5,8 mmHg, p p Fig. 1 ). Discussion Le mannitol en diminuant l’œdeme perivasculaire limite l’ischemie microcirculatoire et ainsi restaure l’oxygenation cerebrale par une diminution de la distance de diffusion de l’O2.

Summary Background In many animals, the epidermis is in permanent contact with the environment and represents a first line of defense against pathogens and injury. Infection of the nematode Caenorhabditis elegans by the natural fungal pathogen Drechmeria coniospora induces the expression in the epidermis of antimicrobial peptide (AMP) genes such as nlp-29 . Here, we tested the hypothesis that injury might also alter AMP gene expression and sought to characterize the mechanisms that regulate the innate immune response. Results Injury induces a wound-healing response in C. elegans that includes induction of nlp-29 in the epidermis. We find that a conserved p38-MAP kinase cascade is required in the epidermis for the response to both infection and wounding. Through a forward genetic screen, we isolated mutants that failed to induce nlp-29 expression after D. coniospora infection. We identify a kinase, NIPI-3, related to human Tribbles homolog 1, that is likely to act upstream of the MAPKK SEK-1. We find NIPI-3 is required only for nlp-29 induction after infection and not after wounding. Conclusions Our results show that the C. elegans epidermis actively responds to wounding and infection via distinct pathways that converge on a conserved signaling cassette that controls the expression of the AMP gene nlp-29 . A comparison between these results and MAP kinase signaling in yeast gives insights into the possible origin and evolution of innate immunity.

Class Based Queueing (CBQ) is a packet scheduling discipline that enables hierarchical link-sharing. Compared to other algorithms, it is modular and intuitive in a first approach, and so is implemented and used nowadays. In this paper, we adapt the discipline to schedule critical real-time flows mixed with other kinds of traffic, as is necessary in a DiffServ environment. This requires that some guarantees must be provided deterministically, particularly on queueing delay bounds. Yet theoretical delay bounds for CBQ were never expressed in a general case and with end-to-end derivation, because the nesting of mechanisms makes it hard to predict a worst case scenario. Here we study some cases where an analysis is possible, focusing on two variants of CBQ, and we use network calculus technique to set up a bound that seems realistic. We then show simulations to check the precision of our results.

Background & Aims: We have previously reported the role of nitric oxide in colon tumor regression in vivo. The present study was designed to explore the influence of an endogenous nitric oxide donor, glyceryl trinitrate (GTN), on cell death pathways in colon cancer cells. Methods: Human colon cancer cell lines were treated with the NO donor GTN. Apoptosis was identified by morphological criteria and the terminal deoxynucleotidyl transferase–mediated deoxyuridine (TUNEL) method. The mitochondrial transmembrane potential was studied by flow cytometry, cytochrome c release by Western blot, and caspase activation by combining fluorogenic peptide substrates, peptide inhibitors, and immunoblotting. Expression of death receptors was studied by flow cytometry and confocal microscopy. Results: GTN induces a dose- and time-dependent cell death by apoptosis in colon cancer cells. This cell death pathway involves the mitochondria and caspases, mainly caspase-1 and caspase-10. In contrast, caspase-3 activation is a late and limited event. Death receptors are not involved in GTN-mediated cell death, while GTN sensitizes tumor cells to Fas-ligand–induced apoptosis. This permissive effect correlates with an increased expression of Fas receptor and a decreased expression of several endogenous inhibitors of apoptosis (IAPs). Conclusions: Our results indicate that GTN (1) activates an unusual caspase cascade to induce apoptosis in colon cancer cells and (2) sensitizes these cells to Fas-mediated cell death by increasing the expression of Fas and decreasing the expression of several IAPs. GASTROENTEROLOGY 2002;123:235-246

Introduction L’erythropoietine carbamylee (CEPO), denuee d’effets hematologiques deleteres, possede des proprietes neuroprotectrices anti-œdemateuses (d’action meconnue) dans les modeles de traumatisme crânien (TC) [1] . L’aquaporine 4 (AQP4) est une proteine cerebrale tel un canal a eau presente au niveau de la barriere hemato-encephalique. Son role dans la genese et l’evacuation de l’œdeme cerebral (OC) est discute au sein d’une litterature divergente. Nous formulons l’hypothese que l’effet anti-œdemateux de la CEPO pourrait etre medie par une modulation de l’expression et de la localisation des AQP4. Materiel et methodes Cinq groupes de rats Wistar mâles ont ete anesthesies et inclus dans un modele de TC diffus (de type impact acceleration). Les animaux recevaient 30 minutes apres le TC : – de la CEPO a la dose de 50 μg/kg ; – ou du serum physiologique (TC saline) ; – ou un inhibiteur des AQP4, le PMA [2] (phorbol 12-myristate 13-acetate) a la dose de 200 μg/kg/2 heures ; – ou son vehicule le DMSO (dimethylsulfoxide) ; – le groupe Sham n’avait pas de TC (controle). Les rats beneficiaient d’une IRM pre-TC, a H1, H2, puis etaient sacrifies et leur cerveau extrait. Trois series d’experimentation etaient conduites : analyse de l’OC en IRM de diffusion par comparaison des variations d’ADC (coefficient apparent de diffusion), etude de l’expression des AQP4 en RT-PCR et en immunofluorescence (IF) a H2. Resultats (1) Analyse de l’OC en IRM de diffusion ( n = 39 rats). La comparaison de l’ADC entre l’IRM pre-TC et a H2 (Δ ADC) montrait un œdeme post-TC : diminution de l’ADC dans le groupe TC saline (Δ ADC −7,74 % ± 2,7) vs Sham (0,26 % ± 3,4) p p p = 0,01. (2) Expression des AQP4 en RT-PCR a H2 post-TC ( n = 35). On notait une tendance a l’augmentation de l’expression de l’ARNm dans le groupe TC saline vs Sham, et encore plus importante dans le groupe TC CEPO vs Sham ( p = 0,07). Le PMA inhibait l’expression des AQP4 ( p = 0,05). (3) Expression et localisation des AQP4 en IF a H2 post-TC ( n = 28). On observait l’apparition d’un immuno-marquage des AQP4 au niveau capillaire dans les groupes TC, non present chez les Sham et une augmentation du marquage chez les TC CEPO par rapport aux TC saline ( Fig. 1 ). Aucun marquage n’etait observe dans le groupe TC PMA. Le marquage vasculaire etait inchange (anticorps anti-RECA, marqueur endothelial). Discussion La CEPO pourrait diminuer l’œdeme post-TC (en imagerie) grâce a une augmentation de l’expression des AQP4 (observee en RT-PCR et IF). Cela pourrait s’accompagner d’une relocalisation des AQP4 au plus pres de la barriere hemato-encephalique le long des pieds astrocytaires et favoriserait ainsi la sortie de l’eau des cellules [3] . Ces experimentations sont a completer en IF par un co-marquage vasculaire, AQP4 et astrocytaire, en cours.

International audience

Salanova Laure. Du Néolithique final à l'Age du Bronze ancien dans le Centre Nord de la France. In: Bulletin de la Société préhistorique française, tome 98, n°1, 2001. pp. 131-132.

Limited tryptic digestion of native low-density lipoprotein (LDL) (ϱ 1.024- 1.045 g/ml) liberates some 20 - 25% of its surface-exposed protein as soluble, lipid-free peptides (T-peptides). The T-peptides were resolved into twelve subfractions (peaks 1 - 12) by gel filtration chromatography on Bio-Gel P4 in 5 % formic acid, and classified into four major groups on the basis of criteria of size, amino acid composition and predominant C-terminal residue. The first group, peaks 1-4, (∼ 30% of total peptide protein; M, 2600-6000), displayed lysine as preponderant C-terminal (Lys : Arg, 3.7-7.3:1), were acidic in nature (basic:acidic residues, 0.37-0.61:1), and more hydrophobic than holo-apo-LDL. Peaks 1 and 2 contained glycopeptides (four or less by fingerprinting), the monosaccharide composition of which resembled that of LDL glycopeptides of type I1 [Swaminathan, N. & Aladjem, F. (1976) Biochemistry, 15, 1516-15211. The second group, peaks 5 and 6, (∼ 30% of the total; Mr, 1500-2000), were also apparently derived predominantly by cleavage at lysyl peptidyl bonds (Lys:Arg, 4.6-4.9:1), but were distinct in their higher proportion of basic residues (acidic:basic, 0.83-1.05:1). The third group (peaks 7 and 8) contained peptides approx. eight residues in length, with equal proportions (∼ 10%) of arginine and lysine. In contrast, the smaller fragments (2-5 residues) of peaks 9-12 exhibited arginine as major C-terminal residue (Lys:Arg, mean 0.45:1), as well as similar amounts of acidic and basic residues. Examination of the quantitative distribution of lysine and arginine showed 80% of arginines to be present in fragments of eight residues or less, with the majority (45 %) in peptides of 2-5 residues. In contrast, ∼ 70% of total lysines were located in fragments of z 10-20 residues; only ∼ 10% of lysines were in small (2-5 residue) peptides. Arginine appears therefore to occur most often at short (2-5 residues) and lysine at longer (six or more residues) distances from the next lysine or arginine in trypsin-accessible LDL protein. Clusters of a minimum of two positive charges, often featuring arginine, can thus be envisaged. The resemblance of the amino acid profiles of the major peptide subfractions (peaks 1-8) to that of apolipoprotein B further supports the contention that this apoprotein possesses a repetitive-type sequence. Finally, despite evaluation of peptide heterogeneity by fingerprinting, the inferred presence of incompletely-cleaved tryptic peptides in peaks 3, 4 and 5 precludes attribution of a minimal unique amino acid sequence to apolipoprotein B.

Introduction: viral bronchiolitis is the first reason for admission in pediatric intensive care unit (PICU) for babies under two years old during the epidemic season. The main objectives of treatment is to preserve good gas exchanges. Use non-invasive ventilation (NIV) has decreased intubation rates. High flow nasal cannula (HFNC) is more and more use since several years. We chose to define severe bronchiolitis as the need to use an invasive ventilation or a NIV with bi-level positive airway pressure. Our main aim was to bring out clinical or biological factors associated with severe bronchiolitis. Population and methods: a retrospective study during winters 2013/2014, 2014/2015, and 2015/2016 , in HCE (Hôpital Couple Enfant, Grenoble). We included all infants younger than 6 months, hospitalized in PICU for bronchiolitis, and who needed ventilation support. We separated severe bronchiolitis and not severe bronchiolitis in two groups. We compared biological and clinical data at the admission and 4 hours after admission. For each patient, we collected ventilation support at admission and if it was required to escalate ventilation. Results: we analysed 252 patients, 152 were included in the severe bronchiolitis group and 100 in the non-severe group. The patients in the severe group were younger and lighter than patient in the non-severe group. They had more often bacterial coinfections and apnea syndrome. At admission, the PRISM score, the heart rate and the pH were significantly different between the two groups. The improvement of clinical and biological parameters was faster in the non-severe population. Long of stay in PICU was shorter in the non-severe population. During the last three years, we noted that the children were more easily hospitalized in PICU, despite they were affected by less severe bronchiolitis. HNFCT use heavily increased while IV use significantly decreased. Length of stay in PICU was shorter the last season studied (2015-2016). Small weight, bacterial coinfection, presence of apneas, Respiratory Syncytial Virus (RSV) infection, high clinical score of severity (Wang score), high respiratory rate, acidosis and hypercapnia were associated to higher rate of HNFCT failure. Fast response to HNFCT was predictive of a higher probability of its success.Discussion: NIV and HNFCT are effectively used to support infants with distress due to severe bronchiolitis. They led to a decreased rate of intubation. Factors associated with Invasive Ventilation (IV) are the same than those described by other authors. HNFCT ease of use, its good tolerability, its effectiveness, tend to change therapeutic practice and lead to anticipated hospitalization in PICU. HNFCT could lower the length of stay in PICU, alongside the adverse effects due to IV but also NIV. Those results have yet to be confirmed by prospective studies.; Introduction : la bronchiolite est la première cause d’hospitalisation des enfants de moins de 2 ans pendant les saisons épidémiques. Un des enjeux du traitement est le maintien de bons échanges gazeux. L’utilisation de la ventilation non invasive (VNI) a permis la réduction du taux d’intubation. L’oxygénothérapie haut débit (OHD) est utilisée dans le traitement des bronchiolites depuis plusieurs années. Nous avons défini les bronchiolites sévères, par la nécessité d’une ventilation invasive ou non invasive à deux niveaux de pression. L’objectif principal de notre étude était de mettre en évidence des facteurs associés aux bronchiolites sévères. Population et méthodes : étude mono-centrique, rétrospective, de 2013 à 2015. Nous avons classé en deux groupes, grave et non grave, tous les enfants de moins de 6 mois, qui ont été hospitalisés pour bronchiolite dans le service d’USCP-réanimation de l’Hôpital Couple Enfant, avec nécessité de supports ventilatoires. Nous avons comparé les données cliniques et biologiques d’entrée et à 4 heures d’hospitalisation. Nous avons aussi recueilli pour chaque enfant le mode de ventilation choisi, et l’évolution. Résultats : il y avait 252 enfants analysés, 152 dans le groupe bronchiolite grave et 100 dans le groupe non grave. Les enfants du groupe grave étaient plus jeunes et plus légers, ils présentaient plus de surinfections bactériennes et de syndromes apnées-bradycardies. Le score de PRISM et la fréquence cardiaque étaient plus élevés à l’admission, et le pH plus bas dans le groupe grave. L’amélioration était plus rapide dans le groupe non grave. Discussion : Ces résultats sont à confirmer au travers d’études prospectives.