Beta2-Adrenoreceptor agonist inhibits antigen cross-presentation by dendritic cells

Despite widespread usage of β-adrenergic receptor (AR) agonists and antagonists in current clinical practice, our understanding of their interactions with the immune system is surprisingly sparse. Among the AR expressed by dendritic cells (DC), β2-AR can modify in vitro cytokine release upon stimulation. Because DC play a pivotal role in CD8(+) T cell immune responses, we examined the effects of β2-AR stimulation on MHC class I exogenous peptide presentation and cross-presentation capacities. We demonstrate that β2-AR agonist-exposed mature DC display a reduced ability to cross-present protein Ags while retaining their exogenous peptide presentation capability. This effect is mediated through the nonclassical inhibitory G (Gαi/0) protein. Moreover, inhibition of cross-presentation is neither due to reduced costimulatory molecule expression nor Ag uptake, but rather to impaired phagosomal Ag degradation. We observed a crosstalk between the TLR4 and β2-AR transduction pathways at the NF-κB level. In vivo, β2-AR agonist treatment of mice inhibits Ag protein cross-presentation to CD8(+) T cells but preserves their exogenous MHC class I peptide presentation capability. These findings may explain some side effects on the immune system associated with stress or β-agonist treatment and pave the way for the development of new immunomodulatory strategies

Empiric antimicrobial therapy for ventilator-associated pneumonia after brain injury

International audienceIssues regarding recommendations on empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) have emerged in specific populations.To develop and validate a score to guide empiric therapy in brain-injured patients with VAP, we prospectively followed a cohort of 379 brain-injured patients in five intensive care units. The score was externally validated in an independent cohort of 252 brain-injured patients and its extrapolation was tested in 221 burn patients.The multivariate analysis for predicting resistance (incidence 16.4%) showed two independent factors: preceding antimicrobial therapy ≥48 h (p\textless0.001) and VAP onset ≥10 days (p\textless0.001); the area under the receiver operating characteristic curve (AUC) was 0.822 (95% CI 0.770-0.883) in the learning cohort and 0.805 (95% CI 0.732-0.877) in the validation cohort. The score built from the factors selected in multivariate analysis predicted resistance with a sensitivity of 83%, a specificity of 71%, a positive predictive value of 37% and a negative predictive value of 96% in the validation cohort. The AUC of the multivariate analysis was poor in burn patients (0.671, 95% CI 0.596-0.751).Limited-spectrum empirical antimicrobial therapy has low risk of failure in brain-injured patients presenting with VAP before day 10 and when prior antimicrobial therapy lasts \textless48 

Développement durable et apprentissages non-linéaires : devenir durable par le biais d'une démarche collective et sensible

L'organisation du travail comme nous la connaissons encore aujourd'hui engendre des maux qui dépassent les simples limites de l'espace organisationnel. Ce mémoire de recherche examine le rapport à soi et aux autres à travers le processus d'apprentissage collectif et transformationnel dans un contexte de développement durable et particulièrement via l'axe social. À travers une recherche-action participative, nous avons exploré les possibilités offertes par une approche sensible, centrée sur les capacités des individus et d'un groupe à se redéfinir et à laisser émerger des pistes de solutions. L'approche exploratoire ici utilisée a été mise en œuvre via différentes pratiques lors d'un colloque international, en juillet 2011. Cette étude de terrain participe à une meilleure compréhension des approches menant à une organisation respectueuse du travail et elle sert à étayer l'intuition selon laquelle la prise en compte des valeurs dans lesquelles s'ancrent ces changements d'ordre transformationnel est importante dans la réussite de ces projets. Cette réflexion s'attardera aux processus de changements non linéaires dont le modèle en U d'Otto Scharmer (2009), ainsi qu'à la capacité d'un groupe à se questionner, à chercher à se redéfinir et à mettre ses aptitudes cognitives au service d'une co-création. Il s'agira de pouvoir cerner l'innovation et le savoir collectif et de s'intéresser à l'utilisation d'une approche sensible en tant que vecteur d'une mémoire sensible dans les processus de changements collectifs. Cette mise en action dans un milieu déjà sensibilisé au développement durable ainsi que l'analyse de la rencontre avec un groupe qui franchira des étapes de changement individuel et collectif non-linéaire nous permettra, en somme, de co-construire une relation et d'explorer si le sensible et une communication centrée sur les interactions offrent un accès à une meilleure compréhension des possibles, un futur en émergence (Ibid.) et d'aller à la redécouverte d'une humanité oubliée.\ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : développement durable, apprentissages non-linéaires, Théorie U, complexité, organisation

Tissue functions mediated by β3-adrenoceptors—findings and challenges

As β3-adrenoceptor agonists metamorphose from experimental tools into therapeutic drugs, it is vital to obtain a comprehensive picture of the cell and tissue functions mediated by this receptor subtype in humans. Human tissues with proven functions and/or a high expression of β3-adrenoceptors include the urinary bladder, the gall bladder, and other parts of the gastrointestinal tract. While several other β3-adrenoceptor functions have been proposed based on results obtained in animals, their relevance to humans remains uncertain. For instance, β3-adrenoceptors perform an important role in thermogenesis and lipolysis in rodent brown and white adipose tissue, respectively, but their role in humans appears less significant. Moreover, the use of tools such as the agonist BRL 37344 and the antagonist SR59230A to demonstrate functional involvement of β3-adrenoceptors may lead in many cases to misleading conclusions as they can also interact with other β-adrenoceptor subtypes or even non-adrenoceptor targets. In conclusion, we propose that many responses attributed to β3-adrenoceptor stimulation may need re-evaluation in the light of the development of more selective tools. Moreover, findings in experimental animals need to be extended to humans in order to better understand the potential additional indications and side effects of the β3-adrenoceptor agonists that are beginning to enter clinical medicine

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions

Overview of the current use of levosimendan in France: a prospective observational cohort study

Abstract Background Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. Method The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. Results The patients included ( n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock ( n = 250, 41.5%), decompensated heart failure ( n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment ( n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation ( n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. Conclusions We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied

Diagnosis and management of heparin-induced thrombocytopenia

International audienc

L'environnement sonore urbain

The urban soudscape that we actually know comes from the evolution of teenies and of our ways of life. The noise pollution sharess our every day life in transport, work or at home, we have to admit that citizen' annoyance is growing up ; the effect on health and on behaviors diminish the quality of urban life. Polotician try to answer by legislating technical or financialconditions. The resarchers try to know more about the technical field and the acoustic comfort linked with the individual perceptions. Nevertheless the leaders fail with diagnostic and forecast measumients. A collaboration between différents parties is necessary to give up with costly reabiliting situations and to privilege the acoustic comfort of the citizens.L'environnement sonore urbain que nous connaissons actuellement résulte de l'évolution des techniques et des modes de vie. Les nuisances sonores accompagnent notre vie quotidienne dans les transports, le travail ou/et dans l'habitat. Force est de reconnaître que la gêne des citadins croît et les effets sur la santé, sur les comportements altèrent la qualité de vie en ville. Les politiques tentent de répondre en légiférant suivant l'état des techniques et les moyens financiers. De leur côté, les chercheurs tentent d' approfondir les connaissances tant dans le domaine technique que dans la qualité sonore des espaces en relation avec la perception de l'individu. Toutefois, les décideurs manquent d'outils de diagnostics et de prévision pour agir efficacement contre ces nuisances. Une collaboration des différents acteurs est nécessaire pour en finir avec des situations de rattrapages coûteuses et privilégier le confort sonore des citadins.Rozec Valérie. L'environnement sonore urbain. In: Villes en parallèle, n°28-29, décembre 1999. Ville et environnement. Approche psychosociologique. pp. 102-123

Étude épidémiologique et analyse de la prévention des Troubles Musculo-Squelettiques chez les praticiens masseur-kinésithérapeute en Bretagne

TMS represent nearly 75% of professional diseases and physiotherapists have their share.Preventing these problems is one of the targets of the health and work plan of 2016-2020. This study has been designed to collect data on prevalence, causes and preventive measures linked to TMSMéthod : Distribution by mail during 6 weeks of a questionnaire about TMS to physiotherapists working in Brittany.On 58 responses, 40 are included in the study. The questions subjects are risks factors, location and type of TMS and personal strategies.Results : 50 % of the interwees have TMS. The main touched area is the hand or the wrist. Different risks factors are highlighted at bio-mechanical level (posture, repetition, long efforts) or at technical level (handling, massage).Conclusion : The study results show that TMS of the upper limb are frequent for the physiotherapists population working in Brittany. Facing this professional risk, physiotherapists seem to put in place preventive measures theoretically efficient.Les TMS représentent près de 75% des maladies professionnelles. Les masseur-kinésithérapeutes ne sont pas épargnés. La prévention de ces affections figure dans les priorités du plan santé et travail 2016-2020. L'étude a été conçue afin de recueillir des données sur la prévalence, les causes et la prévention lié au TMS.Méthode : Diffusion durant 6 semaines d'un questionnaire traitant des TMS par mail au MK exerçant en Bretagne. Sur 58 retours, 40 questionnaires sont inclus dans l'étude. Les questions traitent des facteurs de risques, de la localisation, du type et des stratégies personnels.Résultats : 50% des Mk sondés expriment des TMS. L'atteinte principale des TMS se situe dans la région poignet/main. Différents facteurs de risques sont mis en évidence au niveau biomécaniques (postures, répétition, effort prolongés) et des techniques (manutention, massage).Conclusion : Selon les résultats de cette étude, les TMS du membres supérieurs sont fréquents chez les MK exercant en Bretagne. Face à l'exposition de la profession au TMS, les MK semblent mettre en place divers moyens de prévention théoriquement efficace