11 resultados para IAU MDC

em Université de Lausanne, Switzerland


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Travaux effectués dans le cadre de l'étude "Case Mix" menée par l'Institut universitaire de médecine sociale et préventive de Lausanne et le Service de la santé publique et de la planification sanitaire du canton de Vaud, en collaboration avec les cantons de Berne, Fribourg, Genève, Jura, Neuchâtel, Soleure, Tessin et Valais

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Type I interferon (IFN-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. Many viral infections lead to an acute, transient IFN expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. Robust IFN expression often is conferred by specialized plasmacytoid dendritic cells (pDC) and may depend on positive-feedback amplification via the type I IFN receptor (IFNAR). Here, we show that mice infected with Thogoto virus (THOV), which is an influenza virus-like orthomyxovirus transmitted by ticks, mounted sustained IFN responses that persisted up to 72 h after infection. For this purpose, we used a variant of THOV lacking its IFN-antagonistic protein ML, an elongated version of the matrix (M) protein [THOV(ΔML)]. Of note, large amounts of type I IFN were also found in the serum of mice lacking the IFNAR. Early IFN-α expression seemed to depend on Toll-like receptor (TLR) signaling, whereas prolonged IFN-α responses strictly depended on RIG-I-like helicase (RLH) signaling. Unexpectedly, THOV(ΔML)-infected bone marrow-derived pDC (BM-pDC) produced only moderate IFN levels, whereas myeloid DC (BM-mDC) showed massive IFN induction that was IPS-1-dependent, suggesting that BM-mDC are involved in the massive, sustained IFN production in THOV(ΔML)-infected animals. Thus, our data are compatible with the model that THOV(ΔML) infection is sensed in the acute phase via TLR and RLH systems, whereas at later time points only RLH signaling is responsible for the induction of sustained IFN responses.

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BACKGROUND: The Foot and Ankle Ability Measure (FAAM) is a self reported questionnaire for patients with foot and ankle disorders available in English, German, and Persian. This study plans to translate the FAAM from English to French (FAAM-F) and assess the validity and reliability of this new version.METHODS: The FAAM-F Activities of Daily Living (ADL) and sports subscales were completed by 105 French-speaking patients (average age 50.5 years) presenting various chronic foot and ankle disorders. Convergent and divergent validity was assessed by Pearson's correlation coefficients between the FAAM-F subscales and the SF-36 scales: Physical Functioning (PF), Physical Component Summary (PCS), Mental Health (MH) and Mental Component Summary (MCS). Internal consistency was calculated by Cronbach's Alpha (CA). To assess test re-test reliability, 22 patients filled out the questionnaire a second time to estimate minimal detectable changes (MDC) and intraclass correlation coefficients (ICC).RESULTS: Correlations for FAAM-F ADL subscale were 0.85 with PF, 0.81 with PCS, 0.26 with MH, 0.37 with MCS. Correlations for FAAM-F Sports subscale were 0.72 with PF, 0.72 with PCS, 0.21 with MH, 0.29 with MCS. CA estimates were 0.97 for both subscales. Respectively for the ADL and Sports subscales, ICC were 0.97 and 0.94, errors for a single measure were 8 and 10 points at 95% confidence and the MDC values at 95% confidence were 7 and 18 points.CONCLUSION: The FAAM-F is valid and reliable for the self-assessment of physical function in French-speaking patients with a wide range of chronic foot and ankle disorders.

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Dendritic cells (DCs) are leukocytes specialised in the uptake, processing, and presentation of antigen and fundamental in regulating both innate and adaptive immune functions. They are mainly localised at the interface between body surfaces and the environment, continuously scrutinising incoming antigen for the potential threat it may represent to the organism. In the respiratory tract, DCs constitute a tightly enmeshed network, with the most prominent populations localised in the epithelium of the conducting airways and lung parenchyma. Their unique localisation enables them to continuously assess inhaled antigen, either inducing tolerance to inoffensive substances, or initiating immunity against a potentially harmful pathogen. This immunological homeostasis requires stringent control mechanisms to protect the vital and fragile gaseous exchange barrier from unrestrained and damaging inflammation, or an exaggerated immune response to an innocuous allergen, such as in allergic asthma. During DC activation, there is upregulation of co-stimulatory molecules and maturation markers, enabling DC to activate naïve T cells. This activation is accompanied by chemokine and cytokine release that not only serves to amplify innate immune response, but also determines the type of effector T cell population generated. An increasing body of recent literature provides evidence that different DC subpopulations, such as myeloid DC (mDC) and plasmacytoid DC (pDC) in the lungs occupy a key position at the crossroads between tolerance and immunity. This review aims to provide the clinician and researcher with a summary of the latest insights into DC-mediated pulmonary immune regulation and its relevance for developing novel therapeutic strategies for various disease conditions such as infection, asthma, COPD, and fibrotic lung disease.

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La région-capitale comme principal relais européen vers et depuis l'extérieur Paris est dans le trio de tête des villes globales dans les réseaux mondiaux des entreprises, après Londres et New York, davantage grâce au rayonnement de ses entreprises que par son attractivité aux entreprises étrangères. Sa spécificité tient à son rôle particulier de coordination entre des villes européennes. Très bien placée pour relayer les entrées continentales vers d'autres pays européens, elle occupe un rôle de relais dominant pour la sortie des investissements européens dans le monde en particulier vers le Japon. Par ailleurs, elle est la première ville mondiale en relation avec les villes africaines. Une faiblesse relative de son attractivité La région-capitale ne représente pas la destination première des investissements contrôlés depuis les villes qu'elle investit, notamment en Europe, à l'exception de Bruxelles et Francfort. Elle ne représente la première destination des investissements que pour les deux tiers des villes françaises, et hors d'Europe, elle n'est privilégiée que par les villes africaines. Par ailleurs, elle montre une relative faiblesse dans les activités les plus qualifiées. Vers une métropole francilienne plus high-tech collaborant davantage avec les entreprises étrangères Des mesures incitant les entreprises françaises à davantage s'internationaliser, coopérer avec les entreprises étrangères en créant des joint-ventures à l'exemple de Raytheon et Thalès renforcerait l'attractivité de la métropole francilienne. De même, une meilleure identité du Grand Paris avec la création d'espaces dédiés à l'accueil de secteurs de pointe high tech manquant actuellement de lisibilité et soutenus par de grandes entreprises françaises performantes contribueraient à renforcer son attractivité.

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Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

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Cross-talk between NK cells and dendritic cells (DCs) is critical for the potent therapeutic response to dsRNA, but the receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid [poly(I:C)], similarly engaged human TLR3, whereas only poly(I:C) triggered human RIG-I and MDA5. Both dsRNA enhanced NK cell activation within PBMCs but only poly(I:C) induced IFN-gamma. Although myeloid DCs (mDCs) were required for NK cell activation, induction of cytolytic potential and IFN-gamma production did not require contact with mDCs but was dependent on type I IFN and IL-12, respectively. Poly(I:C) but not polyadenylic-polyuridylic acid synergized with mDC-derived IL-12 for IFN-gamma production by acting directly on NK cells. Finally, the requirement of both TLR3 and Rig-like receptor (RLR) on mDCs and RLRs but not TLR3 on NK cells for IFN-gamma production was demonstrated using TLR3- and Cardif-deficient mice and human RIG-I-specific activator. Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation.

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Paris et sa région constituent un des pôles majeurs des entreprises multinationales dans le monde avec Londres et New York. L'Île-de-France apparaît largement intégrée dans la globalisation des services et de l'industrie. C'est ce qui ressort de l'étude originale d'un million de liens formant les réseaux de filiales directes et indirectes des 3 000 premières entreprises multinationales mondiales.

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NlmCategory="UNASSIGNED">This study is aimed at the determination of the measurement properties of the shoulder function B-B Score measured with a smartphone. This score measures the symmetry between sides of a power-related metric for two selected movements, with 100% representing perfect symmetry. Twenty healthy participants, 20 patients with rotator cuff conditions, 23 with fractures, 22 with capsulitis, and 23 with shoulder instabilities were measured twice across a six-month interval using the B-B Score and shoulder function questionnaires. The discriminative power, responsiveness, diagnostic power, concurrent validity, minimal detectable change (MDC), minimal clinically important improvement (MCII), and patient acceptable symptom state (PASS) were evaluated. Significant differences with the control group and significant baseline-six-month differences were found for the rotator cuff condition, fracture, and capsulitis patient groups. The B-B Score was responsive and demonstrated excellent diagnostic power, except for shoulder instability. The correlations with clinical scores were generally moderate to high, but lower for instability. The MDC was 18.1%, the MCII was 25.2%, and the PASS was 77.6. No floor effect was observed. The B-B Score demonstrated excellent measurement properties in populations with rotator cuff conditions, proximal humerus fractures, and capsulitis, and can thus be used as a routine test to evaluate those patients.