Carriers of the fragile X mental retardation 1 (FMR1) premutation allele present with increased levels of cytokine IL-10.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited late-onset neurodegenerative disorder, characterized both by neurological and cognitive deficits. It is caused by the expansion of CGG repeats (55 to 200 repeats) in the noncoding region of the fragile X mental retardation 1 (FMR1) gene. Abnormal immunological patterns are often associated with neurodegenerative disorders and implicated in their etiology. We therefore investigated the immune status of FXTAS patients, which had not been assessed prior to this study. METHOD: Peripheral blood mononuclear cells (PBMCs) were collected from 15 asymptomatic FMR1 premutation carriers and 20 age-matched controls. Concentrations of three cytokines (IL-6, IL-8, IL-10) were measured in PBMC supernatants using ELISA assays. RESULTS: We found a significant increase in the concentration of the major anti-inflammatory cytokine IL-10 in supernatants of PBMCs derived from premutation carriers, when compared with controls (P = 0.019). This increase correlated significantly with the number of CGG repeats (P = 0.002). CONCLUSIONS: Elevated IL-10 levels were observed in all premutation carriers, before appearance of the classical neurological symptoms; therefore, IL-10 may be one of the early biomarkers of FXTAS.

Les sites fragiles autosomiques. [[Autosomal fragile sites].

It is possible to distribute the 17 autosomic fragile sites presently known in three categories according to their sensitivity: BrdU-sensitive sites (10q25, 16q22, 17p12), distamycin A-sensitive sites (16q22, 17p12) and folate- and thymidilate-sensitive sites (2q11-q14, 3p14, 6p23, 7p11, 8q22, 9p21, 9q32, 10q23, 11q13, 11q23, 12q13, 16p12, 16q23, 17p12, 20p11). Four fundamental problems are discussed, first the relation between the presence of a fragile site and the phenotype, secondly the incidence of autosomic sites, third the origin of fragility (particularity of DNA structure, defect of the DNA/proteins binding and abnormal arrangement of chromatin, abnormality of the metaphasic scaffold) and fourth the localization of fragile sites.

Translating molecular advances in fragile X syndrome into therapy: a review.

Fragile X syndrome is an inherited disease with cognitive, behavioral, and neurologic manifestations, resulting from a single genetic mutation. A variety of treatments that target individual symptoms of fragile X syndrome are currently utilized with limited efficacy. Research in animal models has resulted in the development of potential novel pharmacologic treatments that target the underlying molecular defect in fragile X syndrome, rather than the resultant symptoms. This review describes recent advances in our understanding of the molecular basis of fragile X syndrome and summarizes the ongoing clinical research programs.

Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.

Les anticoagulants oraux directs en 2015 chez le patient âgé: focus chez le sujet fragile

Depuis les études princeps de phase III de non-inf ériorité comparant les anticoagulants oraux directs (AOD) à la warfarine, de nombreuses études ont essayé de répondre à la question de l'efficacité et de la sécurité d'utilisation des AOD chez les patients âgés. Ces études sont des études de sous-groupes complémentaires issues des études princeps ou des études de pharmacovigilance en postmarketing utilisant des données médicoéconomiques à grande échelle. De nombreux biais, par définition, peuvent entraîner une distorsion des résultats dans de telles études, rendant leur interprétation prudente. Aucun essai randomisé contrôlé n'a à ce jour comparé les AOD à la warfarine chez des patients de 80 ans ou plus et a fortiori chez des sujets âgés fragiles. En pratique, chez le patient âgé fragile, il n'y a pas de consensus quant au choix des anticoagulants à prescrire en cas de fibrillation atriale (FA) et de la maladie thromboembolique veineuse (MTEV). Quant au choix de l'AOD à privilégier chez le sujet âgé, faute d'études de comparaison directe disponibles à ce jour, il apparaît difficile de se prononcer. Toutefois, les données disponibles, tant sur le plan pharmacologique que celles issues des études complémentaires, semblent montrer que le dabigatran offre un profil bénéfice/risque moins favorable que les autres AOD. Néanmoins, les résultats prometteurs de l'idarucizumab, antidote du dabigatran, pourraient contribuer à améliorer ce rapport à l'avenir.

Les symbioses agro-industrielles en Afrique de l'Ouest : évaluation du potentiel d'une nouvelle stratégie pour un développement durable

RésuméCette thèse traite de l'utilisation des concepts de Symbiose Industrielle dans les pays en développement et étudie le potentiel de cette stratégie pour stimuler un développement régional durable dans les zones rurales d'Afrique de l'Ouest. En particulier, lorsqu'une Symbiose Industrielle est instaurée entre une usine et sa population alentour, des outils d'évaluation sont nécessaires pour garantir que le projet permette d'atteindre un réel développement durable. Les outils existants, développés dans les pays industrialisés, ne sont cependant pas complètement adaptés pour l'évaluation de projets dans les pays en développement. En effet, les outils sont porteurs d'hypothèses implicites propres au contexte socio-économique dans lequel ils ont été conçus.L'objectif de cette thèse est de développer un cadre méthodologique pour l'évaluation de la durabilité de projets de Symbiose Industrielle dans les pays en développement.Pour ce faire, je m'appuie sur une étude de cas de la mise en place d'une Symbiose Industrielle au nord du Nigéria, à laquelle j'ai participé en tant qu'observatrice dès 2007. AshakaCem, une usine productrice de ciment du groupe Lafarge, doit faire face à de nombreuses tensions avec la population rurale alentour. L'entreprise a donc décidé d'adopter une nouvelle méthode inspirée des concepts de Symbiose Industrielle. Le projet consiste à remplacer jusqu'à 10% du carburant fossile utilisé pour la cuisson de la matière crue (calcaire et additifs) par de la biomasse produite par les paysans locaux. Pour ne pas compromettre la fragile sécurité alimentaire régionale, des techniques de lutte contre l'érosion et de fertilisation naturelle des sols sont enseignées aux paysans, qui peuvent ainsi utiliser la culture de biomasse pour améliorer leurs cultures vivrières. A travers cette Symbiose Industrielle, l'entreprise poursuit des objectifs sociaux (poser les bases nécessaires à un développement régional), mais également environnementaux (réduire ses émissions de CO2 globales) et économiques (réduire ses coûts énergétiques). Elle s'ancre ainsi dans une perspective de développement durable qui est conditionnelle à la réalisation du projet.A travers l'observation de cette Symbiose et par la connaissance des outils existants je constate qu'une évaluation de la durabilité de projets dans les pays en développement nécessite l'utilisation de critères d'évaluation propres à chaque projet. En effet, dans ce contexte, l'emploi de critères génériques apporte une évaluation trop éloignée des besoins et de la réalité locale. C'est pourquoi, en m'inspirant des outils internationalement reconnus comme l'Analyse du Cycle de Vie ou la Global Reporting Initiative, je définis dans cette thèse un cadre méthodologique qui peut, lui, être identique pour tous les projets. Cette stratégie suit six étapes, qui se réalisent de manière itérative pour permettre une auto¬amélioration de la méthodologie d'évaluation et du projet lui-même. Au cours de ces étapes, les besoins et objectifs en termes sociaux, économiques et environnementaux des différents acteurs sont déterminés, puis regroupés, hiérarchisés et formulés sous forme de critères à évaluer. Des indicateurs quantitatifs ou qualitatifs sont ensuite définis pour chacun de ces critères. Une des spécificités de cette stratégie est de définir une échelle d'évaluation en cinq graduations, identique pour chaque indicateur, témoignant d'un objectif totalement atteint (++) ou pas du tout atteint (--).L'application de ce cadre méthodologique à la Symbiose nigériane a permis de déterminer quatre critères économiques, quatre critères socio-économiques et six critères environnementaux à évaluer. Pour les caractériser, 22 indicateurs ont été définis. L'évaluation de ces indicateurs a permis de montrer que le projet élaboré atteint les objectifs de durabilité fixés pour la majorité des critères. Quatre indicateurs ont un résultat neutre (0), et un cinquième montre qu'un critère n'est pas atteint (--). Ces résultats s'expliquent par le fait que le projet n'en est encore qu'à sa phase pilote et n'a donc pas encore atteint la taille et la diffusion optimales. Un suivi sur plusieurs années permettra de garantir que ces manques seront comblés.Le cadre méthodologique que j'ai développé dans cette thèse est un outil d'évaluation participatif qui pourra être utilisé dans un contexte plus large que celui des pays en développement. Son caractère générique en fait un très bon outil pour la définition de critères et indicateurs de suivi de projet en terme de développement durable.SummaryThis thesis examines the use of industrial symbiosis in developing countries and studies its potential to stimulate sustainable regional development in rural areas across Western Africa. In particular, when industrial symbiosis is instituted between a factory and the surrounding population, evaluation tools are required to ensure the project achieves truly sustainable development. Existing tools developed in industrialized countries are not entirely suited to assessing projects in developing countries. Indeed, the implicit hypotheses behind such tools reflect the socioeconomic context in which they were designed. The goal of this thesis is to develop a methodological framework for evaluating the sustainability of industrial symbiosis projects in developing countries.To accomplish this, I followed a case study about the implementation of industrial symbiosis in northern Nigeria by participating as an observer since 2007. AshakaCem, a cement works of Lafarge group, must confront many issues associated with violence committed by the local rural population. Thus, the company decided to adopt a new approach inspired by the concepts of industrial symbiosis.The project involves replacing up to 10% of the fossil fuel used to heat limestone with biomass produced by local farmers. To avoid jeopardizing the fragile security of regional food supplies, farmers are taught ways to combat erosion and naturally fertilize the soil. They can then use biomass cultivation to improve their subsistence crops. Through this industrial symbiosis, AshakaCem follows social objectives (to lay the necessary foundations for regional development), but also environmental ones (to reduce its overall CO2 emissions) and economical ones (to reduce its energy costs). The company is firmly rooted in a view of sustainable development that is conditional upon the project's execution.By observing this symbiosis and by being familiar with existing tools, I note that assessing the sustainability of projects in developing countries requires using evaluation criteria that are specific to each project. Indeed, using generic criteria results in an assessment that is too far removed from what is needed and from the local reality. Thus, by drawing inspiration from such internationally known tools as Life Cycle Analysis and the Global Reporting Initiative, I define a generic methodological framework for the participative establishment of an evaluation methodology specific to each project.The strategy follows six phases that are fulfilled iteratively so as to improve the evaluation methodology and the project itself as it moves forward. During these phases, the social, economic, and environmental needs and objectives of the stakeholders are identified, grouped, ranked, and expressed as criteria for evaluation. Quantitative or qualitative indicators are then defined for each of these criteria. One of the characteristics of this strategy is to define a five-point evaluation scale, the same for each indicator, to reflect a goal that was completely reached (++) or not reached at all (--).Applying the methodological framework to the Nigerian symbiosis yielded four economic criteria, four socioeconomic criteria, and six environmental criteria to assess. A total of 22 indicators were defined to characterize the criteria. Evaluating these indicators made it possible to show that the project meets the sustainability goals set for the majority of criteria. Four indicators had a neutral result (0); a fifth showed that one criterion had not been met (--). These results can be explained by the fact that the project is still only in its pilot phase and, therefore, still has not reached its optimum size and scope. Following up over several years will make it possible to ensure these gaps will be filled.The methodological framework presented in this thesis is a highly effective tool that can be used in a broader context than developing countries. Its generic nature makes it a very good tool for defining criteria and follow-up indicators for sustainable development.

Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation.

BACKGROUND: Male carriers of the FMR1 premutation are at risk of developing the fragile X-associated tremor/ataxia syndrome (FXTAS), a newly recognised and largely under-diagnosed late onset neurodegenerative disorder. Patients affected with FXTAS primarily present with cerebellar ataxia and intention tremor. Cognitive decline has also been associated with the premutation, but the lack of data on its penetrance is a growing concern for clinicians who provide genetic counselling. METHODS: The Mattis Dementia Rating Scale (MDRS) was administered in a double blind fashion to 74 men aged 50 years or more recruited from fragile X families (35 premutation carriers and 39 intrafamilial controls) regardless of their clinical manifestation. Based on previous publications, marked cognitive impairment was defined by a score <or=123 on the MDRS. RESULTS: Both logistic and survival models confirmed that in addition to age and education level, premutation size plays a significant (p<0.01 and p<0.03 for logistic and survival model, respectively) role in cognitive impairment. The estimated penetrance of marked cognitive impairment in our sample (adjusted for the mean age 63.4 years and mean education level 9.7 years) for midsize/large (70-200 CGG) and small (55-69 CGG) premutation alleles was 33.3% (relative risk (RR) 6.5; p = 0.01) and 5.9% (RR 1.15; p = 0.9) respectively. Penetrance in the control group was 5.1%. CONCLUSIONS: Male carriers of midsize to large premutation alleles had a sixfold increased risk of developing cognitive decline and the risk increases with allele size. In addition, it was observed that cognitive impairment may precede motor symptoms. These data provide guidance for genetic counselling although larger samples are required to refine these estimates.

Early white matter alterations in men predisposed to FXTAS revealed by MT imaging.

Introduction: The Fragile X - associated Tremor Ataxia Syndrome (FXTAS) is a recently described, and under-diagnosed, late onset (≈ 60y) neurodegenerative disorder affecting male carriers of a premutation in the Fragile X Mental Retardation 1 (FMR1) gene. The premutation is an CGG (Cytosine-Guanine-Guanine) expansion (55 to 200 CGG repeats) in the proximal region of the FMR1 gene. Patients with FXTAS primarily present with cerebellar ataxia and intention tremor. Neuroradiological features of FXTAS include prominent white matter disease in the periventricular, subcortical, middle cerebellar peduncles and deep white matter of the cerebellum on T2-weighted or FLAIR MR imaging (Jacquemmont 2007, Loesch 2007, Brunberg 2002, Cohen 2006). We hypothesize that a significant white matter alteration is present in younger individuals many years prior to clinical symptoms and/or the presence of visible lesions on conventional MR sequences and might be detectable by magnetization transfer (MT) imaging. Methods: Eleven asymptomatic premutation carriers (mean age = 55 years) and seven intra-familial controls participated to the study. A standardized neurological examination was performed on all participants and a neuropsychological evaluation was carried out before MR scanning performed on a 3T Siemens Trio. The protocol included a sagittal T1-weighted 3D gradient-echo sequence (MPRAGE, 160 slices, 1 mm^3 isotropic voxels) and a gradient-echo MTI (FA 30, TE 15, matrix size 256*256, pixel size 1*1 mm, 36 slices (thickness 2mm), MT pulse duration 7.68 ms, FA 500, frequency offset 1.5 kHz). MTI was performed by acquiring consecutively two set of images; first with and then without the MT saturation pulse. MT images were coregistered to the T1 acquisition. The MTR for every intracranial voxel was calculated as follows: MTR = (M0 - MS)/M0*100%, creating a MTR map for each subject. As first analysis, the whole white matter (WM) was used to mask the MTR image in order to create an histogram of the MTR distribution in the whole tissue class over the two groups examined. Then, for each subject, we performed a segmentation and parcellation of the brain by means of Freesurfer software, starting from the high resolution T1-weighted anatomical acquisition. Cortical parcellations was used to assign a label to the underlying white matter by the construction of a Voronoi diagram in the WM voxels of the MR volume based on distance to the nearest cortical parcellation label. This procedure allowed us to subdivide the cerebral WM in 78 ROIs according to the cortical parcellation (see example in Fig 1). The cerebellum, by the same procedure, was subdivided in 5 ROIs (2 per each hemisphere and one corresponding to the brainstem). For each subject, we calculated the mean value of MTR within each ROI and averaged over controls and patients. Significant differences between the two groups were tested using a two sample T-test (p<0.01). Results: Neurological examination showed that no patient met the clinical criteria of Fragile X Tremor and Ataxia Syndrome yet. Nonetheless, premutation carriers showed some subtle neurological signs of the disorder. In fact, premutation carriers showed a significant increase of tremor (CRST, T-test p=0.007) and increase of ataxia (ICARS, p=0.004) when compared to controls. The neuropsychological evaluation was normal in both groups. To obtain general characterizations of myelination for each subject and premutation carriers, we first computed the distribution of MTR values across the total white matter volume and averaged for each group. We tested the equality of the two distributions with the non parametric Kolmogorov-Smirnov test and we rejected the null-hypothesis at a p=0.03 (fig. 2). As expected, when comparing the asymptomatic permutation carriers with control subjects, the peak value and peak position of the MTR values within the whole WM were decreased and the width of the distribution curve was increased (p<0.01). These three changes point to an alteration of the global myelin status of the premutation carriers. Subsequently, to analyze the regional myelination and white matter integrity of the same group, we performed a ROI analysis of MTR data. The ROI-based analysis showed a decrease of mean MTR value in premutation carriers compared to controls in bilateral orbito-frontal and inferior frontal WM, entorhinal and cingulum regions and cerebellum (Fig 3). The detection of these differences in these regions failed with other conventional MR techniques. Conclusions: These preliminary data confirm that in premutation carriers, there are indeed alterations in "normal appearing white matter" (NAWM) and these alterations are visible with the MT technique. These results indicate that MT imaging may be a relevant approach to detect both global and local alterations within NAWM in "asymptomatic" carriers of premutations in the Fragile X Mental Retardation 1 (FMR1) gene. The sensitivity of MT in the detection of these alterations might point towards a specific physiopathological mechanism linked to an underlying myelin disorder. ROI-based analyses show that the frontal, parahippocampal and cerebellar regions are already significantly affected before the onset of symptoms. A larger sample will allow us to determine the minimum CGG expansion and age associated with these subclinical white matter alterations.

Current standards and progress in understanding and treatment of GIST.

Gastrointestinal stromal tumours (GIST), despite being rare, pose a relevant medical problem from the viewpoint of diagnosis and management. GIST are fragile, liable to metastasize and often located in delicate structures. Surgical options, therefore, are limited. In the last decade an improved understanding of the molecular mechanisms of the disease has resulted in novel modes of treatment. The introduction of systemic tyrosine kinase inhibitor therapy with imatinib has significantly improved the outcome of the disease and prolonged the survival of GIST patients. For many patients the acute threat of a deadly cancer has been transformed into a manageable chronic condition. Drug safety, tolerability and compliance, subjects of concern in all long-term therapies, have proven to be acceptable for the tyrosine kinase inhibitor imatinib. The present paper provides a compact overview of the epidemiology, pathophysiology and morphology of GIST, with special reference to the underlying molecular biology. Relevant aspects of diagnosis, therapy and monitoring of the disease are reviewed with particular emphasis on the available clinical evidence and recent guidelines.

Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.

Babel heureuse : pour lire la traduction

Résumé de la thèse : Babel heureuse. Pour lire la traduction Lire la traduction : telle est l'expérience que cette étude cherche à explorer. Pour ce faire, on a renoncé à un discours critique ou normatif qui subsumerait la question de l'expérience de lecture de la traduction à la question de ce que devrait être cette expérience. En effet, les exigences traditionnelles vis-à-vis de la traduction s'énoncent souvent en des termes comme « fidélité », « adéquation », « justesse » qui valorisent l'identification, l'assimilation de la traduction à l'original et donc son idéale indistinction. Les descriptions de la traduction en termes de « transport », de « passages », etc. tendent également à la considérer comme une médiation idéalement transparente et donc indifférente pour celui qui la lit. La théorie littéraire et la philosophie sont elles aussi en décalage par rapport à la question de la lecture de la traduction. Certes, la lecture y joue un rôle assez primordial, mais la traduction y est extrêmement marginalisée. Elle n'occupe généralement qu'une fonction documentaire, historique ou sociologique, mais la lecture des oeuvres littéraires et philosophiques reste largement le privilège de ceux qui les lisent dans l'original. En outre, les notions principales de la poétique - notamment la question de la voix, de l'auteur, du rapport entre littérature et langue - se trouvent élaborés comme si la traduction n'offrait aucune expérience spécifique. Le décentrement disciplinaire de cette recherche apparaît moins comme une difficulté, mais bien comme l'une de ses impulsions essentielles. Il permet, par un certain 'dehors', de rendre les discours sur la traduction et la littérature à rebours et partant d'en interroger les évidences. Il s'agit alors d'être sensible non seulement à la manière dont la lecture de la traduction emporte les textes, les dynamise et les transforme, mais aussi comment, en retour, cette performance amène à reconsidérer ce que nous appelons 'littérature' et 'traduction'. Lire la traduction, c'est donc aussi inquiéter le discours à partir duquel la traduction se donne à penser : une lecture fragile et souple qui soustrait la traduction à toute tentative d'appropriation et la laisse valoir comme événement d'une étrangeté. Pour explorer cette expérience, cette étude propose des lectures précises de plusieurs philosophes (notamment Descartes, Foucault, Gadamer, Benjamin et Derrida) en considérant à la fois ce qu'ils ont dit - ou parfois significativement passé sous silence - de la traduction et, réciproquement, la manière dont leur pensée procède par traduction. De plus, quatre chapitres sont consacrés à des lectures multilingues de Beckett et de Dürrenmatt permettant de poser certaines questions importantes : qui parle dans une traduction ? Quelle compréhension donne-t-elle à lire ? Quelle impulsion et quelle continuation constitue-t-elle pour l'écriture ? La traduction apparaît alors dans sa performance ouvrante, offrant une littérature encore à inventer.

Whole-Body Vibration Training Elevates Creatine-Kinase Levels in Sedentary Subjects

METHODS: 20 inactive (10 male, 10 female) underwent a single typical WBV session, with a total of 27 minutes of exercise on an oscillating platform at 26 Hz, involving upper and lower body muscles. Each exercise lasted 90 seconds, with 40 seconds pauses inbetween. Muscle enzymes (CK, transaminase, LDH, troponin I) were measured before, at 24, 48 and 96 hours post exercise. Lactate was measured immediately after the session. Muscle aches were assessed during 4 days post-exercise.RESULTS: Subjects' mean age was 23.0 ± 3.5 (male), 22.4 ± 1.4 (female), BMI 22.8 ± 2.3 and 22.1 ± 1.9, and all had been inactive for at least 12 months. Post exercise lactatemia was 10.0 ± 2.4 and 6.9 ± 2.4. CK elevation was significant (at least doubling of baseline values) in 1 male and 4 female subjects, while they remained at baseline values for the remaining 15 subjects. One female subject peaked at 3520 U/l at 96 hours post exercise, and all but one peaked at the same late time. Troponin and CK-MB never increased. No correlation was found between muscle soreness and CK levels.CONCLUSIONS: WBV can elicit important anaerobic processes reflected by the high lactacidemia, and CK elevation was significant in 25 % of subjects, peaking at the fourth day after exercise for 80 % of those. Such exercises should not be regarded as trivial and "easy" as they are advertised, since they can provoke important anaerobia and CK elevation. Many fragile patients or patients treated for cardiovascular disease could benefit from WBV but it is important to recognise these potential effects, especially in those treated with statins, known to cause a myopathy and CK elevation. Before considering a side effect of an important therapeutic agent, doctors should be aware of the possible interaction with not-so-harmless exercising machines.

Immunology taught by lung dendritic cells.

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.

Appartenances en fête: entre l'ordinaire et le spectaculaire

Résumé Alors que les pratiques religieuses régulières diminuent et que les groupes religieux majoritaires perdent des membres formellement enregistrés, une évènementisation de l'appartenance religieuse peut être observée depuis environ deux décennies. Dans un premier exemple, l'auteure montre que le réseau transnational de la confrérie soufie des Mourides resserre les liens entre adeptes dans un contexte migratoire qui tend à fragiliser les relations sociales. La confrérie y fait face à travers une spectacularisation de la pratique religieuse, occupant l'espace public à Harlem ou, dans une moindre mesure, à Paris. Le second exemple traite du pèlerinage aux Saintes et Saints d'Afrique dans la ville valaisanne de Saint Maurice. Ce dernier fut inventé par l'Église catholique suisse afin d'attirer des migrants africains, mais aussi afin de redynamiser une pratique religieuse ordinaire en perte de vitesse. L'évènement a lieu en même temps que le pèlerinage de Namugongo en Ouganda, réunissant plus d'un demi-million de personnes. Les communautés évènementielles ainsi créées sont-elles durables ou plutôt liquides ? Abstract While regular religious practice is decreasing and the major religious groups are losing formally registered members, a 'spectacularization' of religious belonging can be observed over the last two decades. The author presents two examples to support this argument. In the first, the transnational network of the Murids, a Sufi brotherhood, has tried to reinforce the relations between its members, which become fragile during migration. The brotherhood occupies a public space in Harlem, and, to a lesser extent, in Paris, in a spectacularization of religious belonging, in order to remain attractive to migrants. The second example deals with the pilgrimage dedicated to African Saints in the Swiss town of Saint Maurice. This event was invented by the missionary service of the Swiss Catholic Church in order to attract African migrants, but also in order to make ordinary religious practice more appealing. The event takes place at the same time as the Ugandan pilgrimage of Namugongo, which assembles more than half a million people. However, are these 'event communities' sustainable or ephemeral?

Cyclododecane exposure in the field of conservation and restoration of art objects

PURPOSE: Recent work practices in the conservation and restoration involve the use of cyclododecane (CDD, CAS 294-62-2) to protect fragile artifacts during their handling or transportation. Little is known about its toxicity, and no previous exposure has been reported. A short field investigation was conducted to characterize the exposure conditions to both CDD vapors and aerosols.METHODS: Measurements were conducted in the laboratory of conservation and restoration of the archeological service in Bern (Switzerland). Three indoor and four outdoor typical work situations, either during brush or spray gun applications, were investigated. Measurements were performed on charcoal adsorbent tube and analyzed by a gas chromatograph equipped with a flame ionization detector.RESULTS: Measurements have been conducted during both brush and spray gun applications. Indoor exposures were of 0.75-15.5 mg/m(3), while outdoors exposures were 19.5-53.9 mg/m(3). Exposures appear to be extremely localized due to both physicochemical properties and application methods of the CDD. Vapor exposure increases dramatically with the confinement of the workplace.CONCLUSION: Preventive measures should be undertaken to limit as much as possible these exposures. Field work in confined areas (ditches, underground) is of particular concern. CDD-coated artifacts or materials should be stored in ventilated areas to avoid delayed exposures. [Authors]