Blunted muscle angiogenic training-response in COPD patients versus sedentary controls

International audienceThe impaired skeletal muscle of chronic obstructive pulmonary disease (COPD) patients reduces exercise capacity. Similar to the oxidative muscle fibres, the angio-adaptation of muscle to training may be blunted in these patients, as in other chronic conditions. We therefore compared muscle functional responses and angio-adaptations after training in COPD patients and sedentary healthy subjects (SHS). 24 COPD patients (forced expiratory volume in 1 s 45.6¡17.5% predicted) and 23 SHS (,150 min?week-1 of moderate-to-vigorous exercise) completed a 6-week rehabilitation programme based on individualised moderate-intensity endurance training. Histomorphological muscle analysis and measurements of pro-angiogenic vascular endothelial growth factor (VEGF)-A and anti-angiogenic thrombospondin (TSP)-1 were conducted before and after training. COPD patients and SHS showed improved symptom-limited oxygen consumption and muscle endurance, although improvements were lower in COPD patients (+0.96¡2.4 versus +2.9¡2.6 mL?kg-1 ?min-1 , p,0.05, and +65% versus +108%, p50.06, respectively). The capillary-to-fibre (C/F) ratio increased less in COPD patients than SHS (+16¡10% versus +37¡20%, p,0.05) and no fibre type switch occurred in COPD patients. The VEGF-A/TSP-1 ratio increased in COPD patients and SHS (+65% versus +35%, p,0.05). Changes in C/F and symptom-limited oxygen consumption were correlated (r50.51, p,0.05). In addition to a lack of fibre switch, COPD patients displayed a blunted angiogenic response to training

A pseudo-spectral approach to inverse problems in interface dynamics

An improved scheme for computing coupling parameters of the Kardar-Parisi-Zhang equation from a collection of successive interface profiles, is presented. The approach hinges on a spectral representation of this equation. An appropriate discretization based on a Fourier representation, is discussed as a by-product of the above scheme. Our method is first tested on profiles generated by a one-dimensional Kardar-Parisi-Zhang equation where it is shown to reproduce the input parameters very accurately. When applied to microscopic models of growth, it provides the values of the coupling parameters associated with the corresponding continuum equations. This technique favorably compares with previous methods based on real space schemes.Comment: 12 pages, 9 figures, revtex 3.0 with epsf style, to appear in Phys. Rev.

Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction

International audienceFacioscapulohumeral muscular dystrophy (FSHD),the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms, legs, and trunk. FSHD is genetically linked to contractions of the D4Z4 repeat array causing activation of several genes.One of these maps in the repeat itself and expresses the DUX4 (the double homeobox 4) transcription factor causing a gene deregulation cascade. In addition, analyses of the RNA or protein expression profiles in muscle have indicated deregulations in the oxidative stress response. Since oxidative stress affects peripheral muscle function, we investigated mitochondrial function and oxidative stress in skeletal muscle biopsies and blood samples from patients with FSHD and age-matched healthy controls, and evaluated their association with physical performances.We show that specifically, oxidative stress (lipid peroxidation and protein carbonylation), oxidative damage (lipofuscin accumulation), and antioxidant enzymes (catalase, copper–zinc-dependent super- oxide dismutase, and glutathione reductase) were higher in FSHD than in control muscles. FSHD muscles also presented abnormal mitochondrial function (decreased cytochrome c oxidase activity and reduced ATP synthesis). In addition, the ratio between reduced (GSH) and oxidized glutathione (GSSG) was strongly decreased in all FSHD blood samples as a consequence of GSSG accumulation. Patients with FSHD also had reduced systemic antioxidative response molecules, such as low levels of zinc (a SOD cofactor), selenium (a GPx cofactor involved in the elimination of lipid peroxides), and vitamin C. Half of them had a low ratio of gamma/alpha tocopherol and higher ferritin concentrations. Both systemic oxidative stress and mitochondrial dysfunction were correlated with functional muscle impairment. Mitochondrial ATP production was significantly correlated with both quadriceps endurance (TLimQ) and maximal voluntary contraction (MVCQ) values (rho¼0.79, P¼0.003; rho¼0.62, P¼0.05, respectively). The plasma concentration of oxidized glutathione was negatively correlated with the TLimQ, MVCQ values, and the 2-min walk distance (MWT) values (rho¼0.60, P¼0.03; rho¼0.56, P¼0.04; rho¼0.93, Po0.0001, respectively). Our data characterized oxidative stress in patients with FSHD and demonstrated a correlation with their peripheral skeletal muscle dysfunction. They suggest that antioxidants that might modulate or delay oxidative insult maybe useful in maintaining FSHD muscle functions

Open Data for Global Science

The global science system stands at a critical juncture. On the one hand, it is overwhelmed by a hidden avalanche of ephemeral bits that are central components of modern research and of the emerging ‘cyberinfrastructure’4 for e-Science.5 The rational management and exploitation of this cascade of digital assets offers boundless opportunities for research and applications. On the other hand, the ability to access and use this rising flood of data seems to lag behind, despite the rapidly growing capabilities of information and communication technologies (ICTs) to make much more effective use of those data. As long as the attention for data policies and data management by researchers, their organisations and their funders does not catch up with the rapidly changing research environment, the research policy and funding entities in many cases will perpetuate the systemic inefficiencies, and the resulting loss or underutilisation of valuable data resources derived from public investments. There is thus an urgent need for rationalised national strategies and more coherent international arrangements for sustainable access to public research data, both to data produced directly by government entities and to data generated in academic and not-for-profit institutions with public funding. In this chapter, we examine some of the implications of the ‘data driven’ research and possible ways to overcome existing barriers to accessibility of public research data. Our perspective is framed in the context of the predominantly publicly funded global science system. We begin by reviewing the growing role of digital data in research and outlining the roles of stakeholders in the research community in developing data access regimes. We then discuss the hidden costs of closed data systems, the benefits and limitations of openness as the default principle for data access, and the emerging open access models that are beginning to form digitally networked commons. We conclude by examining the rationale and requirements for developing overarching international principles from the top down, as well as flexible, common-use contractual templates from the bottom up, to establish data access regimes founded on a presumption of openness, with the goal of better capturing the benefits from the existing and future scientific data assets. The ‘Principles and Guidelines for Access to Research Data from Public Funding’ from the Organisation for Economic Cooperation and Development (OECD), reported on in another article by Pilat and Fukasaku,6 are the most important recent example of the high-level (inter)governmental approach. The common-use licenses promoted by the Science Commons are a leading example of flexible arrangements originating within the community. Finally, we should emphasise that we focus almost exclusively on the policy—the institutional, socioeconomic, and legal aspects of data access—rather than on the technical and management practicalities that are also important, but beyond the scope of this article

Tzigani. Caprice pour violon avec accompagnement de piano par Maurice Hayot.

score and part. 35 cm. Sibley Music Library copy autographed

Evaluation de la dyspnee a l'effort

SCOPUS: re.jinfo:eu-repo/semantics/publishe

La dysfonction musculaire du patient Broncho-pneumopathie Chronique Obstructive (à propos de quelques mécanismes impliqués dans l'amélioration de la fonction musculaire induite par les programmes de réentrainement)

Nous ne sommes plus autorisés à parler de la BPCO comme d'une simple maladie respiratoire mais plutôt comme une maladie générale. Parmi les atteintes systémiques, la dysfonction musculaire apparaît comme un facteur clé dans la physiopathologie de la BPCO car elle domine l'évolution de la maladie. Par ailleurs, le mystère autour de l'origine exacte de cette dysfonction reste encore entier. Il est maintenant bien établi qu'au cours des épisodes d'exacerbations, la dysfonction musculaire atteint son paroxysme, de plus en absence d'accompagnement musculaire spécifique la récupération est quasi nulle. Ainsi, les objectifs de ce travail de thèse ont étés la compréhension des mécanismes impliqués, d'une part, dans la dysfonction musculaire périphérique des patients BPCO stables et instables (après épisode d'exacerbation) et, d'autre part, dans l'amélioration de la fonction musculaire après différents programmes de réentraînements à l'effort. Dans le cadre de notre première étude, nous avons rapporté que l'oxydation des protéines, plus particulièrement les protéines mitochondriales était plus élevée dans le quadriceps des patients avec une BPCO stable. De plus, nous avons montré que les épisodes d'exacerbations sont associés à une augmentation de l'oxydation des protéines, au niveau mitochondriales et contractiles, corrélée à une dysfonction musculaire. Dans un second temps, nous avons envisagé un réentrainement par électrostimulation chez les patients en cours d'exacerbation et un réentrainement individualisé au seuil ventilatoire (intensité modérée) pour les patients cliniquement stables. Nos résultats indiquent que les deux programmes d'entraînement proposés préviennent le stress oxydant musculaire et améliorent la fonction musculaire périphérique chez les patients BPCO. Cependant, les adaptations mitochondriales restent limitées chez les patients BPCO stables comparativement aux sujets contrôles. En conclusion, nos résultats montrent que les protéines contractiles et mitochondriales sont la cible d'une augmentation du stress oxydant musculaire particulièrement au cours d'une exacerbation. Par ailleurs, des programmes de réentraînement adaptés à la sévérité de la fonction musculaire préviennent les dommages liés au stress oxydant musculaire et contribuent à l'amélioration de la fonction musculaire périphérique. Ainsi, nous pensons que nos résultats pourront probablement favoriser l'amélioration de la prescription du réentraînement à l'effort chez les patients BPCO.We are no longer allowed to consider COPD as a simple respiratory disease but rather as a systemic disease. Among the systemic effects, muscle dysfunction appears to be a key factor in the pathogenesis of COPD because it strongly influences how the disease will progress. However, the exact origin of muscle dysfunction is still unknown. It is acknowledged that during COPD exacerbations muscle dysfunction is worsened and that, in the absence of post-exacerbation muscle training, recovery is slow and partial. Thus, the objectives of this thesis were first to try to understand the cellular mechanisms involved in the peripheral muscle dysfunction in patients with stable and unstable (after exacerbations) COPD and, then, to assess different programs of physical training to improve muscle function in such patients.Concerning the identification of the mechanisms underlying peripheral muscle dysfunction, we found that protein oxidation, particularly mitochondrial protein oxidation, is higher in the quadriceps of patients with stable COPD than in control subjects. In addition, we have shown that COPD exacerbations are associated with increased muscle oxidative damage of mitochondrial and contractile proteins that is correlated with the level of muscle dysfunction. We then assessed a training protocol using neuromuscular electrostimulation for patients during COPD exacerbation and a training program of moderate intensity (ventilatory threshold) for clinically stable patients. Our results indicate that the two training programs prevent oxidative stress and improve muscle function in COPD patients. However, mitochondrial adaptation is limited in patients with stable COPD compared with controls. In conclusion, our results show that contractile and mitochondrial proteins are the target of increased oxidative stress particularly during COPD exacerbation. However, training programs tailored to the severity of muscle dysfunction can prevent further oxidative damage and contribute to improving muscle function. Our findings might help improving the choice of training programs for patients with COPD.MONTPELLIER-BU Médecine UPM (341722108) / SudocSudocFranceF

Impact de l'inactivité physique et du réentrainement dans la dysfonction musculaire périphérique complexe de la BPCO (au delà du déconditionnement ?)

Les maladies chroniques constituent l'un des défis du 21ème siècle. La Broncho-pneumopathie chronique obstructive est une maladie respiratoire caractéristique de ces maladies, en raison de son caractère hétérogène et de ses répercussions systémiques. Parmi celles-ci, la dysfonction musculaire périphérique est cruciale, mais ses liens avec l'atteinte pulmonaire restent mal expliqués. La réduction d'activité physique a été le premier lien proposé, mais le remodelage musculaire dans la BPCO est bien différent à celui observé chez des sujets déconditionnés (possiblement en raison d'une exposition à la sédentarité plus ancienne et importante), et d'autres facteurs tels le stress oxydant ont été incriminés. La comparaison directe de la dysfonction musculaire périphérique de BPCO à celle de sujets sains sédentaires est limitée par l'hétérogénéité de l'atteinte musculaire. Enfin, chez les patients BPCO, le réentrainement n'a jamais fait la preuve d'adaptations musculaires similaires à celles de sujets sains sédentaires. L'objectif de cette thèse est donc la mise en évidence du rôle exact de la réduction d'activité physique et de l'exercice dans la dysfonction musculaire périphérique hétérogène de la BPCO. Nous montrons que l'exposition à la l'inactivité au cours de la vie n'est pas plus importante dans la BPCO que chez des sujets sains sédentaires. Parallèlement, il existe des phénotypes de dysfonction musculaire dans la BPCO. Cependant, quel que soit le phénotype considéré, il persiste des anomalies ultrastructurales entre patients BPCO et sujets sains de même niveau d'activité physique. Finalement, un même programme de réentrainement à l'effort n'a pas entrainé les mêmes adaptations fonctionnelles, morphologiques et angiogéniques que chez les sujets sains sédentaires.En conclusion, ces différents travaux remettent en cause le paradigme classique de la spirale du déconditionnement dans la BPCO et ouvrent des pistes pour l'optimisation de la réhabilitation respiratoire.Chronic diseases are one of the medical challenges of the 21st century. The chronic obstructive pulmonary disease is paradigmatic of this type of diseases, because of its heterogeneity, and its systemic repercussions. The peripheral muscle dysfunction constitutes a key-repercussion in COPD. However, the links between this muscle dysfunction and the pulmonary impairment remain poorly understood.The physical activity reduction has been the first link proposed. However, the magnitude of structural muscle remodeling in COPD differs to the one of deconditioned sedentary subjects (though, this could be the consequence of greater and older inactivity in COPD), and other factors like the oxidative stress have been incriminated. The peripheral muscle dysfunction in COPD patients has never been directly compared to the one of healthy subjects of the same physical activity level, and is limited by the heterogeneity of the muscle dysfunction in COPD patients. Last, the exercise training has never shown similar muscle response in COPD patients as compared to healthy sedentary subjects. The aim of this PhD Thesis was to understand the exact contribution the physical inactivity and the exercise training in the heterogeneous peripheral muscle, dysfunction in COPD patients.First, we observed that the lifetime physical activity was not greater in COPD patients as compared to lifetime sedentary healthy subjects. In another hand, we showed phenotypes of peripheral muscle dysfunction in COPD patients. However, and whatever the phenotype considered, there was significantly more ultra-structural damage in COPD patients vs. healthy sedentary subjects. Last, a similar exercise training program did not induce similar functional, histo-morphological and angiogenic muscle responses in COPD patients vs. healthy sedentary subjects.Altogether, our work challenges the classical paradigm of the COPD spiral of decline and open doors to research on other specific pathways of the field of muscle dysfunction in COPD in order to optimize the pulmonary rehabilitation.MONTPELLIER-BU Médecine UPM (341722108) / SudocSudocFranceF

Existe-t-il une myopathie chez le patient broncho-pneumopathe chronique obstructif? (rôle du stress oxydant)

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Boundary Object in the design of mobile health technology applications

International audienc