Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

Promoting the use of Motor Function Measure (MFM) as outcome measure in patients with Duchenne Muscular Dystrophy (DMD) treated by corticosteroids

ObjectivesAssessing muscle function is a key step in measuring changes and evaluating the outcomes of therapeutic interventions in Duchenne Muscular Dystrophy (DMD). Regarding the large use of corticosteroids (CS) in this population to delay the loss of function, our goal was to monitor the evolution of motor function in patients with DMD treated by corticosteroids (CS) and to study the responsiveness of Motor Function Measure (MFM) in this population in order to provide an estimation of the number of subject needed for a clinical trial.MethodA total of 76 patients with DMD, aged 5.9 to 11.8 years, with at least 6 months of follow-up and 2 MFM were enrolled, 30 in the CS treated group (8±1.62 y) and 46 in the untreated group (7.91±1.50 y).ResultsThe relationship between MFM scores and age was studied in CS treated patients and untreated patients. The evolution of these scores was compared between groups, on a 6-, 12- and 24-month period by calculating slopes of change and standardized response mean. At 6, 12 and 24 months, significant differences in the mean score change were found, for all MFM scores, between CS treated patients and untreated patients. For D1 subscore specifically, at 6 months, the increase is significant in the treated group (11.3±14%/y; SRM 0.8) while a decrease is observed in the untreated group (–17.8±17.7%/y; SRM 1). At 12 and 24 months, D1 subscore stabilized for treated patients but declined significantly for untreated boys (–15.5±15.1%/y; SRM 1 at 12 mo and–18.8±7.1%/y; SRM 2.6 at 24 mo). 21 patients lost the ability to walk during the study: 6 in the CS treated group (25% at 24 months, mean age: 10.74±1.28 y) and 15 in the untreated group (64.71% at 24 months, mean age: 9.20±1.78 y).Discussion and conclusionPatients with DMD treated by CS present a different course of the disease described in this paper using the MFM. Based on these results, an estimation of the number of patients needed for clinical trial could be done

The evolutionary ecology of complex lifecycle parasites: linking phenomena with mechanisms

Many parasitic infections, including those of humans, are caused by complex lifecycle parasites (CLPs): parasites that sequentially infect different hosts over the course of their lifecycle. CLPs come from a wide range of taxonomic groups-from single-celled bacteria to multicellular flatworms-yet share many common features in their life histories. Theory tells us when CLPs should be favoured by selection, but more empirical studies are required in order to quantify the costs and benefits of having a complex lifecycle, especially in parasites that facultatively vary their lifecycle complexity. In this article, we identify ecological conditions that favour CLPs over their simple lifecycle counterparts and highlight how a complex lifecycle can alter transmission rate and trade-offs between growth and reproduction. We show that CLPs participate in dynamic host-parasite coevolution, as more mobile hosts can fuel CLP adaptation to less mobile hosts. Then, we argue that a more general understanding of the evolutionary ecology of CLPs is essential for the development of effective frameworks to manage the many diseases they cause. More research is needed identifying the genetics of infection mechanisms used by CLPs, particularly into the role of gene duplication and neofunctionalisation in lifecycle evolution. We propose that testing for signatures of selection in infection genes will reveal much about how and when complex lifecycles evolved, and will help quantify complex patterns of coevolution between CLPs and their various hosts. Finally, we emphasise four key areas where new research approaches will provide fertile opportunities to advance this field

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Le difficile diagnostic du syndrome de Kleine-Levin : illustration autour du cas d’un adolescent

International audienceLe syndrome de Kleine-Levin est un trouble neuropsychiatrique appartenant à la catégorie des hypersomnies d’origine centrale. Sa prévalence est estimée à 1 à 5 cas par million d’habitant. Il débute électivement au moment de la puberté (85 % des cas se déclarent au cours de la deuxième décennie). La clinique se caractérise par la survenue d’épisodes d’hypersomnie récurrents d’une durée de quelques jours à plusieurs semaines, associée à des symptômes neurologiques, psychiatriques ou comportementaux. Ce polymorphisme clinique peut être trompeur en présence de symptômes psychiatriques « bruyants » et retarder le diagnostic et le traitement. La cause du syndrome est encore inconnue : des hypothèses auto-immune, inflammatoire ou génétique ont été avancées. La prise en charge consiste à éviter l’alcool, les infections et le manque de sommeil, à utiliser des corticoïdes en crise et du lithium ou du valproate en prévention. Nous présentons le parcours de soins d’un adolescent de 15 ans, qui illustre l’intrication des symptômes neurologiques et psychiatriques et la nécessité de connaître cette sémiologie aux confins de la neuropsychiatrie qui fera éviter des parcours diagnostiques chaotiques

Cerebrospinal fluid metabolomics in West Syndrome: central role of the serine metabolic pathway

Purpose: West Syndrome (WS) is a rare epileptic condition which specifically affects young infants, with a potentially severe outcome. Its pathophysiology remains unclear, which hinders progress in developing targeted medications. Here, we sought to determine whether WS patients have a specific cerebrospinal fluid (CSF) metabolic profile which could help to characterize the alterations involved. Method: CSF samples were collected during the 2010-2016 period from WS patients (n=9). The control group (n=9) included normally developing and seizure-free children who underwent a lumbar puncture (LP). Targeted and untargeted CSF metabolomics analyses were performed by Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS). The metabolic patterns were analyzed by multivariate analysis based on multiple machine-learning methods (i.e. biosigner algorithm including the use of training, test sets and bootstraps) and univariate statistical analysis. Results: Biosigner strategy revealed a significant model discriminating WS and controls from 2 metabolites including serine. The model correctly predicted diagnosis for 83% of subjects. Serine levels were also statistically different between the two groups by univariate analysis (p=0.0023). Conclusion: This is the first metabolomics study in WS. Our results suggest a pivotal need of serine in this disorder. The symptoms observed in WS are consistent with alterations of the serine metabolism pathway. We provide new data concerning this severe epileptic syndrome and highlight the potential value of metabolomics studies in pediatric neurological disorders, even when patients are scarce