IL-6 Deficiency Attenuates Murine Diet-Induced Non-Alcoholic Steatohepatitis

BACKGROUND:The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH. MATERIALS AND METHODS:Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet. RESULTS:Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals. Despite having a comparable liver steatosis score, IL-6-deficient mice exhibited less lobular inflammation than their wild-type littermates. Liver gene expression of TGF-beta and MCP-1 was also strongly attenuated in mutant mice; a more modest reduction was observed for PPAR-gamma and F4/80 transcripts as well as proteins. Chromatographic analysis of liver lipids demonstrated that MCD diet induced in normal and mutant mice a similar decrease in the ratio of phosphatidylcholine to phosphatidylethanolamine. However, the diet-induced increase in the levels of sphingomyelin and ceramide was less important in IL-6(-/-) mice. CONCLUSION:Altogether, these results indicate that IL-6 deficiency does not block the development of NASH; yet, IL-6 plays a critical role in the accompanying liver inflammation

The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies

Évaluation fonctionnelle des pollicisations de l’index dans les malformations congénitales : apport de la vidéo-assistance

Introduction: The results of index finger pollicisation are usually assessed by performance in simple hand movements included in the Percival score. The purpose of this study was to examine the contribution of video assistance to assess the results of pollicisation in everyday life hand movements. Material and methods: We performed a retrospective study of 22 children who underwent index pollicisation between 1998 and 2012. The mean follow-up was 79 months (18-157 months) and the mean age at surgery was 30 months (12-192 months). The results were evaluated by the Percival score and by examination of functional hand movements in everyday life, as assessed by video assistance. Inter and intra observer concordance was assessed using kappa statistics. Results. Percival's average score was 14,9. Overall, the results of pollicisation were not as good on video-assistance as on the Percival score, in particular when "hidden camera" was used. In particular, functional analysis by video assistance showed that children tended to use their neo thumb in lateral pinch. As with the score of Percival, results were better in patients operated before the age of 2 years and in those without associated anomaly. Conclusion: This study shows that functional assessment by video assistance of hand movements in everyday life after index finger pollicisation provides additional information compared to the score of Percival.Introduction : L’évaluation des pollicisations de l’index repose habituellement sur la réalisation de gestes simples selon le score de Percival. Le but de cette étude a été d’évaluer l’apport d’une évaluation fonctionnelle par vidéo-assistance de l’utilisation de la main dans les gestes de la vie quotidienne. Matériels et méthodes : Nous avons étudié rétrospectivement 22 enfants opérés entre 1998 et 2012 d’une pollicisation de l’index. Le recul moyen était de 79 mois (18-157 mois) et l’âge moyen au moment de la chirurgie de 30 mois (12-192 mois). Les résultats ont été évalués par le score de Percival et en observant la fonctionnalité de la main dans les gestes de la vie quotidienne, exécutés « à la demande » de l’observateur, puis de façon spontanée en « caméra cachée ». La concordance intra et inter-observateur a été évaluée par le test kappa. Résultats. Le score moyen de Percival était de 14,9. Les résultats de la chirurgie étaient globalement moins bons en évaluation par vidéo assistance que par le score de Percival, particulièrement en « caméra cachée ». L’analyse fonctionnelle par vidéo-assistance a notamment montré que les enfants avaient tendance à exclure leur néo pouce et à l’utiliser en pince latéro-digitale. Comme le score de Percival, les résultats étaient meilleurs chez les patients opérés avant l’âge de 2 ans et chez ceux ne présentant pas d’anomalie associée. Conclusion: Cette étude montre que l’analyse fonctionnelle par vidéo-assistance de l’utilisation de la main dans les gestes de la vie quotidienne après pollicisation de l’index apporte des informations complémentaires comparativement au score de Percival

Caractérisation de l'activité hydrosédimentaire dans le Système Turbiditique du Var (NO Méditerranée) et de son enregistrement dans l'archive sédimentaire

In the framework of the HERMES European project, this study aims to characterize the sedimentary processes acting in the Var turbiditic system, their impact on the morphology, and their evolution through time and space. This work uses data acquired along the system, including interface cores, acoustic data, and measurement in the water column (temperature, particulate fluxes, speed and direction of the currents) thanks to mooring lines. The Var turbiditic system is under the influences of the Northern Current and of the Var river by a direct connection. Sedimentary processes are related to gravity-driven currents, oceanic currents which remobilizes sediments and hemipelagic decantation. Gravity-driven processes are dominant and are responsible of 80% of the mean annual sedimentary transport in the system, at the scale of two years (2005-2007). They are characterized by a mean speed of 100 to 600 mm.s-1 and a mean particulate flux of 10 to more than 400 g.m-2.j-1. The combination of the river discharge data and our in-situ measures allows to discriminate the mechanism responsible of their triggering: mass-wasting or river floods. Hyperpycnal turbidity currents, generated by the plunging of the turbid plume are observed for flood extended to the whole hydrographic system, with a river discharge of more than 306 m.s-1 at the river mouth. The past sedimentary processes have also been addressed, by studying the sedimentary deposits. During the last century, the canyon and the valley floor is a pathway for sediments and shows numeral erosive bedforms. Actual sedimentation is episodic and patchy and consists on coarse turbidites. Due to its elevation, the levee is a depositional area, but where only few gravity currents are able to spill over. The dominant facies of inner terraces depends on their elevation above the canyon or channel floor. On low-elevation terraces, erosional processes counterbalance depositional processes. All deposits show erosional bases. Only a few deposits on high-elevation terraces show erosional bases and they record most of the recent processes. Five major types of deposits are recorded in the deposits. They are related to (1) concentrated gravity-currents, and their evolution in (2) high-density turbidity currents, related to large slope failures, (3) hyperpycnal turbidity currents, and (4) surge-like turbidity currents, triggered by shallow retrogressive failures. A fifth kind of sedimentary deposits could be related to the decantation of a turbid plume or to an alteration by bioturbation or bottom currents. These gravity-driven currents are classified in two main groups, as a function of their impact on the morphology. Low-magnitude flows, among which surge-like turbidity currents and hyperpycnal turbidity currents related to yearly floods, constitute the main part of the daily sediment flux. These events are not powerful enough to carry their sediment load into the deep sea, and remain confined in the upper part of the turbidite system (Canyon and Upper Valley). They deposit thin, fine-grained and discontinuous sedimentary sequences, even at a metric scale, and are moreover easily eroded and hardly preserved. High-magnitude flows, among which turbidity currents related to large slope failures or to high-magnitude floods, generate significant changes in the morphology of the turbidite system. They lead to a strong erosion in the canyon and in the valley and provide thick, continuous and recognizable bodies with an extent covering the whole Var system.Le système turbiditique du Var présente la particularité d'être fréquemment parcouru par des écoulements gravitaires. Cela en fait un endroit privilégié pour étudier simultanément les facteurs déclenchant des courants de turbidité, leurs caractéristiques hydrodynamiques, leur contenu particulaire et les dépôts associés. Dans le cadre du projet Européen HERMES (6ème Programme Cadre), nous avons acquis pendant 2 ans dans le canyon du Var et dans la vallée turbiditique (1) des séries temporelles dans la colonne d'eau (30 m et 400 m au dessus du fond) sur la vitesse des courants, la température et le flux particulaire, et (2) des prélèvements répétés par carottage du sédiment de surface. Nos résultats mettent en évidence deux types de transport sédimentaire: (1) des écoulements gravitaires, et (2) des remises en suspension sur le fond par le Courant Nord. L'étude des caractéristiques hydrodynamiques des courants gravitaires permet de préciser nos connaissances sur leur mécanisme de formation. Les courants gravitaires peuvent être initiés par des déstabilisations dans le canyon ou par le plongement en mer de l'eau turbide du fleuve (courant de turbidité hyperpycnal). Ces derniers peuvent être générés lorsque le débit liquide du fleuve franchit un seuil de 306 m3.s-1 à l'embouchure, et à condition que la crue soit étendue à l'ensemble du réseau hydrographique. L'étude combinée des mesures sur les deux années et des faciès sédimentaires dans les dépôts du siècle dernier souligne la prépondérance des courants de turbidité hyperpycnaux, qui représentent 80 % des écoulements gravitaires. De plus, cette étude combinée montre que les écoulements de faible magnitude (résultant de petites instabilités ou de crues annuelles du fleuve) s'arrêtent généralement au débouché de la vallée supérieure et ne déposent du sédiment que sur une terrasse située à 70 m au dessus du fond de la vallée. Les courants gravitaires de grande magnitude (résultant de larges instabilités ou de crues majeures du fleuve) sont fortement érosifs dans la partie du système située avant le pied de pente, et déposent des séquences sédimentaires sur les terrasses, la levée, et localement dans le chenal. Le cadre chrono-stratigraphique établi pour l'étude des séquences sédimentaires permet de mieux contraindre la manière dont ces courants gravitaires sont enregistrés et préservés, à plusieurs échelles de temps