European lipodystrophy registry: background and structure

Abstract: Background: Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy. Results: The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Münster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. Conclusions: A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry. Study registration: ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered

European lipodystrophy registry: background and structure

Abstract: Background: Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with lipodystrophy. Results: The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of lipodystrophy (with the exception of HIV-associated lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Münster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. Conclusions: A European registry for all patients with lipodystrophy will provide a platform for improved research in the area of lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with lipodystrophy are invited to participate in the ECLip Registry. Study registration: ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered

Le Saltus arverne, complexe économique

Der « saltus » ist im Arvernergebiet nicht nur eine Waldsondern auch eine Industriedomane, und dies vorallem wegen des Holzes, dessen Abtranstport iiber die Flusswege des Allier, der Sioule und der Oberen Dordogne erfolgte. Der oekonomische Sektor des Allier-Gehietes ist die Keramik-Industrie von Lezoux, deren Oefen einen enormen Holzverbrauch hatten. Dieses Tannenholz kam aus dem « Bassin des Couzes » (Sault en Valbeleix) aus dem Allagnonbassin (la Pinatelle) und aus den « Monts de la Margeride » (Pinols). Die Waldwirtschaft in diesem Gebiet war sehr rationell und oekonomisch eingerichtet. Sie war mehr empirisch im Sektor Bergbau und Metallurgie : -Aurières des Dômes (Grand Sault et Petit Sault), die Bleimine « de la Sioule », die Goldminen der Oberen Dordognem darunter das « Camp de César » bei la Bessette und die Eisenhûtten und Schmieden bei Le Chavanon. Die hauptsachlichsten archaeologischen Zeugnisse aus dem Saltus sind die Ex-Voto an Silvanus von la Tourette und vom Mont Dore und das archaische Relief der sogenannten « Chapelounne » (Singles), auf welchem die traditionellen Holzhauer — und Mineurwerkzeuge abgebildet sind.The arvern Saltus is both a silvan land property and an industrial estate which is producing a lot of wood (materia) ; that wood is carried by the fluvial ways of the rivers Allier, Sioule, Dordogne. The economical sector of the river Allier is concerning the ceramic industry of Lezoux, whose kilns make use of a large quantity of pine-wood, coming from the basin of the Couzes (Sault en Valbeleix), of the Allagnon (La Pinatelle) and from the Margeride Mounts (Pinols). In that area, the silvan economy is well ordered and rational. It shows more empiric character for mines and metallurgy : Aurières of Monts-Domes (Grand Sault and Petit Sault) « Plumberioe » of the Sioule, Gold-mines of the Dordogne (e.g. the « Camp de Cesar » at la Bessette), « Ferrières » and forges of the Chavanon. The chief archaeological remains of the arvern Saltus are the ex-voto to the god Silvanus (La Tourette and Le Mont-Dore) and the archaic carving, so- called from « la Chapelounne » at Singles, which is representing the usual tools of wood-cutters and mine-workers.Domaine forestier, le saltus arverne est aussi domaine industriel en raison du bois (materia) qu'il produit et dont le transport se fait surtout par les voies fluviales de l'Allier, de la Sioule et de la Haute Dordogne. Le secteur économique de l'Allier est celui de l'industrie céramique de Lezoux dont les fours font une énorme consommation de bois de pin en provenance du bassin des Couzes (Sault en Valbeleix), du bassin de l'Allagnon (la Pinatelle), et des Monts de la Margeride (Pinols). L'économie forestière en ce secteur est réglée et rationnelle. Elle est plus empirique dans le secteur des mines et de la métallurgie : Aurières des Dômes (Grand Sault et Petit Sault), plumberioe de la Sioule, mines d'or de la Haute Dordogne, dont le « camp de César » à la Bessette, ferrières et forges du Chavanon. Les principaux vestiges archéologiques du saltus arverne sont les ex-voto au dieu Sylvain de la Tourette et du Mont-Dore et le bas-relief archaïque, dit de la Chapelounne à Singles, qui représente les outils traditionnels du bûcheron et du mineur.Vigouroux Camille. Le Saltus arverne, complexe économique. In: Revue archéologique du Centre, tome 1, fascicule 3, 1962. pp. 211-220

Des ventes de coupes de bois : thèse pour le doctorat... / par Camille Vigouroux... ; Université de Paris, Faculté de droit

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Therapeutic use of recombinant methionyl human leptin.

International audienceRecombinant methionyl human leptin (r-metHuLeptin) was first used as a replacement therapy in patients bearing inactivating mutations in the leptin gene. In this indication, it was shown since 1999 to be very efficient in inducing a dramatic weight loss in rare children and adults with severe obesity due to the lack of leptin. These first clinical trials clearly showed that r-metHuLeptin acted centrally to reduce food intake, inducing loss of fat mass, and to correct metabolic alterations, immune and neuroendocrine defects. A few years later, r-metHuLeptin was also shown to reverse the metabolic complications associated with lipodystrophic syndromes, due to primary defects in fat storage, which induce leptin deficiency. The beneficial effects, which could be mediated by central and/or peripheral mechanisms, are thought to mainly involve the lowering effects of leptin on ectopic lipid storage, in particular in liver and muscles, reducing insulin resistance. Interestingly, r-metHuLeptin therapy also reversed the hypothalamic-pituitary-gonadal axis dysfunctions associated with hypothalamic amenorrhea. However, if r-metHuLeptin treatment has been shown to be dramatically efficient in leptin-deficient states, its very limited effect in inducing weight loss in common obese patients revealed that, in patients with adequate leptin secretion, mechanisms of leptin resistance and leptin tolerance prevent r-metHuLeptin from inducing any additional effects. This review will present the current data about the effects of r-metHuLeptin therapy in humans, and discuss the recent perspectives of this therapy in new indications

Fatigue- and training-related changes in ‘beta’ intermuscular interactions between agonist muscles

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Peroxisome proliferator‐activated receptor gamma‐ligand‐binding domain mutations associated with familial partial lipodystrophy type 3 disrupt human trophoblast fusion and fibroblast migration

International audienceThe transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is essential for placental development, and alterations in its expression and/or activity are associated with human placental pathologies such as pre-eclampsia or IUGR. However, the molecular regulation of PPARG in cytotrophoblast differentiation and in the underlying mesenchyme remains poorly understood. Our main goal was to study the impact of mutations in the ligand-binding domain (LBD) of the PPARG gene on cytotrophoblast fusion (PPARGE352Q ) and on fibroblast cell migration (PPARGR262G /PPARGL319X ). Our results showed that, compared to cells with reconstituted PPARGWT , transfection with PPARGE352Q led to significantly lower PPARG activity and lower restoration of trophoblast fusion. Likewise, compared to PPARGWT fibroblasts, PPARGR262G /PPARGL319X fibroblasts demonstrated significantly inhibited cell migration. In conclusion, we report that single missense or nonsense mutations in the LBD of PPARG significantly inhibit cell fusion and migration processes

Lipodystrophic syndromes: From diagnosis to treatment

International audienceLipodystrophic syndromes are acquired or genetic rare diseases, characterised by a generalised or partial lack of adipose tissue leading to metabolic alterations linked to strong insulin resistance. They encompass a variety of clinical entities due to primary defects in adipose differentiation, in the structure and/or regulation of the adipocyte lipid droplet, or due to immune-inflammatory aggressions, chromatin deregulations and/or mitochondrial dysfunctions affecting adipose tissue. Diagnosis is based on clinical examination, pathological context and comorbidities, and on results of metabolic investigations and genetic analyses, which together determine management and genetic counselling. Early lifestyle and dietary measures focusing on regular physical activity and avoiding excess energy intake are crucial. They are accompanied by multidisciplinary follow-up adapted to each clinical form. In case of hyperglycemia, antidiabetic medications, with metformin as a first-line therapy in adults, are used in addition to lifestyle and dietary modifications. When standard treatments have failed to control metabolic disorders, the orphan drug metreleptin, an analog of leptin, can be effective in certain forms of lipodystrophy syndrome. Metreleptin therapy indications, prescription and monitoring were recently defined in France, representing a major improvement in patient care