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Background: Hypercholesterolemia is considered a major risk factor for pancreatitis, atherosclerosis and coronary heart disease. Cholesteryl ester transfer protein gene polymorphisms are known to be associated with changes in lipid levels. We investigated the association between a polymorphism in the CETP gene (D442G) with plasma lipid levels and CETP activity in patients with hypercholesterolemia. Methods: This case/control study that be done in Hamadan university of medical sciences (from October 2008 to September 2009), included 102 patients with hypercholesterolemia and 200 healthy individuals. Polymerase chain reaction and restriction fragment length polymorphisms were used to determine genotypic distribution and allelic frequencies of polymorphisms. The plasma CETP activity was measured by a kit in a fluorescence spectrometer. Lipid concentrations were measured by routine biochemical and enzymatic assays. Results: Plasma cholesteryl ester transfer protein activity was significantly higher in the cases than the controls (P0.05). Plasma HDL-C, LDL-C and TC were higher in both groups with GG and DG genotypes than with DD genotype, whereas serum CETP activity was lower in GG genotype compared with other genotypes (GD or DD), (P

International audience; CONTEXT:Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of de novo and recurrent bladder cancer.OBJECTIVE:To identify a highly sensitive and specific biomarker candidate set with potential clinical utility in bladder cancer.MATERIALS AND METHODS:Urinary biomarker concentrations were determined by ELISA. The performance of individual markers and marker combinations was assessed using ROC analysis.RESULTS:A five-biomarker panel (IL8, MMP9, VEGFA, PTGS2 and EN2) was defined from the candidate set.DISCUSSION AND CONCLUSION:This panel showed a better overall performance than the best individual marker. Further validation studies are needed to evaluate its clinical utility in bladder cancer.

Background and PurposeParkinson’s disease (PD) is usually diagnosed clinically from classical motor symptoms, while definitive diagnosis is made postmortem, based on the presence of Lewy bodies and nigral neuron cell loss. -Synuclein (ASYN), the main protein component of Lewy bodies, clearly plays a role in the neurodegeneration that characterizes PD. Additionally, mutation in the SNCA gene or copy number variations are associated with some forms of familial PD. Here, the objective of the study was to evaluate whether olesoxime, a promising neuroprotective drug can prevent ASYN-mediated neurotoxicity. Experimental ApproachWe used here a novel, mechanistically approachable and attractive cellular model based on the inducible overexpression of human wild-type ASYN in neuronally differentiated human neuroblastoma (SHSY-5Y) cells. This model demonstrates gradual cellular degeneration, coinciding temporally with the appearance of soluble and membrane-bound ASYN oligomers and cell death combining both apoptotic and non-apoptotic pathways. Key ResultsOlesoxime fully protected differentiated SHSY-5Y cells from cell death, neurite retraction and cytoplasmic shrinkage induced by moderate ASYN overexpression. This protection was associated with a reduction in cytochrome c release from mitochondria and caspase-9 activation suggesting that olesoxime prevented ASYN toxicity by preserving mitochondrial integrity and function. In addition, olesoxime displayed neurotrophic effects on neuronally differentiated SHSY-5Y cells, independent of ASYN expression, by promoting their differentiation. Conclusions and ImplicationsBecause ASYN is a common underlying factor in many cases of PD, olesoxime could be a promising therapy to slow neurodegeneration in PD.

Parkinson's disease (PD) is usually diagnosed clinically from classical motor symptoms, while definitive diagnosis is made postmortem, based on the presence of Lewy bodies and nigral neuron cell loss. α-Synuclein (ASYN), the main protein component of Lewy bodies, clearly plays a role in the neurodegeneration that characterizes PD. Additionally, mutation in the SNCA gene or copy number variations are associated with some forms of familial PD. Here, the objective of the study was to evaluate whether olesoxime, a promising neuroprotective drug can prevent ASYN-mediated neurotoxicity.We used here a novel, mechanistically approachable and attractive cellular model based on the inducible overexpression of human wild-type ASYN in neuronally differentiated human neuroblastoma (SHSY-5Y) cells. This model demonstrates gradual cellular degeneration, coinciding temporally with the appearance of soluble and membrane-bound ASYN oligomers and cell death combining both apoptotic and non-apoptotic pathways.Olesoxime fully protected differentiated SHSY-5Y cells from cell death, neurite retraction and cytoplasmic shrinkage induced by moderate ASYN overexpression. This protection was associated with a reduction in cytochrome c release from mitochondria and caspase-9 activation suggesting that olesoxime prevented ASYN toxicity by preserving mitochondrial integrity and function. In addition, olesoxime displayed neurotrophic effects on neuronally differentiated SHSY-5Y cells, independent of ASYN expression, by promoting their differentiation.Because ASYN is a common underlying factor in many cases of PD, olesoxime could be a promising therapy to slow neurodegeneration in PD.

International audience

International audience

Scopo dell'articolo è la presentazione di ALT-Web, ovvero l'Atlante Lessicale Toscano in rete. ALT-Web è stato ideato per rendere il patrimonio linguistico-culturale testimoniato dall'Atlante Lessicale Toscano una risorsa educativa realmente disponibile in modo che possa fornire un contributo alla conservazione della memoria dell'identità culturale toscana e al contempo costituisca un prezioso punto di riferimento per lo studio di dinamiche linguistiche sia a livello areale sia a livello socio-culturale. La sua collocazione in rete porta inevitabilmente ALT-Web a rivolgersi a una vasta gamma di utenti non più circoscritta agli addetti ai lavori (ovvero dialettologi, linguisti, etno-linguisti), ma che include anche insegnanti, operatori culturali (ad esempio, personale di musei e di istituzioni culturali pubbliche e private) fino al cittadino navigatore di Internet che voglia capire di più della propria identità linguistica e culturale. Il vasto e variegato bacino di utenza a cui intende rivolgersi ALT-Web ha portato alla trasformazione della versione informatizzata dell'Atlante Lessicale Toscano (conosciuta come DBT-ALT) in una rete ipertestuale con modalità e funzionalità di accesso differenziate in relazione alle diverse classi di utenza; a questo aspetto, è legata l'altra interpretazione dell'acronimo ALT-Web, ovvero quella di "ALT come rete". L'articolo illustra aspetti del processo di progettazione e realizzazione dell'opera che rivestono un qualche interesse per il linguista e il dialettologo. In particolare, dopo un breve excursus che riepiloga le caratteristiche principali della risorsa di partenza, l'articolo illustra la progettazione e realizzazione di ALT-Web, partendo dall'analisi dei requisiti e la definizione delle caratteristiche generali per arrivare ad aspetti più specifici che riguardano le modalità di accesso ai materiali e la normalizzazione dei materiali dialettali in trascrizione fonetica.

The paper presents an on-line dialectal resource, ALT-Web, which gives access to the linguistic data of the Lexical Atlas of Tuscany or Atlante Lessicale Toscano, a specially designed linguistic atlas in which lexical data have both a diatopic and diastratic characterisation. The paper illustrates ALT-Web with particular emphasis on: 1) the dialectal data representation model; 2) the access modalities to the ALT dialectal corpus designed to produce an output tailored to the specific needs of the different classes of users (both professionals and common citizens); 3) ontology-based search. These represent three main features which differentiate ALT-Web both from the previous digitalised ALT version and, most interestingly, from other on-line dialectal resources. At the time of writing, this is the first resource of this type in Italy, and one of the few at the international level.