En guise d’introduction…

Comme nous l’avions annoncé dans Anabases 3 (p. 252-258), c’est pour amorcer la mise en œuvre de la seconde phase du projet ND@GR (celle de la révision et de l’enrichissement de l’ouvrage) que nous avons organisé, Corinne Bonnet et moi-même, le 24 mars 2006, à Toulouse, une journée d’étude intitulée Les dictionnaires de l’Antiquité : le Daremberg, Saglio et Pottier hier et aujourd’hui. Cette journée, à laquelle ont participé les trois équipes de recherche toulousaines travaillant sur l’Antiq..

Synthèse et bilan d’une exploration préliminaire

Cette journée fut particulièrement enrichissante car nombre de participants (intervenants, invités, simples auditeurs) ont alimenté les discussions. Cette dynamique, finalement peu courante dans ce genre de manifestation, s’explique par le fait que les sujets abordés portaient moins sur des points de connaissance très pointue que sur l’évaluation de la pertinence même du projet et les possibles modalités de sa mise en œuvre. La principale question soulevée fut celle de savoir si en définitiv..

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.</p

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.</p

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype

Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study.

International audienceBACKGROUND: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. METHODS: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA-IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59-71 have been followed during 4 years. Among these women, 166 had already used HRT. RESULTS: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21-0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47-0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA-IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users (P=0.61). CONCLUSION: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route

Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study.

International audienceOBJECTIVES: This trial sought to assess the influence of omeprazole on clopidogrel efficacy. BACKGROUND: Clopidogrel has proved its benefit in the treatment of atherothrombotic diseases. In a previous observational study, we found clopidogrel activity on platelets, tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, to be diminished in patients receiving proton pump inhibitor (PPI) treatment. METHODS: In this double-blind placebo-controlled trial, all consecutive patients undergoing coronary artery stent implantation received aspirin (75 mg/day) and clopidogrel (loading dose, followed by 75 mg/day) and were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. Clopidogrel effect was tested on days 1 and 7 in both groups by measuring platelet phosphorylated-VASP expressed as a platelet reactivity index (PRI). Our main end point compared PRI value at the 7-day treatment period in the 2 groups. RESULTS: Data for 124 patients were analyzed. On day 1, mean PRI was 83.2% (standard deviation [SD] 5.6) and 83.9% (SD 4.6), respectively, in the placebo and omeprazole groups (p = NS), and on day 7, 39.8% (SD 15.4) and 51.4% (SD 16.4), respectively (p < 0.0001). RESULTS: Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation

Diagnostic value of single complete compression ultrasonography in pregnant and postpartum women with suspected deep vein thrombosis: prospective study

To assess the safety of using single complete compression ultrasonography in pregnant and postpartum women to rule out deep vein thrombosis

Convergence entre l’analyse biostatistique et les méthodes d’inversion hiérarchique bayésienne pour la recherche et la validation de biomarqueurs par spectrométrie de masse

International audienceIn this communication, we are presenting an overview on the methods in biostatistical analysis and Bayesian hierarchical inversion we are studying on the BHI-PRO project for research and validation of biomarkers based on mass spectrometry in MALDI and MRM mode. We are also expliciting the performance criteria used and giving some first experimental results. In MRM mode, we are showing on a colorectal cancer cohort using the LFABP and PDI biomarkers a relevant improvement of the sensibility for a specificity satisfying the minimum requirement for a screening test.Dans cette communication, nous présentons une vue d’ensemble des méthodes d’analyse biostatistique et d’inversion hiérarchique Bayésienne que nous étudions sur le projet BHI-PRO pour la recherche et la validation de biomarqueurs par spectrométrie de masse en mode MALDI et MRM. Nous avons aussi explicité les critères de performance utilisés et présenter des premiers résultats expérimentaux. En mode MRM, nous avons montré sur une cohorte de cancer colorectal, en utilisant la LFABP et la PDI comme biomarqueurs, une amélioration significative de la sensibilité pour une spécificité correspondant aux performances demandées pour un test de dépistage

Convergence entre l’analyse biostatistique et les méthodes d’inversion hiérarchique bayésienne pour la recherche et la validation de biomarqueurs par spectrométrie de masse

International audienceIn this communication, we are presenting an overview on the methods in biostatistical analysis and Bayesian hierarchical inversion we are studying on the BHI-PRO project for research and validation of biomarkers based on mass spectrometry in MALDI and MRM mode. We are also expliciting the performance criteria used and giving some first experimental results. In MRM mode, we are showing on a colorectal cancer cohort using the LFABP and PDI biomarkers a relevant improvement of the sensibility for a specificity satisfying the minimum requirement for a screening test.Dans cette communication, nous présentons une vue d’ensemble des méthodes d’analyse biostatistique et d’inversion hiérarchique Bayésienne que nous étudions sur le projet BHI-PRO pour la recherche et la validation de biomarqueurs par spectrométrie de masse en mode MALDI et MRM. Nous avons aussi explicité les critères de performance utilisés et présenter des premiers résultats expérimentaux. En mode MRM, nous avons montré sur une cohorte de cancer colorectal, en utilisant la LFABP et la PDI comme biomarqueurs, une amélioration significative de la sensibilité pour une spécificité correspondant aux performances demandées pour un test de dépistage