The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Le rôle des microémulsions dans le transport de médicament à travers la peau: application au rétinol et à l'ibuprofène

Microemulsions are easy to prepare and very stable. They can solubilize different types of molecules and are proposed as a permeation enhancer for percutaneous drug delivery. All these characteristics have inspired scientists and they study this type of system as a possible drug vehicle in topical application. The aim of this work is to find and study a microemulsion system able to be a good drug vehicle for topical application. In order to fulfil our goal, we have studied different types of microemulsions. When they are characterized, we used these to synthesize nanoparticles by direct precipitation in the water cores of the microemulsions. Nanoparticles have been characterized by electronic microscopy, dynamic light scattering and UV visible techniques. The faculty of percutaneous permeation of these formulations have been tested by two methods (dialysis and vertical Franz cells system). Other products, including a commercially available formulation, have been tested too to compare the results and evaluate the permeation aptitude of the microemulsion systems.Les microémulsions présentent de nombreux avantages : facilité de préparation, grande stabilité, capacité de solubilisation de diverses molécules ou leur aptitude à faciliter la perméation de la peau. C’est pourquoi, ces dernières décennies, les scientifiques ont montré un intérêt croissant pour les microémulsions comme vecteur potentiel de principe actif en vue d’une administration topique. L’objectif de cette thèse est dès lors de proposer et d’étudier un système de microémulsion qui pourrait s’avérer être un bon vecteur transcutané de médicaments. Pour ce faire, nous avons étudié différents systèmes de microémulsion. Une fois, ces systèmes bien caractérisés, nous les avons utilisés pour synthétiser des nanoparticules de rétinol et d’ibuprofène par précipitation directe de ces principes actifs dans les cœurs aqueux des microémulsions. Les nanoparticules synthétisées ont également été caractérisées de diverses manières (microscopie, diffusion dynamique de la lumière, UV). Le potentiel de transport de médicaments de ces formulations sera évalué par deux techniques : dialyse et perméation sur cellules de Franz. D’autres formulations, dont un produit commercialement disponible, ont également été évaluées vis-à-vis de leur capacité à véhiculer le même principe actif. Une comparaison des résultats obtenus pour les différentes formulations a permis de rationaliser les aptitudes de transports des microémulsions.(DOCSC02) -- FUNDP, 201

Encres anciennes: utilisation non conventionnelle d'aliments

peer reviewedDe tout temps l’homme utilise des pigments pour peindre. Il y a 27.000 ans déjà, près de Marseille, dans la grotte Cosquer, des fresques furent peintes par des hommes préhistoriques. Il existe deux grandes catégories de pigments et colorants: les naturels et les artificiels. La première catégories contient les pigments minéraux tels que les argiles (ocre jaune ou rouge, argile verte ou brune) mais aussi des pierres (lapis lazuli (bleu)) et les pigments organiques d’origine végétale (gaude (jaune)) ou d’origine animale (murex (pourpre). La deuxième catégorie contient les pigments et colorants artificiels issus de réactions chimiques (minium (orange)) ou bien des mi-végétaux, mi-minéraux comme les encres ferro-galliques classés dans les divers. Après avoir servi pendant plusieurs siècles, tous ces pigments ont été remplacés à la fin du XIXe par des colorants synthétiques issus de la pétrochimie, car ces derniers ont l'avantage de la reproductibilité constante des couleurs. Mais la fin programmée du pétrole suscite un regain d'intérêt pour les préparations naturelles. C'est donc très logiquement que notre laboratoire a décidé de s'intéresser au sujet et en particulier aux encres venant du jus de chou rouge et aux encres ferro-grenadiques en collaboration avec l'Abbaye de Villers-la-Ville

Encres anciennes: l'encre ferro-gallique

L'abstract ainsi que le poster peuvent être obtenus sur demande.<BR>Le poster peut être obtenu sur https://www.researchgate.net/profile/Gilles_Olive/contributions/?ev=prf_act ou bien sur http://orbi.ulg.ac.be/browse?type=authorulg&rpp=20&value=Olive%2C+Gilles+p079922International audienceLes pigments naturels sont connus et utilisés depuis des milliers d'années. En effet, les hommes préhistoriques les employaient déjà pour peindre des fresques dans les grottes qui les abritaient. Un exemple des plus parlant est la grotte Cosquer (-19.000 à -27.000 ans) située à proximité de Marseille. Les pigments et colorants peuvent être classés en deux grandes catégories: les pigments et colorants naturels et les pigments et colorants dits artificiels. Ces catégories se subdivisent elles-mêmes en cinq familles. La première de ces cinq familles regroupent les pigments minéraux parmi lesquels nous retrouvons les argiles (ocre jaune, ocre rouge, argile verte, argile brune mais aussi des pierres telles que les lapis lazuli ou la malachite). Les deuxième et troisième famille, quant à elles, rassemblent les pigments et colorants organiques, c'est-à-dire l'indigo (bleu), la gaude (jaune) et la garance (rouge) tous trois d'origine végétale (famille 2) mais aussi la cochenille domestique (rouge) ou le kermès des teinturiers (rouge carmin) d'origine animale (famille 3). Les deux dernières familles concernent les pigments et colorants artificiels. L'une d'entre elle regroupe ceux qui sont issus des réactions chimiques tels que le vert de gris et le minium. La seconde classe les divers tels que les encres de type ferro-gallique, mi-végétale mi-minérale. Tous ces pigments, bien qu'ayant été utilisés durant des siècles, ont été remplacés par des colorants de synthèse issus de l'industrie pétrolière. En effet, ils ont l'avantage de la reproductibilité dans la préparation contrairement aux pigments naturels. Mais la raréfaction du pétrole provoque un regain d'intérêt pour les préparations naturelles. C'est donc très logiquement que notre laboratoire a décidé de s'intéresser au sujet et en particulier aux encres ferro-galliques en collaboration avec l'Abbaye de Villers-la-Ville.<BR>*** L'abstract ainsi que le poster peuvent être obtenus sur demande. ***<BR>Le poster peut être obtenu sur https://www.researchgate.net/profile/Gilles_Olive/contributions/?ev=prf_act ou bien sur http://orbi.ulg.ac.be/browse?type=authorulg&rpp=20&value=Olive%2C+Gilles+p07992

Old inks: plant-based inks

Thousands of years ago, natural pigments were discovered and they have been used ever since. Indeed, prehistoric people already used them to paint the walls of the caves in which they were living. A significant example of this is the Cosquer cave (-19,000 to -27,000 years) located near Marseilles (France). Pigments and dyes can be classified into two broad categories: natural pigments and dyes and those called artificial. These categories are then subdivided into five families. The first one of these five families includes the mineral pigments. Among these we can find the clays (yellow ochre, red ochre, green clay, brown clay) and the stones like lapis lazuli (blue) and malachite (green). The second and third families gather the organic dyes and pigments. Those that have vegetal origins like indigo (blue), weld (yellow) and madder (red) compose the family 2 and those that have animal origins like cochineal (red) and kermes dyers (carmine) form the family 3. One family includes pigments and dyes stemming from chemical reactions such as verdigris or red lead (family 4) and the other one is made of the miscellaneous inks such as iron-gall type who are vegetal and mineral one (family 5). All these pigments, although they have been used for centuries, have been replaced by synthetic dyes from the oil industry at the end of the 19th century. Indeed, they have the advantage of reproducibility of the properties unlike natural pigments. But the scarcity of oil causes a renewed interest in natural preparations. In such purpose, our laboratory in conjunction with the Abbey of Villers-la-Ville has decided to study natural derivatives for inks and focuses in particular on the extraction of pigments from plants

Old inks: pigments extracted from plants

peer reviewedThousands of years ago, natural pigments were discovered and they have been used ever since. Indeed, prehistoric people already used them to paint the walls of the caves in which they were living. A significant example of this is the Cosquer cave (-19,000 to -27,000 years) located near Marseilles. Pigments and dyes can be classified into two broad categories and five families: natural pigments and dyes and those called artificial. The first one of these five families includes the mineral pigments. Among these we can find the clays (yellow ochre, red ochre, green clay, brown clay) and the stones like lapis lazuli (blue). The second and third families gather the organic dyes and pigments. Those that have vegetal origins like indigo (blue) and madder (red) compose the second family and those that have animal origins like cochineal (red) and kermes dyers (carmine) form the third family. One family includes pigments and dyes stemming from chemical reactions such as verdigris or red lead (family 4) and the other one is made of the miscellaneous inks such as iron-gall type who are vegetal and mineral one (family 5). All these pigments, although they have been used for centuries, have been replaced by synthetic dyes from the oil industry at the end of the 19th century. Indeed, they have the advantage of reproducibility of the properties unlike natural pigments. But the scarcity of oil causes a renewed interest in natural preparations. We report the extraction of pigments from plants

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n=17, normal cognition, treatable seizures), 2) intermediate epilepsy (n=36, mild ID, partially pharmacoresponsive), 3) developmental and epileptic encephalopathy (DEE, n=191, severe ID, majority pharmacoresistant), 4) generalized epilepsy (n=21, mild to moderate ID, frequently with absence seizures), and 5) affected individuals without epilepsy (n=25, mild to moderate ID). Groups 1-3 presented with early-onset (median: four months) focal or multifocal seizures and epileptic discharges, whereas the onset of seizures in group 4 was later (median: 39 months) with generalized epileptic discharges. The epilepsy was not classifiable in 143 individuals. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin insensitive human NaV1.6 channels and whole-cell patch clamping. Two variants causing DEE showed a strong gain-of-function (GOF, hyperpolarising shift of steady-state activation, strongly increased neuronal firing rate), and one variant causing BFIE or intermediate epilepsy showed a mild GOF (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (LOF, reduced current amplitudes, depolarising shift of steady-state activation, reduced neuronal firing). Including previous studies, functional effects were known for 165 individuals. All 133 individuals carrying GOF variants had either focal (76, groups 1-3), or unclassifiable epilepsy (37), whereas 32 with LOF variants had either generalized (14), no (11) or unclassifiable (5) epilepsy; only two had DEE. Computational modeling in the GOF group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. GOF variant carriers responded significantly better to sodium channel blockers (SCBs) than to other anti-seizure medications, and the same applied for all individuals of groups 1-3.In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that SCBs present a therapeutic treatment option in early onset SCN8A-related focal epilepsy