Finger creases lend a hand in Kabuki syndrome.

International audienceKabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS

Safety and efficacy of low-dose sirolimus in the PIK3CA-Related Overgrowth Spectrum

Purpose PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Methods Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Results Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. Conclusion This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Elaboration du premier programme d'éducation thérapeutique du patient en cancérologie à l'hôpital Paul Brousse, IMMPaCT (aboutissement du parcours d'une interne en pharmacie)

PARIS-BIUP (751062107) / SudocSudocFranceF

Removal of pesticide mixtures in a stormwater wetland collecting runoff from a vineyard catchment.

International audienceWetlands can collect contaminated runoff from agricultural catchments and retain dissolved and particle-laden pesticides. However, knowledge about the capacity and functioning of wetland systems with respect to the removal of pesticides is very limited. Here we show that stormwater wetlands can efficiently remove pesticides in runoff from vineyard catchments during the period of pesticide application, although flow and hydrochemical conditions of the wetland largely vary over time. During the entire agricultural season, the inflowing load of nine fungicides, six herbicides, one insecticide and four degradation products was 8.039g whereas the outflowing load was 2.181g. Removal rates of dissolved loads by the wetland ranged from 39% (simazine) to 100% (cymoxanil, gluphosinate, kresoxim methyl and terbuthylazine). Dimethomorph, diuron, glyphosate, metalaxyl and tetraconazole were more efficiently removed in spring than in summer. More than 88% of the input mass of suspended solids was retained, underscoring the capability of the wetland to trap pesticide-laden particles via sedimentation. Only the insecticide flufenoxuron was frequently detected in the wetland sediments. Our results demonstrate that stormwater wetlands can efficiently remove pesticide mixtures in agricultural runoff during critical periods of pesticide application, although fluctuations in the runoff regime and hydrochemical characteristics can affect the removal rates of individual pesticides

Comparative Preclinical Study of Lidocaine and Mepivacaine in Resilient Hyaluronic Acid Fillers

Background: Hyaluronic acid-based filler injections are now well-established aesthetic procedures for the correction of skin tissue defects and volume loss. Filler injections are becoming increasingly popular, with a growing number of injections performed each year. Although classified as a minimally invasive procedure, the introduction of a needle or a canula may remain painful for the patient. A major improvement was achieved with the incorporation of local anesthetics into the formulation for pain relief. Methods: In this study, two well-known anesthetics, lidocaine and mepivacaine, were systematically compared to assess their influence on filler mechanical and biological features. The impact of each anesthetic was monitored in terms of gel rheological properties, stability, durability, and degradation. The release profiles of each anesthetic were also recorded. Finally, the pharmacokinetics of each anesthetic in rats were assessed. Results: For all the rheological and biological experiments performed, lidocaine and mepivacaine influences were comparable. The addition of either anesthetic into a soft-tissue filler showed no significant modifications of the stability, durability, and degradability of the gel, with similar release profiles and pharmacokinetics at an equivalent concentration. Conclusions: Substituting lidocaine with mepivacaine does not impact the properties of the gels, and thus both can be equally incorporated as anesthetics in soft-tissue fillers

Performance of a multi-species-plant illumina beadchip

Since mid-2005, Illumina Infinium® genotyping arrays provide data with good accuracy for thousands of SNPs (single nucleotide polymorphism) in thousands individuals for many organisms including plants. These extensive data used in large studies gave new insight in population and molecular genetics. Nevertheless, flexible high density genotyping tools at reasonable costs are still to be developed. Low cost genotyping assays would allow many applications including control of individuals, marker assisted management and genetic approaches in species where molecular developments have a comparatively low value relative to the cost of SNP arrays. The initial cost and/or the minimum sample number requirement are limiting factors for developing a new genotyping tool. An add-on option on already existing product gives a first opportunity to reduce the cost of a beadchip. Designing a multi-species array could be another alternative to increase the number of SNPs and decrease the minimum number of samples for each species, reaching lower genotyping cost assay per species

Phenotype associated with TAF2 biallelic mutations: a clinical description of four individuals and review of the literature

International audienceTranscription factor IID is a multimeric protein complex that is essential for the initiation of transcription by RNA polymerase II. One of its critical components, the TATA-binding protein-associated factor 2, is encoded by the gene TAF2. Pathogenic variants of this gene have been shown to be responsible for the Mental retardation, autosomal recessive 40 syndrome. This syndrome is characterized by severe intellectual disability, postnatal microcephaly, pyramidal signs and thin corpus callosum. Until now, only three families have been reported separately. Here we report four individuals, from two unrelated families, who present with severe intellectual disability and global developmental delay, postnatal microcephaly, feet deformities and thin corpus callosum and who carry homozygous TAF2 missense variants detected by Exome Sequencing. Taken together, our findings and those of previously reported subjects allow us to further delineate the clinical phenotype associated with TAF2 biallelic mutations

Additional file 1: of Open field study on the efficacy of oral fluralaner for long-term control of flea allergy dermatitis in client-owned dogs in Ile-de-France region

Signalment of 26 FAD-affected dogs initially enrolled in the study. (DOCX 29 kb

Additional file 2: of Open field study on the efficacy of oral fluralaner for long-term control of flea allergy dermatitis in client-owned dogs in Ile-de-France region

Additional data about statistical analyses. (DOCX 131 kb