8 research outputs found
Efficacy, tolerability, and safety of an innovative medical device for improving oral accessibility during oral examination in special-needs patients: A multicentric clinical trial.
BackgroundPeople with special needs have high unmet oral healthcare needs, partly because dentists find it difficult to access their oral cavity. The Oral Accessibility Spatula aims to improve oral accessibility. This prospective multicenter interventional open-label non-randomized patient-self-controlled trial assessed the ability of the spatula to improve the oral accessibility of special-needs patients during dental examinations.MethodsThe cohort was a convenience sample of minor and adult patients with special needs due to physical, intellectual, and/or behavioral disorders who underwent dental check-up/treatment in five French tertiary hospitals/private clinics in 2016-2018 and evinced some (Venham-Score = 2-4) but not complete (Venham-Score = 5) resistance to oral examination. After inclusion, patients underwent oral examination without the spatula and then immediately thereafter oral examination with the spatula. Primary outcome was Oral Accessibility Score (0-12 points; higher scores indicate visualization and probing of the tooth sectors). Secondary outcomes were patient toleration (change in Venham-Score relative to first examination), safety, and Examiner Satisfaction Score (0-10; low scores indicate unsatisfactory examination).ResultsThe 201 patients were mostly non-elderly adults (18-64 years, 65%) but also included children (21%), adolescents (11%), and aged patients (3%). One-quarter, half, and one-quarter had Venham-Score = 2, 3, and 4 at inclusion, respectively. The spatula significantly improved Oral Accessibility Score (4.8 to 10.8), Venham-Score (3.1 to 2.6), and Examiner Satisfaction Score (3.4 to 7.2) (all pConclusionThe spatula significantly improved oral access, was safe and well-tolerated by the patients, and markedly improved oral examination quality
The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients
Mutations in Notch3 cause CADASIL (cerebral autosomal dominant adult onset arteriopathy), which leads to stroke and dementia in humans. CADASIL arteriopathy is characterized by major alterations of vascular smooth muscle cells and the presence of specific granular osmiophilic deposits. Patients carry highly stereotyped mutations that lead to an odd number of cysteine residues within EGF-like repeats of the Notch3 receptor extracellular domain. Such mutations may alter the processing or the trafficking of this receptor, or may favor its oligomerization. In this study, we examined the Notch3 expression pattern in normal tissues and investigated the consequences of mutations on Notch3 expression in transfected cells and CADASIL brains. In normal tissues, Notch3 expression is restricted to vascular smooth muscle cells. Notch3 undergoes a proteolytic cleavage leading to a 210-kDa extracellular fragment and a 97-kDa intracellular fragment. In CADASIL brains, we found evidence of a dramatic and selective accumulation of the 210-kDa Notch3 cleavage product. Notch3 accumulates at the cytoplasmic membrane of vascular smooth muscle cells, in close vicinity to but not within the granular osmiophilic material. These results strongly suggest that CADASIL mutations specifically impair the clearance of the Notch3 ectodomain, but not the cytosolic domain, from the cell surface
The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients
Collections d’échantillons biologiques humains pour la recherche : principaux enjeux et conséquences pour le patient ?
Collection of human biological samples for research purpose: Key challenges and patients’ perspectives
Overexpression of the cytokine BAFF and autoimmunity risk
BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. METHODS: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. RESULTS: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.)