Spinocerebellar ataxia type 17: Report of a family with reduced penetrance of an unstable Gln(49 )TBP allele, haplotype analysis supporting a founder effect for unstable alleles and comparative analysis of SCA17 genotypes

BACKGROUND: Spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder in man, is caused by an expanded polymorphic polyglutamine-encoding trinucleotide repeat in the gene for TATA-box binding protein (TBP), a main transcription factor. Observed pathogenic expansions ranged from 43 – 63 glutamine (Gln) codons (Gln(43–63)). Reduced penetrance is known for Gln(43–48 )alleles. In the vast majority of families with SCA17 an expanded CAG repeat interrupted by a CAA CAG CAA element is inherited stably. RESULTS: Here, we report the first pedigree with a Gln(49 )allele that is a) not interrupted, b) unstable upon transmission, and c) associated with reduced penetrance or very late age of onset. The 76-year-old father of two SCA17 patients carries the Gln(49 )TBP allele but presents without obvious neurological symptoms. His children with Gln(53 )and Gln(52 )developed ataxia at the age of 41 and 50. Haplotype analysis of this and a second family both with uninterrupted expanded and unstable pathological SCA17 alleles revealed a common core genotype not present in the interrupted expansion of an unrelated SCA17 patient. Review of the literature did not present instability in SCA17 families with expanded alleles interrupted by the CAA CAG CAA element. CONCLUSION: The presence of a Gln(49 )SCA17 allele in an asymptomatic 76-year-old male reams the discussion of reduced penetrance and genotypes producing very late disease onset. In SCA17, uninterrupted expanded alleles of TBP are associated with repeat instability and a common founder haplotype. This suggests for uninterrupted expanded alleles a mutation mechanism and some clinical genetic features distinct from those alleles interrupted by a CAA CAG CAA element

Towards the development of ecosystem-based indicators of mangroves functioning state in the context of the EU water framework directive

European Water Framework Directive is enforced in five tropical French Oversea Territories where mangroves are present. Developing bioindication tools to support the ecosystem-based management approach of the Directive is needed. A series of expert workshops was organized and led to the proposal of a strategy and of an applied research program to develop bioindication tools. The proceedings of the workshops are presented as a case study, as this is the first time such an integrative ecosystem-based approach is proposed in mangroves, combining structural and functional aspects, from forest structure to benthic community functioning

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

What Could Be the Role of Antifungal Lock-Solutions? From Bench to Bedside

Candidemia related to the presence of a biofilm are often reported in patients with vascular catheters. Once they are mature, biofilms are persistent infectious reservoirs, and the yeasts dispersed from biofilms can cause infections. Sessile yeasts typically display increased levels of resistance to most antimicrobial agents and systemic treatments usually fail to eradicate previously formed fungal biofilms. In a curative strategy, antifungal lock therapy may help to sterilize catheters, with very high concentrations of antifungal agents, which are not compatible with systemic use. This strategy has been studied by several authors in in vitro and in vivo studies, and more rarely, in clinical settings for adult and paediatric patients. Our study aims to assess the efficacy of the antifungal solutions used for lock therapy and demonstrated by the different teams

Candida species, salive et candidoses oro-pharyngées

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Biofilm, lentilles de contact et infections cornéennes

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Etude de l'effet in vitro de deux échinocandines sur la croissance de biofilms de candida albicans en phases intermédiaire et de maturation

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF