Synthèse stéréosélective d'éthers d'énol acycliques substitués et exocycliques fonctionnalisés

Les éthers d'énol fonctionnalisés sont des molécules importantes, ayant plusieurs applications comme intermédiaires en chimie organique. Ils peuvent participer à des réactions de Diels-Alder, des réactions de Mukakaima, etc. Parmi cette famille de composés, les α-iodoéthers d'énol sont particulièrement intéressants, car en plus des applications précédentes, ils sont des précurseurs des anions acyles, synthons forts utiles en synthèse organique. Toutefois, il existe peu de méthodes pour préparer les α-iodoéthers d'énol. Le laboratoire du professeur Daoust a montré que l'addition radicalaire d'halogénoalcanes activés XCH₂Z (X=I, Br; Z=CO₂Et, CONH₂, CN) sur les éthers d'ynols permet de produire, de façon spécifique et sous des conditions douces, les \ud α-iodoéthers d'énol. Cependant, une étude exhaustive de l'effet de l'encombrement stérique sur la réactivité et la stéréosélectivité de la réaction radicalaire n'a pas encore été effectuée. Dans le cadre de ce projet, on s'intéresse à évaluer et analyser l'effet de l'encombrement stérique des éthers d'ynol sur la réaction d'addition radicalaire intermoléculaire. La version intramoléculaire de cette méthodologie, qui n'avait pas encore été étudiée, est aussi développée et évaluée. Ainsi, on vous rapporte dans le présent travail la mise au point d'une méthode simple et efficace pour préparer les éthers d'énol exocycliques fonctionnalisés avec de bons rendements à partir d'éther d'ynol iodé et de n-BuLi à basse température. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Radicaux, Éthers d'ynol, Éthers d'énol acycliques, Halogénoéthers d'ynol, Addition anionique, Éthers d'énol cycliques

The protein C deficiency and its effects on in-vitro fertilization outcome and recurrent pregnancy loss: a Syrian cohort study

Background: Protein C deficiency is a rare disease; it could be primary or secondary. Female patients with protein C deficiency may develop pregnancy-associated thrombosis. The clear association between the protein C deficiency and fertility or in-vitro fertilization (IVF) results has not been known yet. In our study, we aimed to determine the prevalence of protein C deficiency in Syrian infertile women and to assess the impact of protein C deficiency on abortion, recurrent IVF Failure, and IVF results.Methods: the electronic patients’ results were retrospectively screened. A total of 238 women, who had IVF cycles between January 2012 and December 2017 in a tertiary care hospital, met our including criteria.Results: the prevalence of protein C deficiency was 13.45%. There was a significant association between the protein C level and recurrent pregnancy loss (RPL). Furthermore, the protein C deficiency has an impact on the IVF results. Additionally, we did not find any association between protein C deficiency and age or number of previous IVF cycles.Conclusions: the protein C could be the hidden factor that affects IVF results. More research should be done to better understanding the role of protein C in infertility and IVF

Hospitalization of Children with Down Syndrome

INTRODUCTION: Children with Down syndrome present with multiple medical problems in a higher prevalence compared with the general population, which may lead to hospitalizations. METHODS: Analysis of 560 hospitalizations of 162 children aged 0-16 years with Down syndrome at Hadassah Medical Center during the years 1988-2007 compared with data on children in the general population, hospitalized at the same period. Data was collected from patient files and statistical data from the Ministry of Health. RESULTS: Respiratory infections were the leading cause for hospitalization of children with Down syndrome. The number of hospitalizations of children with Down syndrome compared to the number of all children, who were hospitalized was surprisingly similar to their proportion in the general population. Eleven children died during their hospitalization (five heart failure, three sepsis, one respiratory tract infection, and one due to complication after surgery). Nine of the 11 had a congenital heart anomaly. CONCLUSION: Children with Down syndrome can present with complex medical issues and we support the concept of a multidisciplinary team that has experience and knowledge to serve as a one stop shop for these individuals and their families, with timely visits in which a comprehensive evaluation is performed, problems attended to and prevention plans applied. In this way, we may prevent morbidity, hospitalizations, and mortality

Corneal Perforation after Nd:YAG Capsulotomy: A Case Report and Literature Review

Background: Nd:YAG capsulotomy is the treatment of choice for posterior capsular opacification after cataract surgery. We report a case of corneal perforation following Nd:YAG capsulotomy in a patient with systemic scleroderma. Case Presentation: A 69-year-old woman presented with acute onset of blurred vision 2 weeks following Nd:YAG laser capsulotomy for posterior subcapsular opacification. On examination, her best-corrected visual acuity was 1/120, and bio-microscopy revealed a central full-thickness corneal laceration. Conservative treatment consisted of topical ocular antibiotics, cycloplegics, hypotensive drops and a soft therapeutic contact lens. Her final visual acuity improved to 6/18 with resolution of the corneal laceration. Conclusion: The possibility of corneal perforation after Nd-YAG capsulotomy in patients with systemic scleroderma and connective tissue disease should be borne in mind when treating such patients

Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial

Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis

TRIO gene segregation in a family with cerebellar ataxia

Aim of the study: To report a family with a novel TRIO gene mutation associated withphenotype of cerebellar ataxia. Materials and methods: Seven family members of Caribbean descent were recruited through our ataxia research protocol; of the family members, the mother and all 3 children were found to be affected with severe young-onset and rapidly progressive truncal and appendicular ataxia leading to early disability. Array comparative genomic hybridization, mitochondrial DNA analysis, and whole-exome sequencing were performed on 3 of the family members (mother and 2 daughters). Results: While the maternal grandmother, great uncle and great aunt were unaffected, the mother and 3 children displayed cognitive dysfunction, severe ataxia, spasticity, and speech disturbances. Age of onset ranged between 3 and 17 years, with average current disease duration of 21 years. Whole-exome sequencing showed a variant p.A1214V in exon 22 of the TRIO gene in 3 of the family members. Array comparative genomic hybridization and mitochondrial DNA analysis were normal. The same variant was later discovered in all but one family member. Conclusions and clinical implications: The TRIO p.A1214V variant is associated with cerebellar ataxia in the studied family; it was present in all affected and unaffected family members. Phenotype is severe and broad. Anticipation seems to be present (based on 2 affected generations). It is warranted to screen additional familial early-onset and rapidly progressive ataxia cases for this genotype. TRIO gene mutations may well represent a novel spinocerebellar ataxia subtype

First families with spinocerebellar ataxia type 7 in Poland

Introduction. We present the first two Polish families diagnosed with spinocerebellar ataxia type 7 (SCA7) and draw attention to cardiac involvement as a new potential manifestation of this disease. Material and methods. Two well-documented kindreds are presented. Results. The proband from Family 1 presented aged 54 years with vision worsening followed by progressive imbalance. Brain MRI demonstrated cerebellar atrophy. Genetic testing confirmed CAG repeat expansion (42/10) in ATXN7 gene. The proband from Family 2 developed imbalance at age 20, followed by progressive deterioration of vision. Brain MRI revealed cerebellar atrophy. Additionally, she developed chronic congestive heart failure and, at age 38, had cardiomyopathy with an ejection fraction of 20% and significant mitral and tricuspid regurgitation. Genetic analysis found abnormal CAG expansion in the ATXN7 (46/10). Conclusions and clinical implications. Vision loss due to pigmentary retinal degeneration is the distinguishing feature of SCA7 and often the initial manifestation. Although SCA7 is one of the most common SCAs in Sweden, it has never been reported in neighbouring Poland. Until now, cardiac abnormalities have only been described in infantile-onset SCA7 with large CAG repeats. The observed cardiac involvement in Family 2 may be coincidental, albeit a new possible manifestation of SCA7 cannot be excluded

Small RNA-mediated regulation of iPS cell generation

The generation of induced pluripotent stem cells is limited by the low reprogramming efficiency of somatic cells. Here, three clusters of miRNAs are shown to enhance reprogramming efficiency by targeting the TGF-β and p53 pathways, which inhibit the process