Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

The mexican war : a history of its origen, and a detailed account of the victories wich terminated in the surrender of the capital ; with the official despatches of the generals. To which is added, the Treaty of Peace, and valuable tables of the strength and losses of the United States Army.

UANL

History of south America and Mexico ; comprising their discouvery geography, politics, commerce and revolutions

UANL

Winchester School of Art PhD and MPhil applications guide

This document specifies the guidelines for all applications, recommending a well-structured 5-10 page proposal detailing the significance and relevance of the proposal, and how it fits into existing work. Candidates should note that we need to be sure we have expertise in the research area, and that the application process will normally require up to four weeks of referral to potential supervisors.

Lifestyle and health status in a sample of Swedish women four years after pregnancy : a comparison of women with a history of normal pregnancy and women with a history of gestational diabetes mellitus

Background: Despite the recommendations to continue the regime of healthy food and physical activity (PA) postpartum for women with previous gestational diabetes mellitus (GDM), the scientific evidence reveals that these recommendations may not be complied to. This study compared lifestyle and health status in women whose pregnancy was complicated by GDM with women who had a normal pregnancy and delivery. Methods: The inclusion criteria were women with GDM (ICD-10: O24.4 A and O24.4B) and women with uncomplicated pregnancy and delivery in 2005 (ICD-10: O80.0). A random sample of women fulfilling the criteria (n = 882) were identified from the Swedish Medical Birth Register. A questionnaire was sent by mail to eligible women approximately four years after the pregnancy. A total of 444 women (50.8%) agreed to participate, 111 diagnosed with GDM in their pregnancy and 333 with normal pregnancy/ delivery. Results: Women with previous GDM were significantly older, reported higher body weight and less PA before the index pregnancy. No major differences between the groups were noticed regarding lifestyle at the follow-up. Overall, few participants fulfilled the national recommendations of PA and diet. At the follow-up, 19 participants had developed diabetes, all with previous GDM. Women with previous GDM reported significantly poorer self-rated health (SRH), higher level of sick-leave and more often using medication on regular basis. However, a history of GDM or having overt diabetes mellitus showed no association with poorer SRH in the multivariate analysis. Irregular eating habits, no regular PA, overweight/obesity, and regular use of medication were associated with poorer SRH in all participants. Conclusions: Suboptimal levels of PA, and fruit and vegetable consumption were found in a sample of women with a history of GDM as well as for women with normal pregnancy approximately four years after index pregnancy. Women with previous GDM seem to increase their PA after childbirth, but still they perform their PA at lower intensity than women with a history of normal pregnancy. Having GDM at index pregnancy or being diagnosed with overt diabetes mellitus at follow-up did not demonstrate associations with poorer SRH four years after delivery.

Notes on the Colloquium of the Association of Caribbean Historians on "Political Ideas and Tendencies in the History of the Caribbean" and "Cities in the Caribbean"

Comentarios sobre el 8o Coloquio de la Asociacion de Historiadores Caribenos en el que se analizo las ideas politicas y las ciudades en la historia del Caribe

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.