Sandhoff disease is a severe inherited neurodegenerative disorder resulting from deficiency of the b-subunit of hexosaminidases A and B, lysosomal hydrolases involved in the degradation of G M2 ganglioside and related metabolites. Currently, there is no viable treatment for the disease. Here, we show that adenovirus-mediated transfer of the bsubunit of b-hexosaminidase restored Hex A and Hex B activity after infection of Sandhoff fibroblasts. Gene transfer following intracerebral injection in a murine model of Sandhoff disease resulted in near-normal level of enzymatic activity in the entire brain at the different doses tested. The addition of hyperosmotic concentrations of mannitol to the adenoviral vector resulted in an enhancement of vector diffusion in the injected hemisphere. Adenoviral-induced lesions were found in brains injected with a high dose of the vector, but were not detected in brains injected with 100-fold lower doses, even in the presence of mannitol. Our data underline the advantage of the adjunction of mannitol to low doses of the adenoviral vector, allowing a high and diffuse transduction efficiency without viral cytotoxicity.
Gaucher disease (GD) is an inherited glycolipid storage disorder resulting from the deficiency of glucocerebrosidase. It is the most frequent lysosomal storage disease in Romania, accounting for 70% of all lysosomal disorders diagnosed since 1997 in this country. The prevalence of six common mutations (N370S, L444P, R463C, 84GG, recNciI and recTL) and their phenotypic impact were studied in 20 type 1 GD patients of non-Jewish origin. Mutation analysis identified 77.8% of the GD alleles. The N370S mutation had the highest prevalence (50%), followed by the L444P (22.2%) and the recNciI (5.6%) alleles. Mutations R463C, 84GG and recTL have not been found in our patients. Rare or novel mutations likely accounted for 22.2% of the disease-producing uncharacterised alleles. Our study indicates a high prevalence of type 1 among Romanian GD patients. Clinical phenotype and disease severity were evaluated according to the standardised severity score index. Genotype -phenotype correlations were similar to those reported for other Caucasian non-Jewish populations. The absence of neuronopathic disease in patients presenting at least one copy of the N370S allele was confirmed, but the relative mildness of N370S homozygotes was not a constant feature among our patients. The presence of the L444P or of uncharacterised sporadic mutations was always associated with severe clinical manifestations, even in compound heterozygotes with the N370S allele. A large degree of phenotypic variability was observed in patients displaying the same genotype. The particularities of genotype -phenotype correlations may suggest the impact of other genetic or non-genetic factors on the clinical picture.
Abstract:The evolution of Internet from static Web "publishing" to the highly participative, and data-driven, innovations of Web 2.0 has been influencing how people search for health-related information. This review included studies indexed in the PubMed electronic database that focused on social media analysis, examining relationships between participants (patients and healthcare consumers) through social media usage. The obtained results showed that previous research regarding social media's impact on patients and healthcare consumers aimed at a combination of platforms, but there is a penury of information about niche topics or its usage for retrieving medical information. Nevertheless, social media proved to be to be a promising tool in research mainly for recruitment purposes. The review has outlined that eHealth literacy is an attribute for populations that are female and relatively young and educated. Blogs share personal experiences, YouTube contains unregulated, high-and low-quality information that can mislead individuals, Facebook contains more marketing than health-related information, while Wikipedia is recommended for providing high-quality information. Despite healthcare practitioners' and healthcare public institutions' reluctance about the use of social media, this review demonstrates the usefulness of social media for patients and healthcare consumers in retrieving health-related information based on content availability and usage implications, and highlights gaps in knowledge that further research needs to fill.
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