Comprehensive analysis of RET common and rare variant patientsin a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events

Background. RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. In the present study, we have performed a comprehensive study of our HSCR series evaluating the involvement of both RET rare variants (RVs) and common variants (CVs) in the context of the disease. Methods. RET mutational screening was performed by dHPLC and direct sequencing for the identification of RVs. In addition Taqman technology was applied for the genotyping of 3 RET CVs previously associated to HSCR, including a variant lying in an enhancer domain within RET intron 1 (rs2435357). Statistical analyses were performed using the SPSS v.17.0 to analyze the distribution of the variants. Results. Our results confirm the strongest association to HSCR for the "enhancer" variant, and demonstrate a significantly higher impact of it in male versus female patients. Integration of the RET RVs and CVs analysis showed that in 91.66% of cases with both kinds of mutational events, the enhancer allele is in trans with the allele bearing the RET RV. Conclusions. A gender effect exists on both the transmission and distribution of rare coding and common HSCR causing mutations. In addition, these RET CVs and RVs seem to act in a synergistic way leading to HSCR phenotype.

Negotiation Techniques in a Digital Library

The Andalusian eHealth Library (Biblioteca Virtual del Sistema Sanitario Público de Andalucía, BV-SSPA), created in June 2006 as a strategic action of the Andalusian Government with the aim of becoming the engine for the knowledge management of the health system in the region, has meant a radical change of mind in the way libraries can be managed: - As a regional library, it coordinates the 42 document library centers of the hospital network. - It is an organization in charge of its own budget and management. - It is the only intermediary for contracting health science resources. These factors have empowered the library in its dealings with other organizations such as stakeholders, suppliers, universities, etc. The centralization of the purchasing and the librarian network has made this library strong enough to deal with the economic recession and budgetary problems.