Bioinformática: base de datos de matrices de expresión génica para su análisis vía web

El IBB ha desarrollado un servidor de aplicaciones: http://revolutionresearch.uab.es para el análisis de microarrays. Estas microarrays las obtienen y las suben a la base de datos local los usuarios de la aplicación. En la presente memoria se detalla el proceso realizado para automatizar la subida de microarrays públicas a la base de datos local. Estas microarrays se obtendrán del NCBI. El proceso de descarga de microarrays se realizará cada dos meses y estará sincronizado con un proceso de descarga de genes marcadores de microarrays del NCBI. En la memoria también se describen las fases realizadas para crear la interfaz web para gestionar estas microarrays públicas y las modificaciones realizadas sobre el aplicativo web para permitir realizar análisis con estas microarrays.

Estudi per la implantació d'un ERP en una oficina de farmàcia

En aquest projecte es realitza l'estudi previ de la implantació d'un Planificador de Recursos Empresarials (ERP) en una oficina de farmàcia. Es pretenen analitzar els diferents punts a tenir en compte, tant de l'empresa com del ERP, a l'hora d'escollir el millor sistema per implantar a la farmàcia. Primerament hi ha una part teòrica on es defineix el concepte de ERP, donant una visió del mercat actual i del què suposa implantar un ERP en una empresa. El segon pas és el més rellevant, es tracta de l'anàlisi dels requeriments funcionals i tècnics de la farmàcia. Finalment, es proposen els 3 sistemes més ben col·locats per a una possible implantació i s'escull el que millor s'adapta a les necessitats especificades.

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Compuesto por tres partes principales (el análisis, el diseño y la implementación), con este proyecto pretendo desarrollar una aplicación web que permita un intercambio de peticiones y/o mensajes entre diferentes usuarios de un mismo grupo.

Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS.Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers.Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients.Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL

Background: Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA) and total number of piglets born (TNB) in a three generation Iberian by Meishan F2 intercross. Results: The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P < 0.001) and SSC17 (P < 0.01) with effects on both traits. This relative paucity of significant results contrasted very strongly with the wide array of highly significant epistatic QTL that emerged in the bi-dimensional genome-wide scan analysis. As much as 18 epistatic QTL were found for NBA (four at P < 0.01 and five at P < 0.05) and TNB (three at P < 0.01 and six at P < 0.05), respectively. These epistatic QTL were distributed in multiple genomic regions, which covered 13 of the 18 pig autosomes, and they had small individual effects that ranged between 3 to 4% of the phenotypic variance. Different patterns of interactions (a × a, a × d, d × a and d × d) were found amongst the epistatic QTL pairs identified in the current work.Conclusions: The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17), dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.

A protocol describing the genetic correction of somatic human cells and subsequent generation of IPS cell

The generation of patient-specific induced pluripotent stem cells (iPSCPSCPSCs) offers unprecedented opportunities for modeling and treating human disease. In combination with gene therapy, the iPSCPSCPSC technology can be used to generate disease-free progenitor cells of potential interest for autologous cell therapy. We explain a protocol for the reproducible generation of genetically corrected iPSCPSCPSCs starting from the skin biopsies of Fanconi anemia patients using retroviral transduction with OCT4, SOX2 and KLF4. Before reprogramming, the fibroblasts and/or keratinocytes of the patients are genetically corrected with lentiviruses expressing FANCA. The same approach may be used for other diseases susceptible to gene therapy correction. Genetically corrected, characterized lines of patient-specific iPSCPSCPSCs can be obtained in 4–5 months.

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Background: Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results: Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion:This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.

Biomechanical wall properties of human intracranial aneurysms resected following surgical clipping (IRRAs Project)

Background and purpose: Individual rupture risk assessment of intracranial aneurysms is a major issue in the clinical management of asymptomatic aneurysms. Aneurysm rupture occurs when wall tension exceeds the strength limit of the wall tissue. At present, aneurysmal wall mechanics are poorly understood and thus, risk assessment involving mechanical properties is inexistent. Aneurysm computational hemodynamics studies make the assumption of rigid walls, an arguable simplification. We therefore aim to assess mechanical properties of ruptured and unruptured intracranial aneurysms in order to provide the foundation for future patient-specific aneurysmal risk assessment. This work also challenges some of the currently held hypotheses in computational flow hemodynamics research. Methods: A specific conservation protocol was applied to aneurysmal tissues following clipping and resection in order to preserve their mechanical properties. Sixteen intracranial aneurysms (11 female, 5 male) underwent mechanical uniaxial stress tests under physiological conditions, temperature, and saline isotonic solution. These represented 11 unruptured and 5 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a 3-parameter (C(10), C(01), C(11)) Mooney-Rivlin hyperelastic model. Each aneurysm was classified according to its biomechanical properties and (un)rupture status.Results: Tissue testing demonstrated three main tissue classes: Soft, Rigid, and Intermediate. All unruptured aneurysms presented a more Rigid tissue than ruptured or pre-ruptured aneurysms within each gender subgroup. Wall thickness was not correlated to aneurysmal status (ruptured/unruptured). An Intermediate subgroup of unruptured aneurysms with softer tissue characteristic was identified and correlated with multiple documented risk factors of rupture. Conclusion: There is a significant modification in biomechanical properties between ruptured aneurysm, presenting a soft tissue and unruptured aneurysms, presenting a rigid material. This finding strongly supports the idea that a biomechanical risk factor based assessment should be utilized in the to improve the therapeutic decision making.

Towards reusability and tailorability in collaborative learning systems using IMS-LD and grid services

CSCL applications are complex distributed systems that posespecial requirements towards achieving success in educationalsettings. Flexible and efficient design of collaborative activitiesby educators is a key precondition in order to provide CSCL tailorable systems, capable of adapting to the needs of eachparticular learning environment. Furthermore, some parts ofthose CSCL systems should be reused as often as possible inorder to reduce development costs. In addition, it may be necessary to employ special hardware devices, computational resources that reside in other organizations, or even exceed thepossibilities of one specific organization. Therefore, theproposal of this paper is twofold: collecting collaborativelearning designs (scripting) provided by educators, based onwell-known best practices (collaborative learning flow patterns) in a standard way (IMS-LD) in order to guide the tailoring of CSCL systems by selecting and integrating reusable CSCL software units; and, implementing those units in the form of grid services offered by third party providers. More specifically, this paper outlines a grid-based CSCL system having these features and illustrates its potential scope and applicability by means of a sample collaborative learning scenario.

Free-and open source software for a course on network management: authoring and enactment of scripts based on collaborative learning strategies

This paper describes a Computer-Supported Collaborative Learning (CSCL) case study in engineering education carried out within the context of a network management course. The case study shows that the use of two computing tools developed by the authors and based on Free- and Open-Source Software (FOSS) provide significant educational benefits over traditional engineering pedagogical approaches in terms of both concepts and engineering competencies acquisition. First, the Collage authoring tool guides and supports the course teacher in the process of authoring computer-interpretable representations (using the IMS Learning Design standard notation) of effective collaborative pedagogical designs. Besides, the Gridcole system supports the enactment of that design by guiding the students throughout the prescribed sequence of learning activities. The paper introduces the goals and context of the case study, elaborates onhow Collage and Gridcole were employed, describes the applied evaluation methodology, anddiscusses the most significant findings derived from the case study.

Exhaled breath condensate (EBC) as a matrix for nanoparticle exposure and health effect evaluation : final scientific report

The aim of this pilot project was to evaluate the feasibility of assessing the deposited particle dose in the lungs by applying the dynamic light scattering-based methodology in exhaled breath condensateur (EBC). In parallel, we developed and validated two analytical methods allowing the determination of inflammatory (hydrogen peroxide - H2O2) and lipoperoxidation (malondialdehyde - MDA) biomarkers in exhaled breath condensate. Finally, these methods were used to assess the particle dose and consecutive inflammatory effect in healthy nonsmoker subjects exposed to environmental tobacco smoke in controlled situations was done.

La Renovación de la atención primaria desde la consulta

Texto y contexto que responden claramente al título bajo la batuta dedos médicos de familia, Josep Casajuana y Juan Gérvas, que aman suprofesión pero que, sobre todo, llevan décadas impulsando iniciativasclínicas, gestoras y de investigación para mejorar la atención a lospacientes. De ellos (y Mercedes Pérez) son los dos capítulos inicialesque sitúan el tema: qué cambios pueden impulsar los profesionalespara recuperar el protagonismo y liberarse de ataduras y complejos ycómo, de manera muy práctica, se combina ciencia y tecnología paraobtener lo mejor de los valores y tiempo del profesional comprometido.Para acabar de tener consciencia de la situación y organización de laatención primaria en España, analizan en los dos capítulos siguientes(junto con Marc Casajuana y Roberto Sánchez) qué supone ser médicode familia en Europa y cómo en un día cualquiera se resuelven hasta17 problemas distintos de atención y seguimiento.El contexto de la consulta –en la segunda mitad del libro– plantea larenovación como exigencia social aportando investigación originalsobre: 1) cómo lo que vamos aprendiendo acerca de la elección deespecialidad médica puede ayudar a refundar la Medicina de Familia yComunitaria (Patricia Barber y Beatriz González); 2) las formas dereasignar recursos (Francisco Hernansanz); 3) cómo renovar los servicios sanitarios en su conjunto en época de crisis (Vicente Ortún y MaríaCallejón); y 4) un panorama muy documentado sobre los campos demanifiesta necesidad de mejora en atención primaria (Ricard Meneu ySalvador Peiró),cuyo abordaje da sentido y complementa la renovaciónplanteada en la primera parte del libro.

Ulceración rectal como una complicación del uso de sistema de control fecal Fexi-Seal: relato de casos

El Sistema Fexi-Seal es un dispositivo desarrollado para proporcionar mejores cuidados a los pacientes críticos con incontinencia fecal. Existen trabajos que demuestran la seguridad y eficacia del dispositivo, siendo escasos los relatos relacionados con eventos adversos. El presente artículo presenta dos casos de pacientes críticos portadores de Fexi-Seal que desarrollaron complicaciones con su uso. El sistema se mostró eficaz para el tratamiento, sin embargo, es necesaria atención especial en su manejo, particularmente en cuanto al alivio periódico de la presión de la ampolla rectal y al posicionamiento correcto de la bolsa colectora en la cama para evitar tracción excesiva. El Sistema Flexi-Seal permite manejar adecuadamente la diarrea en pacientes críticos, mejorando su bienestar y disminuyendo las complicaciones asociadas a ella, aunque se torna necesario aumentar el conocimiento sobre las complicaciones relacionadas con su empleo.