Análisis de las actividades de evaluación enmarcadas en el método ABP

El grado de Medicina de la UdG nació integrando el Aprendizaje Basado en Problemas. En este método centrado en el estudiante, la evaluación es parte del aprendizaje y debe ser coherente con el método y los resultados de aprendizaje para potenciar la profundización de lo aprendido. En este estudio se han analizado las actividades de evaluación, estudiando el alineamiento con los resultados de aprendizaje y el método. Los resultados evidencian que los resultados de aprendizaje reflejan una demanda cognitiva baja, las actividades de evaluación, en gran parte alinean con el método, y se observa una coherencia entre las distintas actividades de evaluación. El estudio sugiere mejorar aspectos de los resultados de aprendizaje y de la evaluación y pretende potenciar la evaluación de la práctica docente para seguir avanzando en la facilitación del aprendizaje de los estudiantes

A Novel Missense Mutation, I890T, in the Pore Region of Cardiac Sodium Channel Causes Brugada Syndrome

Brugada syndrome (BrS) is a life-threatening, inherited arrhythmogenic syndrome associated with autosomal dominant mutations in SCN5A, the gene encoding the cardiac Na+ channel alpha subunit (Nav1.5). The aim of this work was to characterize the functional alterations caused by a novel SCN5A mutation, I890T, and thus establish whether this mutation is associated with BrS. The mutation was identified by direct sequencing of SCN5A from the proband's DNA. Wild-type (WT) or I890T Nav1.5 channels were heterologously expressed in human embryonic kidney cells. Sodium currents were studied using standard whole cell patch-clamp protocols and immunodetection experiments were performed using an antibody against human Nav1.5 channel. A marked decrease in current density was observed in cells expressing the I890T channel (from -52.0±6.5 pA/pF, n = 15 to -35.9±3.4 pA/pF, n = 22, at -20 mV, WT and I890T, respectively). Moreover, a positive shift of the activation curve was identified (V1/2 = -32.0±0.3 mV, n = 18, and -27.3±0.3 mV, n = 22, WT and I890T, respectively). No changes between WT and I890T currents were observed in steady-state inactivation, time course of inactivation, slow inactivation or recovery from inactivation parameters. Cell surface protein biotinylation analyses confirmed that Nav1.5 channel membrane expression levels were similar in WT and I890T cells. In summary, our data reveal that the I890T mutation, located within the pore of Nav1.5, causes an evident loss-of-function of the channel. Thus, the BrS phenotype observed in the proband is most likely due to this mutation. © 2013 Tarradas et al

Community-acquired methicillin-resistant Staphylococcus aureus: what do we need to know?

AbstractCommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a matter of concern worldwide, in particular in the USA. For the analysis of emergence and spread, clear definitions based on epidemiological origin are needed for discrimination between CA-MRSA, healthcare-associated community MRSA, and healthcare-associated MRSA (HA-MRSA). Although its role in pathogenesis is currently under debate, the capability for Panton–Valentine leukocidin formation is associated with the majority of CA-MRSA isolates from North America and from Europe. Most CA-MRSA isolates are attributed to clonal lineages different from HA-MRSA; there are, however, clonal lineages from which both HA-MRSA and CA-MRSA have been reported (e.g. ST1, ST5, ST8, and ST22); CA-MRSA ST8 (USA300), which is most frequent in the USA, has meanwhile been reported from Europe. CA-MRSA ST80 is widely disseminated in Europe; because of its pronounced oxacillin heteroresistance phenotype, cefoxitin-based assays are advisable for reliable detection. So far, CA-MRSA infections seem to be much less frequent in Europe than in the USA, where patients with particular predispositions and low social status are at especial risk

Large Genomic Imbalances in Brugada Syndrome

Purpose Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. Methods 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). Results The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. Conclusion CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes

El paper de les subunitats beta en la regulació del canal de sodi cardíac associat a la mort sobtada

Les Síndromes de QT Llarg (SQTL) i de Brugada (SBr) són malalties hereditàries amb un alt risc de mort sobtada cardíaca degut a alteracions elèctriques cardíaques sense cap defecte estructural del cor. Estan relacionades amb mutacions a gens que codifiquen pels canals iònics cardíacs o proteïnes reguladores. No obstant això, resten sense diagnòstic genètic un percentatge elevat de pacients amb SQTL (20-35%) i SBr (60-75%) després de la sequenciació dels gens relacionats. En aquesta tesi es planteja si mutacions a les subunitats β del canal de sodi no associades prèviament a SQTL i SBr poden ser responsables d’aquestes malalties en els pacients sense mutació. Els resultats obtinguts relacionen per primera vegada mutacions als gens SCN1Bb i SCN2B a la SQTL i SBr, respectivament; i aporten noves evidències de les bases genètiques d’aquestes malalties i del paper fonamental de les subunitats β en la funció del canal de sodi cardíac.Long QT Syndrome (LQTS) and Brugada Syndrome (BrS) are inheritable cardiac diseases with a high risk of sudden cardiac death due to electric alterations without structural defects of the heart. These alterations are determined by mutations in cardiac ion channels or regulatory proteins. However, near 20-35% of LQTS patients and 60-75% of BrS patients remain without a genetic diagnosis after the screening of LQTS and BrS-previously related genes. Our assumption was that mutations in the sodium channel β subunits, still not related to the respective disease, could explain the phenotype in patients without a mutation after genetic screening. We identify for the first time mutations in two β subunits genes (SCN1Bb and SCN2B) responsible for LQTS and BrS, respectively; and our studies provide new evidences of the genetic basis of LQTS and BrS, and support the growing evidence of the important role of β subunits on cardiac sodium channel function

El paper de les subunitats beta en la regulació del canal de sodi cardíac associat a la mort sobtada

Les Síndromes de QT Llarg (SQTL) i de Brugada (SBr) són malalties hereditàries amb un alt risc de mort sobtada cardíaca degut a alteracions elèctriques cardíaques sense cap defecte estructural del cor. Estan relacionades amb mutacions a gens que codifiquen pels canals iònics cardíacs o proteïnes reguladores. No obstant això, resten sense diagnòstic genètic un percentatge elevat de pacients amb SQTL (20-35%) i SBr (60-75%) després de la sequenciació dels gens relacionats. En aquesta tesi es planteja si mutacions a les subunitats β del canal de sodi no associades prèviament a SQTL i SBr poden ser responsables d’aquestes malalties en els pacients sense mutació. Els resultats obtinguts relacionen per primera vegada mutacions als gens SCN1Bb i SCN2B a la SQTL i SBr, respectivament; i aporten noves evidències de les bases genètiques d’aquestes malalties i del paper fonamental de les subunitats β en la funció del canal de sodi cardíac.Long QT Syndrome (LQTS) and Brugada Syndrome (BrS) are inheritable cardiac diseases with a high risk of sudden cardiac death due to electric alterations without structural defects of the heart. These alterations are determined by mutations in cardiac ion channels or regulatory proteins. However, near 20-35% of LQTS patients and 60-75% of BrS patients remain without a genetic diagnosis after the screening of LQTS and BrS-previously related genes. Our assumption was that mutations in the sodium channel β subunits, still not related to the respective disease, could explain the phenotype in patients without a mutation after genetic screening. We identify for the first time mutations in two β subunits genes (SCN1Bb and SCN2B) responsible for LQTS and BrS, respectively; and our studies provide new evidences of the genetic basis of LQTS and BrS, and support the growing evidence of the important role of β subunits on cardiac sodium channel function

Análisis de las actividades de evaluación enmarcadas en el método ABP

El grado de Medicina de la UdG nació integrando el Aprendizaje Basado en Problemas. En este método centrado en el estudiante, la evaluación es parte del aprendizaje y debe ser coherente con el método y los resultados de aprendizaje para potenciar la profundización de lo aprendido. En este estudio se han analizado las actividades de evaluación, estudiando el alineamiento con los resultados de aprendizaje y el método. Los resultados evidencian que los resultados de aprendizaje reflejan una demanda cognitiva baja, las actividades de evaluación, en gran parte alinean con el método, y se observa una coherencia entre las distintas actividades de evaluación. El estudio sugiere mejorar aspectos de los resultados de aprendizaje y de la evaluación y pretende potenciar la evaluación de la práctica docente para seguir avanzando en la facilitación del aprendizaje de los estudiante

Análisis de las actividades de evaluación enmarcadas en el método ABP

El grado de Medicina de la UdG nació integrando el Aprendizaje Basado en Problemas. En este método centrado en el estudiante, la evaluación es parte del aprendizaje y debe ser coherente con el método y los resultados de aprendizaje para potenciar la profundización de lo aprendido. En este estudio se han analizado las actividades de evaluación, estudiando el alineamiento con los resultados de aprendizaje y el método. Los resultados evidencian que los resultados de aprendizaje reflejan una demanda cognitiva baja, las actividades de evaluación, en gran parte alinean con el método, y se observa una coherencia entre las distintas actividades de evaluación. El estudio sugiere mejorar aspectos de los resultados de aprendizaje y de la evaluación y pretende potenciar la evaluación de la práctica docente para seguir avanzando en la facilitación del aprendizaje de los estudiantes

Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death

A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death