Estructura factorial y consistencia interna de la Escala de Severidad de Fatiga en población colombiana con enfermedades crónicas

El presente estudio de corte psicométrico, tuvo como objetivo analizar la estructura factorial y la consistencia interna versión en español del cuestionario Fatigue Severity Scale (FSS) en población colombiana de enfermos crónicos. Para ello se aplicó el cuestionario a 52 enfermos crónicos de la ciudad de Villavicencio. El análisis factorial denota tres factores: el factor 1 denominado como afectación física, el factor 2 denominado afectación social y finalmente el factor 3 denominado afectación motivacional de la fatiga, que explican el 76,324% de la varianza total acumulada, y un alfa de Cronbach de 870. Los resultados muestran una alta confiabilidad y concordancia en la estructura factorial con la versión original, lo que implica adecuada validez de la prueba en población colombiana de enfermos crónicos.The present study has a psychometric design, with the objective of analyzing the factorial structure and the internal consistency for the Spanish version of the Fatigue Severity Scale (FSS) Questionnaire for Colombian population with chronic disease. Was applied the questionnaire to 52 people with chronic disease in Villavicencio city. The factorial Analysis indicates three factors: Factor 1 named physical affectation, Factor 2 named social affectation and Factor 3 named motivational affectation of the fatigue, where they explain the 76.324% of the total cumulative variance with .870 of Cronbach's Alpha. The results present a high reliability and concordance for the factorial structure with the original version which indicates an adequate validity of the test for Colombian population with chronic disease. © Servicio de Publicaciones - Universidad de Murcia

High-level detection of gene amplification and chromosome aneuploidy in extracted nuclei from paraffin-embedded tissue of human cancer using FISH: a new approach for retrospective studies

A novel application of fluorescence in situ hybridization (FISH) to isolated nuclei is described. The method detects gene amplification and chromosome aneuploidy in extracted nuclei from paraffin-embedded tissue of human cancer with greater sensitivity and specificity than existing FISH methods. In this study, the method is applied to signal detection of the HER-2/neu (c-erbB-2) gene, whose amplification is one of the most common genetic alterations associated with human breast cancer. Nuclei were extracted and isolated from formalin fixed, paraffin embedded tissue of 43 different carcinomas (breast, ovary, endometrium, gastrointestinal stromal tumor and malignant mesothelioma). FISH was performed both on sections and extracted nuclei of each tissue using chromosome enumeration probes (CEP) for the centromeric regions of chromosomes 8 and 17, and a locus specific identifier (LSI) for the HER-2/neu oncogene. Differences between ploidy calculated in sections and extracted nuclei were seen in 3 breast carcinomas and 1 gastrointestinal stromal tumor (GIST). Furthermore, 1 breast cancer, previously considered to be borderline for HER-2/neu gene amplification turned out to be clearly amplified. Nuclei extraction and isolation bypass all the problems related to signal interpretation in tissue sections, and the adoption of this new technique, which improves the signal quality in several neoplastic samples, is suggested

Coupled monoubiquitylation of the co-E3 ligase DCNL1 by Ariadne RBR E3 ubiquitin ligases promotes cullin-RING ligase complex remodeling

Cullin-RING E3 ubiquitin ligases (CRLs) are large and diverse multisubunit protein complexes that contribute to about one-fifth of ubiquitin-dependent protein turnover in cells. CRLs are activated by the attachment of the ubiquitin-like protein neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) to the cullin subunits. This cullin neddylation is essential for a plethora of CRL-regulated cellular processes and is vital for life. In mammals, neddylation is promoted by the five co-E3 ligases, defective in cullin neddylation 1 domain-containing 1-5 (DCNL1-5); however, their functional regulation within the CRL complex remains elusive. We found here that the ubiquitin-associated (UBA) domain-containing DCNL1 is monoubiquitylated when bound to CRLs and that this monoubiquitylation depends on the CRL-associated Ariadne RBR ligases TRIAD1 (ARIH2) and HHARI (ARIH1) and strictly requires the DCNL1's UBA domain. Reconstitution of DCNL1 monoubiquitylation in vitro revealed that autoubiquitylated TRIAD1 mediates binding to the UBA domain and subsequently promotes a single ubiquitin attachment to DCNL1 in a mechanism previously dubbed coupled monoubiquitylation. Moreover, we provide evidence that DCNL1 monoubiquitylation is required for efficient CRL activity, most likely by remodeling CRLs and their substrate receptors. Collectively, this work identifies DCNL1 as a critical target of Ariadne RBR ligases and coupled monoubiquitylation of DCNL1 as an integrated mechanism that affects CRL activity and client-substrate ubiquitylation at multiple levels

Building capacity to provide innovative interventions for early psychosis in mental health professionals

Abstract Despite international guidelines, cognitive behavioural therapy for early psychosis (CBTep) is still under-used in daily clinical practice, mainly due to the lack of specific skills among mental health professionals. The aim of the study was to evaluate the feasibility and efficacy of a CBTep training course and to investigate the impact of trainees' variables on the level of skills acquisition. An intensive and graded CBTep training programme consisting of 112 hours of plenary lectures, 30 hours of group supervision and 3 months of practical training was offered to mental health professionals of 65 Italian community Mental Health Centers (CMHCs). CBT expert psychologists were used as the comparison group. Participants underwent pre-planned exams to test the level of skills acquisition and were requested to complete a satisfaction survey. The vast majority of participants (93%) completed the training with medium–high evaluation scores and reported to be highly satisfied with the course. CMHCs staff members achieved high scores in the examinations and no major differences between them and CBT expert psychologists were found in most of the final exam scores. Our results support the feasibility and the efficacy of the training to build specific CBTep capacity in a large cohort of professionals working in Italian Generalist Mental Health Services. Key learning aims (1) To understand the capacity building of a short training programme in CBT for early psychosis dedicated to community mental health professionals. (2) To consider the optimal characteristics of a CBT training programme for early psychosis. (3) To reflect on the feasibility of a CBT training programme for early psychosis in the context of Italian Community Mental Health Services

Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners

AluY-mediated germline deletion, duplication and somatic stem cell reversion in <i>UBE2T</i> defines a new subtype of Fanconi anemia

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.</p

Mechanism and disease-association of E2 conjugating enzymes:lessons from UBE2T and UBE2L3

Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus. However, recent evidence demonstrates that mutations or impairment of the E2s can lead to severe disease states, including chromosome instability syndromes, cancer predisposition, and immunological disorders. Given their relevance to diseases, E2s may represent an important class of therapeutic targets. In the present study, we review the current understanding of the mechanism of this important family of enzymes, and the role of selected E2s in disease