Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease

Accumulating evidence suggests that genetic variants in the SORL1 gene are associated with Alzheimer disease (AD), but a strategy to identify which variants are pathogenic is lacking. In a discovery sample of 115 SORL1 variants detected in 1908 Dutch AD cases and controls, we identified the variant characteristics associated with SORL1 variant pathogenicity. Findings were replicated in an independent sample of 103 SORL1 variants detected in 3193 AD cases and controls. In a combined sample of the discovery and replication samples, comprising 181 unique SORL1 variants, we developed a strategy to classify SORL1 variants into five subtypes ranging from pathogenic to benign. We tested this pathogenicity screen in SORL1 variants reported in two independent published studies. SORL1 variant pathogenicity is defined by the Combined Annotation Dependent Depletion (CADD) score and the minor allele frequency (MAF) reported by the Exome Aggregation Consortium (ExAC) database. Variants predicted strongly damaging (CADD score >30), which are extremely rare (ExAC-MAF <1 × 10 '5) increased AD risk by 12-fold (95% CI 4.2-34.3; P=5 × 10 '9). Protein-truncating SORL1 mutations were all unknown to ExAC and occurred exclusively in AD cases. More common SORL1 variants (ExAC-MAF≥1 × 10 '5) were not associated with increased AD risk, even when predicted strongly damaging. Findings were independent of gender and the APOE-I 4 allele. High-risk SORL1 variants were observed in a substantial proportion of the AD cases analyzed (2%). Based on their effect size, we propose to consider high-risk SORL1 variants next to variants in APOE, PSEN1, PSEN2 and APP for personalized risk assessments in clinical practice

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces:An fMRI study of dissociative identity disorder

Objective: The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as "Emotional Parts" (EP), but mentally avoid these as "Apparently Normal Parts" of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently.Methods: Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black- and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures.Results: Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially.Conclusions: DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP underactivated. The findings support TSDP. Major clinical implications are discussed. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license.</p

Identifying context factors explaining physician's low performance in communication assessment: an explorative study in general practice

Contains fulltext : 97982.pdf (postprint version ) (Open Access)ABSTRACT: BACKGROUND: Communication is a key competence for health care professionals. Analysis of registrar and GP communication performance in daily practice, however, suggests a suboptimal application of communication skills. The influence of context factors could reveal why communication performance levels, on average, do not appear adequate. The context of daily practice may require different skills or specific ways of handling these skills, whereas communication skills are mostly treated as generic. So far no empirical analysis of the context has been made. Our aim was to identify context factors that could be related to GP communication. METHODS: A purposive sample of real-life videotaped GP consultations was analyzed (N = 17). As a frame of reference we chose the MAAS-Global, a widely used assessment instrument for medical communication. By inductive reasoning, we analyzed the GP behaviour in the consultation leading to poor item scores on the MAAS-Global. In these cases we looked for the presence of an intervening context factor, and how this might explain the actual GP communication behaviour. RESULTS: We reached saturation after having viewed 17 consultations. We identified 19 context factors that could potentially explain the deviation from generic recommendations on communication skills. These context factors can be categorized into doctor-related, patient-related, and consultation-related factors. CONCLUSIONS: Several context factors seem to influence doctor-patient communication, requiring the GP to apply communication skills differently from recommendations on communication. From this study we conclude that there is a need to explicitly account for context factors in the assessment of GP (and GP registrar) communication performance. The next step is to validate our findings

Person-Related Protective and Vulnerability Factors of Psychopathology Symptoms in Non-Clinical Adolescents

Psychopathology in youths is thought to originate from a dynamic interplay of a variety of protective and vulnerability factors. In this study, a large multi-ethnic sample of non-clinical adolescents (N = 376) completed questionnaires for measuring a wide range of person-related protective and vulnerability factors as well as psychopathology symptoms, in order to explore (a) the relations among various protective and vulnerability factors, and (b) the unique contributions of these protective and vulnerability factors to different types of psychological problems. Results indicated that the overlap among protective and vulnerability factors was quite modest. Further, it was found that factors clustered in theoretically meaningful components reflecting protection, vulnerability, and more specific aspects of coping and social support. Finally, data indicated that each type of psychopathology symptoms was associated with a typical set of protective and vulnerability factors. Although these results should be interpreted with caution because of the cross-sectional nature of the study, they may nevertheless guide future research exploring multifactorial models of psychopathology in youths

Pesquisa em educação médica conduzida por estudantes: um ano de experiência do núcleo acadêmico de pesquisa em educação Médica

A pesquisa em educação médica vem se desenvolvendo muito nos últimos anos. A participação de estudantes nos processos de mudanças curriculares também é crescente e bastante contributiva. Ainda, a iniciação científica está sendo amplamente defendida por seu impacto positivo na formação profissional. Relatamos um ano de experiência do Núcleo Acadêmico de Pesquisa em Educação Médica (Napem), que integra as propostas de participação discente nas discussões de ensino médico através de trabalhos de iniciação científica em educação médica. O Napem foi fundado em 2008 e foi bem aceito na comunidade acadêmica da Faculdade de Medicina de Botucatu/Universidade Estadual Paulista (FMB/Unesp). Seus projetos de pesquisa atuais investigam: avaliação do curso médico, avaliação do estudante, fatores que influenciam a busca por iniciação científica, Ligas Acadêmicas e interdisciplinaridade. Estão envolvidos 17 estudantes e dez professores. Em um ano, o Napem apresentou trabalhos em congressos, publicou artigo em periódico indexado e está certificado como grupo de pesquisa no CNPq. Dentre seus desafios estão a necessidade de contínua renovação dos estudantes e o avanço nas pesquisas, de modo que os projetos não se encerrem em si mesmos, mas constituam um continuum de investigação à medida que novas informações sejam agregadas ao conhecimento

Context factors in general practitioner-patient encounters and their impact on assessing communication skills--an exploratory study

Contains fulltext : 118212.pdf (publisher's version ) (Open Access)BACKGROUND: Assessment of medical communication performance usually focuses on rating generically applicable, well-defined communication skills. However, in daily practice, communication is determined by (specific) context factors, such as acquaintance with the patient, or the presented problem. Merely valuing the presence of generic skills may not do justice to the doctor's proficiency.Our aim was to perform an exploratory study on how assessment of general practitioner (GP) communication performance changes if context factors are explicitly taken into account. METHODS: We used a mixed method design to explore how ratings would change. A random sample of 40 everyday GP consultations was used to see if previously identified context factors could be observed again. The sample was rated twice using a widely used assessment instrument (the MAAS-Global), first in the standard way and secondly after context factors were explicitly taken into account, by using a context-specific rating protocol to assess communication performance in the workplace. In between first and second rating, the presence of context factors was established. Item score differences were calculated using paired sample t-tests. RESULTS: In 38 out of 40 consultations, context factors prompted application of the context-specific rating protocol. Mean overall score on the 7-point MAAS-Global scale increased from 2.98 in standard to 3.66 in the context-specific rating (p<0.00); the effect size for the total mean score was 0.84. In earlier research the minimum standard score for adequate communication was set at 3.17. CONCLUSIONS: Applying the protocol, the mean overall score rose above the level set in an earlier study for the MAAS-Global scores to represent 'adequate GP communication behaviour'. Our findings indicate that incorporating context factors in communication assessment thus makes a meaningful difference and shows that context factors should be considered as 'signal' instead of 'noise' in GP communication assessment. Explicating context factors leads to a more deliberate and transparent rating of GP communication performance

Hear my Voice: Understanding how community health workers in the Peruvian Amazon expanded their roles to mitigate the impact of the COVID-19 pandemic through Community-Based Participatory Action Research

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Introduction: The COVID-19 pandemic led to the collapse of the Peruvian health system, which disrupted healthcare access for indigenous communities in the Amazon. We aimed to understand how the COVID-19 pandemic transformed the responsibilities of community health workers (CHWs) from indigenous communities in the Peruvian Amazon so policymakers can support indigenous health efforts. Methods: Fourteen CHWs from Loreto, Peru participated in a community-based Participatory Action Research (CBPR) project using Photovoice, a technique that encourages vulnerable groups to take photos and develop stories illustrating their lived experiences. Participants were recruited from Mamás del Río, a local university-based program, through purposive sampling. CHWs were trained in Photovoice and asked to photograph how the pandemic affected their lives and work. Participants met four times over five months to share photos and develop action items. Data were organized into key themes using a general inductive method. Final photos and action items were shared with policymakers during galleries in Iquitos and Lima. Results: CHWs took a total of 36 photos with 33 accompanying texts highlighting their roles during the pandemic. Four core themes emerged: (1) the collapse of social infrastructure, (2) the use of medicinal plants versus pharmaceuticals, (3) the community adaptations and struggles, and (4) the importance of CHWs. CHWs expanded their responsibilities or leveraged their leadership across these themes to support COVID-19 patients, vaccination, and mandates without training or resources from the government. CHWs asked policymakers for formal integration into the health system, standardization of CHW training, and better management of community pharmacies. Conclusion: CHWs, who work on a voluntary basis, took on additional roles during the pandemic with little to no training from the government. CHWs demonstrated how their roles could be better supported by the government to ameliorate future health catastrophes in the Peruvian Amazon.This item is part of the College of Medicine - Phoenix Scholarly Projects 2022 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]