RESUMEN
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.
Asunto(s)
Lesión Encefálica Crónica/etiología , Lesión Encefálica Crónica/patología , Encéfalo/patología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/patología , Anciano , Apolipoproteínas E/genética , Traumatismos en Atletas/complicaciones , Traumatismos en Atletas/genética , Traumatismos en Atletas/metabolismo , Traumatismos en Atletas/patología , Encéfalo/metabolismo , Lesión Encefálica Crónica/genética , Lesión Encefálica Crónica/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Estudios Retrospectivos , Bancos de Tejidos , Proteínas tau/genética , Proteínas tau/metabolismoRESUMEN
Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS subjects (8,224 AS and 1,437 APA), including changes in ALS-associated genes (for example, ATXN2 and FUS), and in subjects with sporadic ALS (sALS; 2,229 AS and 716 APA). Furthermore, heterogeneous nuclear ribonucleoprotein H (hnRNPH) and other RNA-binding proteins are predicted to be potential regulators of cassette exon AS events in both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Cerebelo/metabolismo , Lóbulo Frontal/metabolismo , Regulación de la Expresión Génica/genética , Proteínas/genética , ARN/metabolismo , Transcriptoma/genética , Adulto , Anciano , Empalme Alternativo , Proteína C9orf72 , Estudios de Asociación Genética , Ribonucleoproteína Heterogénea-Nuclear Grupo F-H/metabolismo , Humanos , Persona de Mediana Edad , Poliadenilación/genética , Análisis de Secuencia de ARNRESUMEN
Social media, also known as Web 2.0, includes a set of web-based technologies in which users actively share and create content through open collaboration. The current students in dental school are Millennial learners who are comfortable using social media, such as Facebook and Twitter, for both socialization and learning. This article defines and explores the range of Web 2.0 technologies available for use in dental education, addresses their underlying pedagogy, and discusses potential problems and barriers to their implementation.