Temple University

About: Temple University is a education organization based out in Philadelphia, Pennsylvania, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 32154 authors who have published 64375 publications receiving 2219828 citations.

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Abstract: Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

Age differences in affective decision making as indexed by performance on the Iowa Gambling Task.

Abstract: Contemporary perspectives on age differences in risk taking, informed by advances in developmental neuroscience, have emphasized the need to examine the ways in which emotional and cognitive factors interact to influence decision making. In the present study, a diverse sample of 901 individuals between the ages of 10 and 30 were administered a modified version of the Iowa Gambling Task, which is designed to measure affective decision making. Results indicate that approach behaviors (operationalized as the tendency to play increasingly from the advantageous decks over the course of the task) display an inverted U-shape relation to age, peaking in mid- to late adolescence. In contrast, avoidance behaviors (operationalized as the tendency to refrain from playing from the disadvantageous decks) increase linearly with age, with adults avoiding disadvantageous decks at higher rates than both preadolescents and adolescents. The finding that adolescents, compared to adults, are relatively more approach oriented in response to positive feedback and less avoidant in response to negative feedback is consistent with recent studies of brain development, as well as epidemiological data on various types of risky behavior, and may have important practical implications for the prevention of adolescent risk taking.

Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline

Abstract: This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.

Phagocytosis of Microglia in the Central Nervous System Diseases

Abstract: Microglia, the resident macrophages of the central nervous system, rapidly activate in nearly all kinds of neurological diseases. These activated microglia become highly motile, secreting inflammatory cytokines, migrating to the lesion area, and phagocytosing cell debris or damaged neurons. During the past decades, the secretory property and chemotaxis of microglia have been well-studied, while relatively less attention has been paid to microglial phagocytosis. So far there is no obvious concordance with whether it is beneficial or detrimental in tissue repair. This review focuses on phagocytic phenotype of microglia in neurological diseases such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, traumatic brain injury, ischemic and other brain diseases. Microglial morphological characteristics, involved receptors and signaling pathways, distribution variation along with time and space changes, and environmental factors that affecting phagocytic function in each disease are reviewed. Moreover, a comparison of contributions between macrophages from peripheral circulation and the resident microglia to these pathogenic processes will also be discussed.