University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment: A Meta-analysis of Randomized Controlled Trials

Abstract: ContextThe US Food and Drug Administration (FDA) has issued warnings that use of antidepressant medications poses a small but significantly increased risk of suicidal ideation/suicide attempt for children and adolescents.ObjectiveTo assess the efficacy and risk of reported suicidal ideation/suicide attempt of antidepressants for treatment of pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders.Data Sources and Study SelectionPubMed (1988 to July 2006), relevant US and British regulatory agency reports, published abstracts of important scientific meetings (1998-2006), clinical trial registries, and information from authors. Studies were published and unpublished randomized, placebo-controlled, parallel-group trials of second-generation antidepressants (selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger than 19 years with MDD, OCD, or non-OCD anxiety disorders.Data ExtractionInformation was extracted on study characteristics, efficacy outcomes, and spontaneously reported suicidal ideation/suicide attempt.Data SynthesisTwenty-seven trials of pediatric MDD (n = 15), OCD (n = 6), and non-OCD anxiety disorders (n = 6) were selected, and risk differences for response and for suicidal ideation/suicide attempt estimated by random-effects methods. Pooled risk differences in rates of primary study-defined measures of responder status significantly favored antidepressants for MDD (11.0%; [95% confidence interval {CI}, 7.1% to 14.9%]), OCD (19.8% [95% CI, 13.0% to 26.6%), and non-OCD anxiety disorders (37.1% [22.5% to 51.7%]), corresponding to a number needed to treat (NNT) of 10 (95% CI, 7 to 15), 6 (4 to 8), and 3 (2 to 5), respectively. While there was increased risk difference of suicidal ideation/suicide attempt across all trials and indications for drug vs placebo (0.7%; 95% CI, 0.1% to 1.3%) (number needed to harm, 143 [95% CI, 77 to 1000]), the pooled risk differences within each indication were not statistically significant: 0.9% (95% CI, −0.1% to 1.9%) for MDD, 0.5% (−1.2% to 2.2%) for OCD, and 0.7% (−0.4% to 1.8%) for non-OCD anxiety disorders. There were no completed suicides. Age-stratified analyses showed that for children younger than 12 years with MDD, only fluoxetine showed benefit over placebo. In MDD trials, efficacy was moderated by age, duration of depression, and number of sites in the treatment trial.ConclusionsRelative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD. Benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across indications, although comparison of benefit to risk varies as a function of indication, age, chronicity, and study conditions.

PAMPs and DAMPs: Signal 0s that Spur Autophagy and Immunity

Abstract: Pathogen-associated molecular pattern molecules (PAMPs) are derived from microorganisms and recognized by pattern recognition receptor (PRR)-bearing cells of the innate immune system as well as many epithelial cells. In contrast, damage-associated molecular pattern molecules (DAMPs) are cell-derived and initiate and perpetuate immunity in response to trauma, ischemia, and tissue damage, either in the absence or presence of pathogenic infection. Most PAMPs and DAMPs serve as so-called 'Signal 0s' that bind specific receptors [Toll-like receptors, NOD-like receptors, RIG-I-like receptors, AIM2-like receptors, and the receptor for advanced glycation end products (RAGE)] to promote autophagy. Autophagy, a conserved lysosomal degradation pathway, is a cell survival mechanism invoked in response to environmental and cellular stress. Autophagy is inferred to have been present in the last common eukaryotic ancestor and only to have been lost by some obligatory intracellular parasites. As such, autophagy represents a unifying biology, subserving survival and the earliest host defense strategies, predating apoptosis, within eukaryotes. Here, we review recent advances in our understanding of autophagic molecular mechanisms and functions in emergent immunity.

Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells.

Abstract: In sexual transmission of simian immunodeficiency virus, and early and later stages of human immunodeficiency virus-type 1 (HIV-1) infection, both viruses were found to replicate predominantly in CD4(+) T cells at the portal of entry and in lymphoid tissues. Infection was propagated not only in activated and proliferating T cells but also, surprisingly, in resting T cells. The infected proliferating cells correspond to the short-lived population that produces the bulk of HIV-1. Most of the HIV-1-infected resting T cells persisted after antiretroviral therapy. Latently and chronically infected cells that may be derived from this population pose challenges to eradicating infection and developing an effective vaccine.

Stress-induced eating.

Abstract: Stress is widely thought to lead to overeating. Studies of stress-induced eating have tested two models. One has tested whether stress increases eating in all exposed organisms and has been tested primarily with animals and physical stressors. The other has tested individual differences in vulnerability to stress-induced eating and has tested only human subjects and psychological stressors. The most consistent set of findings shows that "restrained" eating predicts vulnerability among women; we conclude that for the stressors studied to date, the individual-difference model has received stronger support. Because the question motivating much of this research is whether stress-induced eating causes obesity, future research should assess the effect of stress on weight-change more directly.

Gesture Paves the Way for Language Development

Abstract: In development, children often use gesture to communicate before they use words. The question is whether these gestures merely precede language development or are fundamentally tied to it. We examined 10 children making the transition from single words to two-word combinations and found that gesture had a tight relation to the children's lexical and syntactic development. First, a great many of the lexical items that each child produced initially in gesture later moved to that child's verbal lexicon. Second, children who were first to produce gesture-plus-word combinations conveying two elements in a proposition (point at bird and say “nap”) were also first to produce two-word combinations (“bird nap”). Changes in gesture thus not only predate but also predict changes in language, suggesting that early gesture may be paving the way for future developments in language.