The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases.Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects.Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD

A \u201cde novo\u201d mutation of the LDL-receptor gene as the cause of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene and transmitted as a codominant trait. However, there are some forms of hypercholesterolemia which have a recessive type of transmission. We have identified a subject with the clinical phenotype of heterozygous FH whose parents had normal plasma lipid values, suggesting a recessive type of transmission. The analysis of the LDL-receptor gene revealed that the patient was heterozygous for a G > C transversion in exon 4, which results in a serine for cysteine substitution at position 88 (C88S) of the receptor protein. Since this novel mutation was not found in the proband\u2019s parents and non-paternity was excluded, we concluded that the patient was a carrier of a \u2018\u2018de novo\u2019\u2019 mutation. Haplotype analysis of LDL-receptor locus indicated that this \u2018\u2018de novo\u2019\u2019 mutation occurred in the paternal germ line. The C88S mutation is the likely cause of LDL-receptor defect as it was present in the proband\u2019s hypercholesterolemic son and was not found in 200 chromosomes of control subjects

Selection For Vigilance Assignments: A Review And Proposed New Direction

Vigilance or sustained attention is a critical aspect of operational tasks including air-traffic control, airport security, industrial quality control and inspection, and medical screening and monitoring. Consequently, the selection of personnel for assignments involving vigilance is a key ergonomic concern. As reviewed herein, traditional approaches to personnel selection for tasks requiring vigilance have concentrated on unidimensional measures involving sensory acuity, aptitude, sex, age and personality factors. These approaches have been ineffective. In this article, we suggest an alternative approach in which the selection issue is considered in terms of a theory-driven analysis of different types of vigilance tasks and multidimensional predictors. As an example of that approach, we made use of a resource model of vigilance and measures of cerebral blood flow velocity and subjective state obtained from a short battery of high-workload tasks to successfully predict individual performance on subsequent high-workload sensory and cognitive vigilance tasks. © 2011 Taylor & Francis

Functional Fidelity, Context-Matching, And Individual Differences In Performance

Conventional personality questionnaires are often only weak predictors of operational performance. A major problem is that personality effects are moderated by contextual factors which may be mismatched across laboratory and real-world studies. Context mismatch threatens the \u27functional fidelity\u27 of laboratory performance tasks; the extent to which the individual behaves as they would in the operational environment. Three research strategies for enhancing the functional fidelity of laboratory studies of individual differences are proposed. First, contexts relevant to specific personality traits may be developed in the laboratory. For example, socially threatening environments may be necessary to find meaningful effects of neuroticism. Second, traits linked to a specific performance context may be employed. The validity of traits for driver stress vulnerability supports this approach. Third, psychophysiological responses to simulations of the cognitive demands of the work environment may be used. Our recent work shows that stress and hemodynamic responses to short high-workload tasks predict longer-duration sustained performance. Copyright 2010 by Human Factors and Ergonomics Society, Inc. All rights reserved

The Functional Fidelity Of Individual Differences Research: The Case For Context-Matching

Applying basic research on individual differences in performance requires a kind of \u27functional fidelity\u27. That is, the laboratory environment must elicit individual differences in cognition and emotion similar to those seen in the operational setting. Studies of conventional personality traits and performance often lack this functional fidelity. Four research directions for enhancing functional fidelity are proposed. First, a greater focus on simulated operational tasks that require cognitive skills is requisite. Second, contexts relevant to specific personality traits, such as social demands, may be simulated in the laboratory. Third, traits linked to a specific performance context, such as vehicle driving, may be developed and validated. Fourth, psychophysiological responses to tasks that reproduce operational cognitive demands may be used as predictors, as exemplified in recent studies of vigilance. Enhancements to functional fidelity will assist human factors practitioners in accommodating the role of individual differences in operator selection, diagnostic monitoring and augmented cognition. © 2011 Taylor & Francis

Task Engagement, Cerebral Blood Flow Velocity, And Diagnostic Monitoring For Sustained Attention

Loss of vigilance may lead to impaired performance in various applied settings including military operations, transportation, and industrial inspection. Individuals differ considerably in sustained attention, but individual differences in vigilance have proven to be hard to predict. The dependence of vigilance on workload factors is consistent with a resource model of sustained attention. Thus, measures of attentional resource availability may predict the operator\u27s subsequent vigilance performance. In this study, we investigated whether a diagnostic battery of measures of response to a cognitive challenge would predict subsequent sustained attention. Measures that may relate to the mobilization of resources in response to task demands include subjective task engagement and coping, and a novel psychophysiological index, cerebral bloodflow velocity (CBFV). A two-phase design was used. First, participants were exposed to a challenging battery of short tasks that elevated CBFV. Second, participants performed a 36-min vigilance task. Two subgroups of participants performed either a sensory vigilance (N = 187) or a cognitive vigilance (N = 107) task. Measures of task engagement, coping, and CBFV response to the short task battery were compared as predictors of subsequent vigilance. Both subjective and CBFV indices of energization predicted sensory and cognitive vigilance, consistent with resource theory. Structural equation modeling was used to develop a latent factor model of influences on sustained attention. It is concluded that measures of resources, conceptualized as multiple energization processes, are potentially useful for diagnostic monitoring in applied settings. Use of a diagnostic task battery in military and transportation settings is discussed, along with some potential limitations on validity of the diagnostic test. © 2010 American Psychological Association

Health care reform and integrated care: A golden opportunity for preventive psychiatry

The Affordable Care Act (ACA) includes provisions to shift the U.S. health care system to address achieving wellness rather than just treating illness. In this Open Forum, the Prevention Committee of the Group for the Advancement of Psychiatry describes opportunities created by the ACA for improving prevention of mental illnesses and promotion of mental health. These include improved coverage of preventive services, models to integrate primary and behavioral health care, and establishment of the National Prevention, Health Promotion, and Public Health Council, which has developed a National Prevention Strategy. The authors describe the important role that psychiatrists can play in advancing prevention of mental illnesses, in particular by working to incorporate prevention strategies in integrated care initiatives and by collaborating with primary care providers to screen for risk factors and promote mental and emotional well-being

Genetic polymorphisms affecting the phenotypic expression in familial hypercholesterolemia

reserved12Impact Factor 3.796The clinical expression of heterozygous familial hypercholesterolemia (FH) is highly variable even in patients carrying the same LDL receptor (LDL-R) gene mutation. This variability might be due to environmental factors as well as to modifying genes affecting lipoprotein metabolism. We investigated Apo E (2, 3, 4), MTP (-493G/T), Apo B (-516C/T), Apo A-V (-1131T/C), HL (-514C/T and -250G/A), FABP-2 (A54T), LPL (D9N, N291S, S447X) and ABCA1 (R219K) polymorphisms in 221 unrelated FH index cases and 349 FH relatives with defined LDL-R gene mutations. We found a significant and independent effect of the following polymorphisms on: (i) plasma LDL-C (Apo E, MTP and Apo B); (ii) plasma HDL-C (HL, FABP-2 and LPL S447X); (iii) plasma triglycerides (Apo E and Apo A-V). In subjects with coronary artery disease (CAD+), the prevalence of FABP-2 54TT genotype was higher (16.5% versus 5.2%) and that of ABCA1 219RK and KK genotypes lower (33.0% versus 51.5%) than in subjects with no CAD. Independent predictors of increased risk of CAD were male sex, age, arterial hypertension, LDL-C level and FABP-2 54TT genotype, and of decreased risk the 219RK and KK genotypes of ABCA1. These findings show that several common genetic variants influence the lipid phenotype and the CAD risk in FH heterozygotes.mixedBERTOLINI S; L. PISCIOTTA; DI SCALA L; LANGHEIM S; BELLOCCHIO A; MASTURZO P; CANTAFORA A; MARTINI S; AVERNA M; PES G.M; STEFANUTTI C; CALANDRA SBertolini, Stefano; Pisciotta, Livia; DI SCALA, L; Langheim, S; Bellocchio, A; Masturzo, Paola; Cantafora, A; Martini, S; Averna, M; PES G., M; Stefanutti, C; Calandra, S