185 research outputs found

    Genetic Influences on the Neural and Physiological Bases of Acute Threat: A Research Domain Criteria (RDoC) Perspective

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    The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35–50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. © 2015 Wiley Periodicals, Inc

    PTSD co-morbid with HIV: Separate but equal, or two parts of a whole?

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    AbstractApproximately 30 million people currently live with HIV worldwide and the incidence of stress-related disorders, such as post-traumatic stress disorder (PTSD), is elevated among people living with HIV as compared to those living without the virus. PTSD is a severely debilitating, stress-related psychiatric illness associated with trauma exposure. Patients with PTSD experience intrusive and fearful memories as well as flashbacks and nightmares of the traumatic event(s) for much of their lives, may avoid other people, and may be constantly on guard for new negative experiences. This review will delineate the information available to date regarding the comorbidity of PTSD and HIV and discuss the biological mechanisms which may contribute to the co-existence, and potential interaction of, these two disorders. Both HIV and PTSD are linked to altered neurobiology within areas of the brain involved in the startle response and altered function of the hypothalamic-pituitary-adrenal axis. Collectively, the data highlighted suggest that PTSD and HIV are more likely to actively interact than to simply co-exist within the same individual. Multi-faceted interactions between PTSD and HIV have the potential to alter response to treatment for either independent disorder. Therefore, it is of great importance to advance the understanding of the neurobiological substrates that are altered in comorbid PTSD and HIV such that the most efficacious treatments can be administered to improve both mental and physical health and reduce the spread of HIV

    SDS-PAGE analysis of soluble proteins in reconstituted milk exposed to different heat treatments

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    This paper deals with the investigation of the impact of the heat treatment of reconstituted skim milk conducted at different temperatures, and the adding of demineralized whey on the protein solubility, soluble protein composition and interactions involved between proteins in a chemical complex. Commercial skim milk has been reconstituted and heat treated at 75 degrees C, 85 degrees C and 90 degrees C for 20 minutes. Demineralized whey has been added in concentrations of 0.5%, 1.0 and 2.0%. The soluble protein composition has been determined by the polyacrilamide gel electrophoresis (SDS-PAGE) and by the densitometric analysis. Due to the different changes occurred during treatments at different temperatures, proteins of heat-treated samples containing added demineralized whey have had significantly different solubility. At lower temperatures (75 degrees C and 85 degrees C) the adding of demineralized whey decreased the protein solubility by 5.28%-26.41%, while the addition of demineralized whey performed at 90 degrees C increased the soluble protein content by 5.61%-28.89%. Heat treatments, as well as the addition of demineralized whey, have induced high molecular weight complex formation. beta-Lg, alpha-La and kappa-casein are involved in high molecular weight complexes. The disulfide interactions between denatured molecules of these proteins are mostly responsible for the formation of coaggregates. The level of their interactions and the soluble protein composition are determined by the degree of temperature

    Thyroid Stimulating Hormone Receptor Transcripts in Correlation with Clinical Parameters in Thyroid Carcinoma Patients

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    BACKGROUND: Differentiated thyroid carcinomas (DTC) preserve expression of thyroid stimulating hormone receptor (TSHR). AIM: The aim of our study was to evaluate the expression of mRNA-TSHR in peripheral blood of DTC patients, then to correlate the expression with clinical features: Serum thyroglobulin (sTg) value, initial staging and findings from the whole body scan (WBS), neck ultrasound (US), and total received dose of radioiodine therapy. MATERIALS AND METHODS: Forty patients were divided into three groups according to the treatment response: Patients with incomplete structural response (TCs), incomplete biochemical response (TCb), and excellent responders (TCr). Total RNA was isolated from peripheral blood and used for two-step reverse transcriptase-PCR with appropriate primers. Relative quantification using the ΔCt and 2–ΔΔCt and method was applied. sTg levels were evaluated with chemiluminescent assay. The statistical analysis was performed with Spearman Rank Order Correlation. RESULTS: We found that TCs patients expressed mRNA-TSHR by a 5.37-fold higher level than TCr patients, TCb patients expressed TSHR by an 8.88-fold higher level than TCr patients. A significant negative correlation was detected between sTg and ΔCt (CtTSHR - CtGAPDH) value (R = −0.475; p < 0.05), and between WBS/US findings and ΔCt (R= −0.321; p < 0.05). CONCLUSION: Our data revealed higher expression of mRNA-TSHR in peripheral blood of TCs and TCb compared to TCr patients and analysis revealed a significant correlation between mRNA-TSHR and sTg and US/WBS findings. Further studies with larger number of subjects and absolute quantification are needed for understanding the real meaning of mRNA-TSHR as a biomarker in DTC

    Differences in MRSA prevalence and resistance patterns in a tertiary center before and after joining an international program for surveillance of antimicrobial resistance

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    Methicillin-resistant Staphylococcus aureus (MRSA) emerged as one of the most important causes of hospital-acquired bloodstream infections (BSIs), especially the multidrug resistant clones. The aim of the present study was to compare prevalence and resistance patterns of MRSA bacteremia in the major tertiary-care academic and referral center in Serbia before and after implementing an active antimicrobial resistance (AMR) surveillance. Laboratory-based before-after study was conducted during a two-year period (January 2012 to December 2013) in Clinical Centre of Serbia. Isolation and identification of bacterial strains were done following standard microbiological procedures. During the AMR surveillance, nearly twice more bloodstream samples were collected compared to the year without surveillance (1,528 vs. 855). In total, 43 isolates of MRSA were identified. MRSA was significantly more prevalent during the AMR surveillance compared to the previous year [14 (66.7%) to 29 (76.3%); P = 0.046]. During the AMR surveillance, MRSA more frequently originated from medical departments compared to intensive care unit, surgical department, and internal medicine (P = 0.027) indicating increasing MRSA infections in patients with less severe clinical condition and no apparent risk factors. Higher prevalence of MRSA and its lower susceptibility to erythromycin were revealed by implementation of active AMR surveillance, which may reflect more thoughtful collection of bloodstream samples from patients with suspected BSI

    Reduced Neural Activation During an Inhibition Task is Associated with Impaired Fear Inhibition in a Traumatized Civilian Sample

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    Introduction: Impaired inhibition of fear in the presence of safety cues and a deficiency in the extinction of fear cues are increasingly thought to be important biological markers of Posttraumatic Stress Disorder (PTSD). Other studies have suggested that there may be altered neural activation during behavioral inhibition tasks in subjects with PTSD. The current study aimed to see whether neural activation during inhibition was reduced in a highly traumatized civilian population, and whether atypical activation was associated with impaired fear inhibition. Methods: The participants were 41 traumatized women (20 PTSD+, 21 PTSD-) recruited from Grady Memorial Hospital in Atlanta, GA. We used a Go/NoGo procedure with functional magnetic resonance imaging (fMRI) in a high-resolution 3T scanner. Participants were instructed to press a button whenever an “X” or “O” appeared on the screen, but not if a red square appeared behind the letter. Participants were assessed for trauma history and PTSD diagnosis, and completed a fear-potentiated startle and extinction paradigm. Results: We found stronger activation in the ventromedial prefrontal cortex (vmPFC) in traumatized subjects without PTSD compared to those with PTSD in the NoGo greater than Go contrast condition. Activation in the vmPFC was negatively correlated with fear-potentiated startle responses during safety signal learning (p=.02) and fear extinction (p=.0002). Conclusions: These results contribute to understanding of how the neural circuitry involved in inhibitory processes may be deficient in PTSD. Furthermore, the same circuits involved in behavioral inhibition appear to be involved in fear inhibition processes during differential fear conditioning and extinction
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