Posttraumatic stress disorder among veterans of the Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) wars: Psychological comorbidities, postdeployment social support and unit support

Much attention has been given to treating Operation Iraqi Freedom/Operation Enduring (OIF/OEF) Veterans with posttraumatic stress disorder (PTSD). However, little attention is given to those Veterans who do not meet diagnostic criteria for PTSD but who may still benefit from intervention. Research is needed to investigate the impact of how different racial/ethnic backgrounds, different levels of social support and comorbid mental health disorders impact OIF/OEF Veterans with varying levels of PTSD. The purpose of this dissertation is to examine the association of comorbid Axis I disorders, race/ethnicity, different levels of postdeployment social support and unit support on OIF/OEF Veterans with varying levels of PTSD. Data for this dissertation were from postdeployment screenings of OIF/OEF Veterans from a large Veterans Affairs hospital in southeast Texas. To examine the study hypotheses, we conducted multinomial logistic regressions of the clinician reported data. ^ The first article examined the prevalence of subthreshold and full levels of PTSD and compared Axis I and alcohol use comorbidity rates among 1,362 OIF/OEF Veterans with varying levels of PTSD. Results suggest that OIF/OEF Veterans with subthreshold PTSD experience similar levels of psychological distress as those with full PTSD and highlight the need to provide timely and appropriate mental health services to individuals who may not meet the diagnostic criteria for full PTSD. ^ These results suggest that OIF/OEF Veterans of all race/ethnicities can benefit from strong social support systems. Postdeployment social support was found to be a protective factor against the development of PTSD among White, Black and Hispanic veterans while deployment unit support was a protective factor only among Black Veterans. The second article investigated the association between postdeployment social support and unit support with varying levels of PTSD by race/ethnicity among 1,115 OIF/OEF Veterans. ^ The results of this study can help to formulate treatment and interventions for OIF/OEF Veterans with varying levels of PTSD and social support systems.^

Treatment modalities of female Operation Iraqi Freedom/Operation Enduring Freedom Veterans with posttraumatic stress disorder: A systematic review of the literature

Objective. To review professional literature regarding treatment modalities of post-traumatic stress disorder (PTSD) amongst female Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veterans, to assess the efficacy of these treatment options, and to summarize implications of the findings from this literature. Design. Systematic review of published literature. Data sources. Medline, Pubmed, Psycinfo. Review Methods. Articles selected for the literature review pertain to the treatment options of female OIF or OEF veterans who have a diagnosis of PTSD. In addition, other relevant articles, such as articles that discuss the prevalence of the problem, access to care, and similar treatment modalities for PTSD in other war settings, were selected for background information for the review. Results. The search strategy identified 1,305 potential journal articles, taken from thorough searches in Medline, Pubmed, and Psycinfo. These articles were then imported into Refworks. Following final screening, there were 18 articles included in the systematic review and 28 articles used as background information. The remaining articles were excluded following screening of abstract and/or full text of articles. Treatment modalities presented in these trials include: Exposure Therapy (average of 68% reduction in PTSD symptoms), Imagery Rehearsal Therapy (23% reduction), Body-Oriented Therapy (57% reduction), Electroconvulsive Therapy (35% reduction), Holographic Reprocessing (47% reduction), a self-defense training program (13% reduction), Cognitive Behavioral Therapy (65% reduction) and a variety of pharmacotherapies (antipsychotics at 81% reduction, sympatholytic drug at 100% reduction). Outcomes of the studies included in this systematic review were measured by using personal assessment of whether there was a reduction in symptoms of PTSD, based on the results in each study. Conclusion. Overall, all of the treatment modalities investigated in the systematic review proved to be somewhat effective in relieving the burden of symptoms of PTSD amongst female veterans of OIF/OEF. In addition to pharmacotherapy, which had the highest reduction in PTSD symptoms, both the Exposure Therapy and the Cognitive Behavioral Therapy techniques proved to have the most positive results. As all of the therapies had a positive effect on this population, to some degree, a study needs to be done in the future to compare and contrast the efficacy of each therapy intervention when applied to a standardized population.^

PCR-based assay using occult blood detection cards for detection of diarrheagenic Escherichia coli in specimens from U.S. travelers to Mexico with acute diarrhea.

Large field studies of travelers' diarrhea for multiple destinations are limited by the need to perform stool cultures on site in a timely manner. A method for the collection, transport, and storage of fecal specimens that does not require immediate processing and refrigeration and that is stable for months would be advantageous. This study was designed to determine if enterotoxigenic Escherichia coli (ETEC) and enteroaggregative E. coli (EAEC) DNA could be identified from cards that were processed for the evaluation of fecal occult blood. U.S. students traveling to Mexico during 2005 to 2007 were monitored for the occurrence of diarrheal illness. When ill, students provided a stool specimen for culture and occult blood by the standard methods. Cards then were stored at room temperature prior to DNA extraction. Fecal PCR was performed to identify ETEC and EAEC in DNA extracted from stools and from occult blood cards. Significantly more EAEC cases were identified by PCR that was performed on DNA that was extracted from cards (49%) or from frozen feces (40%) than from culture methods that used HEp-2 adherence assays (13%) (P < 0.001). Similarly, more ETEC cases were detected from card DNA (38%) than from fecal DNA (30%) or by culture that was followed by hybridization (10%) (P < 0.001). The sensitivity and specificity of the card test were 75 and 62%, respectively, compared to those for EAEC by culture and were 50 and 63%, respectively, compared to those for ETEC. DNA extracted from fecal cards that was used for the detection of occult blood is of use in identifying diarrheagenic E. coli.

The burnout syndrome among nurses in an urban acute care hospital

Three hundred fifty-four registered nurses from an urban acute care hospital were examined through self-report questionnaires. Nurses from trauma care, critical care and non-critical care nursing specialties participated in the study. The study focuses were (1) whether sociodemographic characteristics were significantly related to burnout; (2) what was the prevalence estimate of burnout among the population; (3) whether burnout levels differed depending upon nursing specialties and; (4) whether burnout as related to nursing stress, work environment, and work relations was mediated by sociodemographic characteristics.^ Race, age, marital status, education, seniority, rank, nursing education, and birthplace were significantly related to one or more aspects of burnout in the total population. With emotional exhaustion alone the prevalence of burnout was 62%. Using emotional exhaustion and depersonalization combined with reduced sense of personal accomplishment as a measure of burnout, thirty-four percent of the nurses were either in the pre-burnout phase or burned out. The relative importance of sociodemographic characteristics indicated that experience and race were highly significant risk factors.^ Burnout levels differed significantly depending upon nursing specialty. Specifically, levels of emotional exhaustion and depersonalization differed significantly between trauma care and critical care, and trauma care and non-critical care. Personal accomplishment did not differ depending upon nursing specialty. Critical care nurses did not differ significantly from non-critical care nurses on aspect of burnout.^ Race, marital status, education, seniority and rank were significant mediators of emotional exhaustion and depersonalization. The study offers possible explanations for the mediating effect of sociodemographic characteristics on nursing stress, work environment, work relations, emotional exhaustion and depersonalization. ^

Metabolic Regulation of mTOR Activation and Endoplasmic Reticulum Stress in the Heart

When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac function in the ex vivo isolated working rat heart. Doubling the heart’s workload acutely increased rates of glucose uptake beyond rates of glucose oxidation. The concomitant increase in glucose 6-phosphate (G6P) was associated with mTOR activation, endoplasmic reticulum (ER) stress and impaired contractile function. Both rapamycin and metformin restored glycolytic homeostasis, relieved ER stress and rescued contractile function. G6P and ER stress were also downregulated with mechanical unloading of failing human hearts. Taken together, the data support the hypothesis that metabolic remodeling precedes, triggers, and sustains structural remodeling of the heart and implicate a critical role for G6P in load-induced contractile dysfunction, mTOR activation and ER stress. In general terms, the intermediary metabolism of energy providing substrates provides signals for the onset and progression of hypertrophy and heart failure.

OXIDATIVE STRESS BASED STRATEGIES FOR ENHANCING THE EFFICACY OF HISTONE DEACETYLASE INHIBITORS (HDACi)

Histone deacetylase inhibitors (HDACi) are anti-cancer drugs that primarily act upon acetylation of histones, however they also increase levels of intracellular reactive oxygen species (ROS). We hypothesized that agents that cause oxidative stress might enhance the efficacy of HDACi. To test this hypothesis, we treated acute lymphocytic leukemia cells (ALL) with HDACi and adaphostin (ROS generating agent). The combination of two different HDACi (vorinostat or entinostat) with adaphostin synergistically induced apoptosis in ALL. This synergistic effect was blocked when cells were pre-treated with the caspase-9 inhibitor, LEHD. In addition, we showed that loss of the mitochondrial membrane potential is the earliest event observed starting at 12 h. Following this event, we observed increased levels of superoxide at 16 h, and ultimately caspase-3 activation. Pre-treatment with the antioxidant N-acetylcysteine (NAC) blocked ROS generation and reversed the loss of mitochondrial membrane potential for both combinations. Interestingly, DNA fragmentation and caspase-3 activity was only blocked by NAC in cells treated with vorinostat-adaphostin; but not with entinostat-adaphostin. These results suggest that different redox mechanisms are involved in the induction of ROS-mediated apoptosis. To further understand these events, we studied the role of the antioxidants glutathione (GSH) and thioredoxin (Trx). We found that the combination of entinostat-adaphostin induced acetylation of the antioxidant thioredoxin (Trx) and decreased intracellular levels of GSH. However, no effect on Trx activity was observed in either combination. In addition, pre-treatment with GSH ethyl ester, a soluble form of GSH, did not block DNA fragmentation. Together these results suggested that GSH and Trx are not major players in the induction of oxidative stress. Array data examining the expression of genes involved in oxidative stress demonstrated a differential regulation between cells treated with vorinostat-adaphostin and entinostat-adaphostin. Some of the genes differentially expressed between the combinations include aldehyde oxidase 1, glutathione peroxidase-5, -6, peroxiredoxin 6 and myeloperoxidase. Taken together, these experimental results indicate that the synergistic activity of two different HDACi with adaphostin is mediated by distinct redox mechanisms in ALL cells. Understanding the mechanism involved in these combinations will advance scientific knowledge of how the action of HDACi could be augmented in leukemia models. Moreover, this information could be used for the development of effective clinical trials combining HDACi with other anticancer agents.