THE IMPACT OF POSTTRAUMATIC STRESS DISORDER ON PERIPHERAL VASCULAR FUNCTION

The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. Peripheral vascular dysfunction may be a mechanism by which PTSD increases CVD risk via increases in oxidative stress, inflammation, and/or sympathetic nervous system activity. PURPOSE: This study sought to examine peripheral vascular function in those with PTSD compared to age-matched controls. METHODS: Eight individuals with PTSD (5 women, 3 men; age 22 ± 2 years), and sixteen healthy controls (CON; 10 women, 6 men, 23 ± 2 years), participated in the study. Leg vascular function was assessed via passive leg movement (PLM) technique and evaluated with Doppler ultrasonography. PLM-induced increases in leg blood flow were quantified as peak change in blood flow from baseline (ΔPeak LBF) and blood flow area under the curve (LBF AUC). RESULTS: Significant differences in leg vascular function were revealed between groups. The PTSD group reported significantly lower ΔPeak LBF (PTSD: 294.16 ± 54.16; CON: 594.78 ± 73.70 ml∙min-1; p = 0.01) and LBF AUC (PTSD: 57.23 ± 24.37; CON: 169.92 ± 29.84 ml; p = 0.02) when compared to the CON group. CONCLUSION: This study revealed that lower limb vascular function is impaired in individuals with PTSD when compared to healthy counterparts.https://scholarscompass.vcu.edu/gradposters/1043/thumbnail.jp

Vascular Dysfunction and Posttraumatic Stress Disorder: Examining the Role of Oxidative Stress and Sympathetic Activity

Purpose: The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. The goal of the study was to better elucidate the mechanisms behind the increased CVD risk by examining peripheral vascular function, a precursor to CVD. Moreover, this study sought to determine the role of oxidative stress and sympathetic nervous system (SNS) activity in PTSD-induced vascular dysfunction. Methods: Sixteen individuals with PTSD (10 women, 6 men; age 24 ± 4 years), and twenty-four healthy controls (CTRL; 15 women, 9 men, 24 ± 4 years), participated in the study. The PTSD group participated in two visits, consuming either a placebo or antioxidant cocktail (AO - vitamins C and E and alpha lipoic acid) prior to their visits, in a randomized order. Arm vascular function was assessed via the reactive hyperemia- induced flow mediated dilation of the brachial artery (BAFMD) technique and evaluated with Doppler ultrasonography. Brachial artery and arm microvascular function were determined by percent change of diameter from baseline normalized for BA shear rate (BAD/Shear), and blood flow area under the curve (BF AUC), respectively. Heart rate variability (HRV) was used to assess autonomic nervous system activity. Results: BF AUC was significantly lower (p = 0.02) and SNS activity was significantly higher (p = 0.02) in the PTSD group when compared to the CTRL group. BAD/Shear was not different between groups. Following the acute AO supplementation, BF AUC was augmented to which it was no longer significantly different (p = 0.16) when compared to the CTRL group. SNS activity within the PTSD group was significantly reduced (p=.007) following the AO supplementation when compared to the PL condition, and the difference between PTSD and CTRL was no longer significant (p=.41). Conclusion: Young individuals with PTSD demonstrated lower arm microvascular, but not brachial artery, function as well as higher sympathetic activity when compared to healthy controls matched for age, sex, and physical activity level. Furthermore, this microvascular dysfunction and SNS activity was attenuated by an acute AO supplementation to the level of the healthy controls. Taken together, this study revealed that the modulation of oxidative stress, via an acute AO supplementation, improved vascular dysfunction in individuals with PTSD, potentially by reducing the substantial SNS activity associated with this disorder.https://scholarscompass.vcu.edu/gradposters/1084/thumbnail.jp

Effects of Dietary Sodium Intake on Blood Flow Regulation During Exercise in Salt Resistant Individuals

PURPOSE: Dietary sodium intake guidelines is ≤2,300 mg/day, yet is exceeded by 90% of Americans. This study examined the impact of a high sodium diet on blood flow regulation during exercise. METHODS: Six males (25 ± 2 years) consumed dietary sodium intake guidelines for two weeks, with one week salt-capsule supplemented (HS: 6,900 mg/day of sodium) and the other week placebo-capsule supplemented (LS: 2,300 mg/day of sodium). At the end of each week, peripheral hemodynamic measurements [blood flow (BF), shear rate (SR), and flow mediated dilation (FMD)/SR)] of the brachial and superficial femoral artery were taken during handgrip (HG) and plantar flexion (PF) exercise, respectively. Each exercise workload was 3 minutes and progressed by 8 kilograms until exhaustion. RESULTS: There were no differences between LS and HS in blood pressure (82 ± 4 v 80 ± 5 mmHg; p = 0.3) or heart rate (56 ± 6 v 59 ± 10 bpm; p = 0.4). HG and PF exercise increased BF, SR, and FMD/SR across workload (p \u3c 0.03 for all), but no difference between diets (p \u3e 0.05 for all). CONCLUSION: Despite previous reports that HS impairs resting vascular function, this study revealed that peripheral vascular function and blood flow regulation during exercise is not impacted by a HS diet.https://scholarscompass.vcu.edu/gradposters/1082/thumbnail.jp

The Effect of Urban Street Gang Densities on Small Area Homicide Incidence in a Large Metropolitan County, 1994–2002

The presence of street gangs has been hypothesized as influencing overall levels of violence in urban communities through a process of gun–drug diffusion and cross-type homicide. This effect is said to act independently of other known correlates of violence, i.e., neighborhood poverty. To test this hypothesis, we independently assessed the impact of population exposure to local street gang densities on 8-year homicide rates in small areas of Los Angeles County, California. Homicide data from the Los Angeles County Coroners Office were analyzed with original field survey data on street gang locations, while controlling for the established covariates of community homicide rates. Bivariate and multivariate regression analyses explicated strong relationships between homicide rates, gang density, race/ethnicity, and socioeconomic structure. Street gang densities alone had cumulative effects on small area homicide rates. Local gang densities, along with high school dropout rates, high unemployment rates, racial and ethnic concentration, and higher population densities, together explained 90% of the variation in local 8-year homicide rates. Several other commonly considered covariates were insignificant in the model. Urban environments with higher densities of street gangs exhibited higher overall homicide rates, independent of other community covariates of homicide. The unique nature of street gang killings and their greater potential to influence future local rates of violence suggests that more direct public health interventions are needed alongside traditional criminal justice mechanisms to combat urban violence and homicides

Evidence for core exosome independent function of the nuclear exoribonuclease Rrp6p

The RNA exosome processes and degrades RNAs in archaeal and eukaryotic cells. Exosomes from yeast and humans contain two active exoribonuclease components, Rrp6p and Dis3p/Rrp44p. Rrp6p is concentrated in the nucleus and the dependence of its function on the nine-subunit core exosome and Dis3p remains unclear. We found that cells lacking Rrp6p accumulate poly(A)+ rRNA degradation intermediates distinct from those found in cells depleted of Dis3p, or the core exosome component Rrp43p. Depletion of Dis3p in the absence of Rrp6p causes a synergistic increase in the levels of degradation substrates common to the core exosome and Rrp6p, but has no effect on Rrp6p-specific substrates. Rrp6p lacking a portion of its C-terminal domain no longer co-purifies with the core exosome, but continues to carry out RNA 3′-end processing of 5.8S rRNA and snoRNAs, as well as the degradation of certain truncated Rrp6-specific rRNA intermediates. However, disruption of Rrp6p–core exosome interaction results in the inability of the cell to efficiently degrade certain poly(A)+ rRNA processing products that require the combined activities of Dis3p and Rrp6p. These findings indicate that Rrp6p may carry out some of its critical functions without physical association with the core exosome

Custom Integrated Circuits

Contains reports on nine research projects.Analog Devices, Inc.International Business Machines CorporationJoint Services Electronics Program Contract DAAL03-89-C-0001U.S. Air Force - Office of Scientific Research Contract AFOSR 86-0164BDuPont CorporationNational Science Foundation Grant MIP 88-14612U.S. Navy - Office of Naval Research Contract N00014-87-K-0825American Telephone and TelegraphDigital Equipment CorporationNational Science Foundation Grant MIP 88-5876

Custom Integrated Circuits

Contains reports on ten research projects.Analog Devices, Inc.IBM CorporationNational Science Foundation/Defense Advanced Research Projects Agency Grant MIP 88-14612Analog Devices Career Development Assistant ProfessorshipU.S. Navy - Office of Naval Research Contract N0014-87-K-0825AT&TDigital Equipment CorporationNational Science Foundation Grant MIP 88-5876

Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer

Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies

Wess-Zumino Current and the Structure of the Decay tau^- to K^-K^+ pi^- nu_tau

We present the first study of the vector (Wess-Zumino) current in tau^-\to K^-pi^-K^+\nu_\tau decay using data collected with the CLEO III detector at the Cornell Electron Storage Ring. We determine the quantitative contributions to the decay width from the vector and axial vector currents. Within the framework of a model by Kuhn and Mirkes, we identify the quantitative contributions to the total decay rate from the intermediate states \omega\pi, \rho^{(\prime)}\pi and K^{*}K.Comment: 10 pages postscript, als available through http://www.lns.cornell.edu/public/CLNS/2003/, accepted by PR