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 Effects of a High Fat Meal on Blood Flow Regulation during Arm Exercise

A diet high in saturated fats results in endothelial dysfunction and can lead to atherosclerosis, a precursor to cardiovascular disease. Exercise training is a potent stimulus though to mitigate the negative effects of a high saturated fat diet; however, it is unclear how high-saturated fat meal (HSFM) consumption impacts blood flow regulation during a single exercise session. PURPOSE: This study sought to examine the impact of a single HSFM on peripheral vascular function during an acute upper limb exercise bout. METHODS: Ten young healthy individuals completed two sessions of progressive handgrip exercise. Subjects either consumed a HSFM (0.84 g of fat/kg of body weight) 4 hours prior or remained fasted before the exercise bout. Progressive rhythmic handgrip exercise (6kg, 12kg, 18kg) was performed for 3 minutes per stage at rate of 1 Hz. The brachial artery (BA) diameter and blood velocity was obtained using Doppler Ultrasound (GE Logiq e) and BA blood flow was calculated with these values. RESULTS: BA blood flow and flow mediated dilation (normalized for shear rate) during the handgrip exercise significant increased from baseline in all workloads, but no differences were revealed in response to the HSFM consumption. CONCLUSION: Progressive handgrip exercise augmented BA blood flow and flow mediated dilation in both testing days; however, there was no significant differences following the HSFM consumption. This suggests that upper limb blood flow regulation during exercise is unaltered by a high fat meal in young healthy individuals.https://scholarscompass.vcu.edu/gradposters/1060/thumbnail.jp

The effect of partial vascular occlusion on oxidative stress and inflammatory markers in young resistance trained individuals

Low-intensity strength training with partial vascular occlusion (PVO)was reported to result in muscle hypertrophy and strength increases similar to high-intensity training without PVO. Resistance training has been reported to increase markers of oxidative stress and inflammation. A recent study reported that PVO by itself may result in elevated oxidative stress markers. The purpose of this study was to examine the effects of PVO on oxidative stress and inflammatory markers. Twelve resistance trained males (18-35yrs) completed three sets of elbow flexion at either moderate (70% 1RM) or low (30% 1RM) intensity with or without PVO. Two rest (R) conditions done with and without PVO were also included. All exercise conditions were done to failure with the exception of one condition done at 30%1RM and repetition matched to the 30%1RM condition with PVO. The seven conditions were completed at least72 hours apart in a counterbalanced fashion over 3-4 weeks. Blood was obtained before and immediately after each condition. Protein carbonyls (PC), glutathione ratio (GSSG/TGSH), xanthine oxidase (XO), oxygen radical absorbance capacity (ORAC), and interleukin-6 (IL-6) were analyzed in the plasma. The addition of PVO impacted the number of repetitions done and time to completion in both the low and moderate intensity conditions. The analysis of PC levels revealed interaction effects which post hoc analysis revealed a time effect for exercise. Glutathione ratio measures revealed a PVO main effect independent of intensity level or time. ORAC analysis revealed significant interaction effects which were intensity x PVO, intensity x time, and PVO x time interactions. XO activity analysis noted an intensity x time interaction resulting from decreases in XO activity over time in both the moderate and low intensity conditions that were not observed in the rest condition. Analysis of IL-6 levels revealed an intensity x time interaction with a significant increase over time for the moderate intensity condition when compared to the rest condition. A PVO x time interaction was also noted and subsequent post-hoc analysis revealed a significant increase over time for the conditions with PVO. This resulted in a greater IL-6 increase over time in conditions with PVO compared to without PVO. The effect of completing each set to failure as opposed to repetitions matched resulted in no differences between low intensity groups without PVO. In summary, this study shows that partial vascular occlusion can increase oxidative stress and inflammation independent of exercise and that combined with low or moderate intensity exercise there was not a significant change in the variables determined using the elbow flexor muscle group

Demonstration of a beam loaded nanocoulomb-class laser wakefield accelerator.

Laser-plasma wakefield accelerators have seen tremendous progress, now capable of producing quasi-monoenergetic electron beams in the GeV energy range with few-femtoseconds bunch duration. Scaling these accelerators to the nanocoulomb range would yield hundreds of kiloamperes peak current and stimulate the next generation of radiation sources covering high-field THz, high-brightness X-ray and γ-ray sources, compact free-electron lasers and laboratory-size beam-driven plasma accelerators. However, accelerators generating such currents operate in the beam loading regime where the accelerating field is strongly modified by the self-fields of the injected bunch, potentially deteriorating key beam parameters. Here we demonstrate that, if appropriately controlled, the beam loading effect can be employed to improve the accelerator's performance. Self-truncated ionization injection enables loading of unprecedented charges of ∼0.5 nC within a mono-energetic peak. As the energy balance is reached, we show that the accelerator operates at the theoretically predicted optimal loading condition and the final energy spread is minimized.Higher beam quality and stability are desired in laser-plasma accelerators for their applications in compact light sources. Here the authors demonstrate in laser plasma wakefield electron acceleration that the beam loading effect can be employed to improve beam quality by controlling the beam charge

Asynchronous Training of Word Embeddings for Large Text Corpora

Word embeddings are a powerful approach for analyzing language and have been widely popular in numerous tasks in information retrieval and text mining. Training embeddings over huge corpora is computationally expensive because the input is typically sequentially processed and parameters are synchronously updated. Distributed architectures for asynchronous training that have been proposed either focus on scaling vocabulary sizes and dimensionality or suffer from expensive synchronization latencies. In this paper, we propose a scalable approach to train word embeddings by partitioning the input space instead in order to scale to massive text corpora while not sacrificing the performance of the embeddings. Our training procedure does not involve any parameter synchronization except a final sub-model merge phase that typically executes in a few minutes. Our distributed training scales seamlessly to large corpus sizes and we get comparable and sometimes even up to 45% performance improvement in a variety of NLP benchmarks using models trained by our distributed procedure which requires $1/10$ of the time taken by the baseline approach. Finally we also show that we are robust to missing words in sub-models and are able to effectively reconstruct word representations.Comment: This paper contains 9 pages and has been accepted in the WSDM201

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

Germline mutations in the tumor suppressor gene PTEN cause PTEN Hamartoma Tumor Syndrome (PHTS). Pediatric patients with PHTS frequently develop lipomas. Treatment attempts with the mTORC1 inhibitor rapamycin were unable to reverse lipoma growth. Recently, lipomas associated with PIK3CA-related overgrowth syndrome were successfully treated with the novel PI3K inhibitor alpelisib. Here, we tested whether alpelisib has growth-restrictive effects and induces cell death in lipoma cells. We used PTEN-haploinsufficient lipoma cells from three patients and treated them with alpelisib alone or in combination with rapamycin. We tested the effect of alpelisib on viability, proliferation, cell death, induction of senescence, adipocyte differentiation, and signaling at 1–100 M alpelisib. Alpelisib alone or in combination with rapamycin reduced proliferation in a concentrationand time-dependent manner. No cell death but an induction of senescence was detected after alpelisib incubation for 72 h. Alpelisib treatment led to a reduced phosphorylation of AKT, mTOR, and ribosomal protein S6. Rapamycin treatment alone led to increased AKT phosphorylation. This effect could be reversed by combining rapamycin with alpelisib. Alpelisib reduced the size of lipoma spheroids by attenuating adipocyte differentiation. Since alpelisib was well tolerated in first clinical trials, this drug alone or in combination with rapamycin is a potential new treatment option for PHTS-related adipose tissue overgrowth

The Novel Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Alpelisib Effectively Inhibits Growth of PTEN-Haploinsufficient Lipoma Cells

Germline mutations in the tumor suppressor gene PTEN cause PTEN Hamartoma Tumor Syndrome (PHTS). Pediatric patients with PHTS frequently develop lipomas. Treatment attempts with the mTORC1 inhibitor rapamycin were unable to reverse lipoma growth. Recently, lipomas associated with PIK3CA-related overgrowth syndrome were successfully treated with the novel PI3K inhibitor alpelisib. Here, we tested whether alpelisib has growth-restrictive effects and induces cell death in lipoma cells. We used PTEN-haploinsufficient lipoma cells from three patients and treated them with alpelisib alone or in combination with rapamycin. We tested the effect of alpelisib on viability, proliferation, cell death, induction of senescence, adipocyte differentiation, and signaling at 1-100 \ub5M alpelisib. Alpelisib alone or in combination with rapamycin reduced proliferation in a concentration- and time-dependent manner. No cell death but an induction of senescence was detected after alpelisib incubation for 72 h. Alpelisib treatment led to a reduced phosphorylation of AKT, mTOR, and ribosomal protein S6. Rapamycin treatment alone led to increased AKT phosphorylation. This effect could be reversed by combining rapamycin with alpelisib. Alpelisib reduced the size of lipoma spheroids by attenuating adipocyte differentiation. Since alpelisib was well tolerated in first clinical trials, this drug alone or in combination with rapamycin is a potential new treatment option for PHTS-related adipose tissue overgrowth

Integrated ground-based and remotely sensed data to support global studies of environmental change

Data centers routinely archive and distribute large databases of high quality and with rigorous documentation but, to meet the needs of global studies effectively and efficiently, data centers must go beyond these traditional roles. Global studies of environmental change require integrated databases of multiple data types that are accurately coordinated in terms of spatial, temporal and thematic properties. Such datasets must be designed and developed jointly by scientific researchers, computer specialists, and policy analysts. The presentation focuses on our approach for organizing data from ground-based research programs so that the data can be linked with remotely sensed data and other map data into integrated databases with spatial, temporal, and thematic characteristics relevant to global studies. The development of an integrated database for Net Primary Productivity is described to illustrate the process