Every spring the Graduate School Association sponsors a research symposium to present graduate research work to the VCU and local Richmond community. The event is an excellent opportunity for graduate students to present their original research and creative projects in a professional but relaxed environment. This is the only opportunity for many graduate students to showcase their work at VCU. Participation in this event has nearly doubled every year and attracts not only VCU students and faculty, but local media, legislators, and respected members of the Richmond business community.
Youssef Abouhussien and Gennady Miloshevsky
Kapton films are widely utilized in harsh radiation environments where radiation resistant insulating materials are required. For space applications, Kapton polymers are used on satellites as substrates for solar arrays and outer layers of thermal systems. Kapton is also used in nuclear power plants as wire insulation. Kapton materials can be exposed in nuclear reactors to a reactive chemical environment in addition to severe radiation. It is of utmost important to understand how Kapton materials behave under high irradiation conditions and mitigate radiation damage effects. High-energy electrons can deposit ionizing dose and electric charge deeply inside Kapton materials. The charge accumulation grows over time and may exceed the dielectric strength of Kapton resulting in the electrostatic discharge that may cause extensive material damage. The dose deposition and electrostatic charging of Kapton irradiated with electrons has been studied using the Monte Carlo stepping model implemented in the Geant4 software toolkit. The secondary radiation emission (photo-, Auger-, Compton-electrons, and fluorescence photons) generated by primary electrons is taken into account in the redistribution of dose and charge deposition within a Kapton film. The results of this study are the profiles of dose and charge deposited by primary and generated secondary electrons and photons within a thin film of Kapton as a function of its depth. The results also provide insights into distributions of dose and charge in Kapton films under various incidence angles and energies of electrons.
Temporal Behavior of the Individual Soft Microparticles: Understanding the Detection by Particle Impact Electrochemistry
Junaid Ahmed and Julio C. Alvarez
Emerging progress of the Particle Impact Electrochemistry (PIE) technique has opened a novel field of detection and characterization of many analyte particles. 1 PIE comprises detection of changes in current when collisions of individual micro or nanoparticles are linked with an electrochemical event at the surface of an ultramicroelectrode (UME). 2 Being a rapid, low cost, and analyzing of one analyte at a time, PIE is widely used to characterize the shape, size distribution, and catalytic activity of nanoparticles. 2-5 To explore the scope of PIE for the detection of soft microparticles (absence of crystalline structure), ferrocene (Fc) trapped toluene-in-water emulsion droplets was used as a model with ultramicroelectrode. Droplets were analyzed by tracking the oxidation of Fc inside the droplet in the presence of an ionic liquid acting as emulsifier and conductivity enhancer. The droplet diameter was determined electrochemically using Faraday’s law. PIE was able to characterize the polydisperse size distribution of the droplets successfully. A 3D lattice random walk simulation indicated the stochastic nature of the droplet motion. Unlike nanoparticles, the droplets have slow kinetics and the collision dynamics associated with adsorption on the electrode surface. The adsorbing droplet generated similar spike-like electrical signals in real-time experiments that follow the bulk electrolysis model. These findings will facilitate the characterization of polydisperse microparticles including bacteria, which also adsorb and have similar size and density as the droplets in this work. Finally, because electrolysis time spans from hundreds of milliseconds to a second, single events of such duration are detectable with present-day instrumentation in contrast to non-adsorbing nanoparticles that have nanosecond collisions.
Local Lung Targeting of Tumor Associated Macrophages Combined with Cytoreductive Therapy Decrease Tumor Burden in a Secondary Lung Cancer Model
Sulaiman Alhudaithi, Hanming Zhang, Rashed Almuqbil, Wei Du, Fatemah Sunbul, Paula Bos, and Sandro da Rocha
Backgrounds. The efficacy of a locally administered small molecule colony stimulating factor 1 receptor inhibitor (CSF-1Ri), PLX3397, alone or in combination with cytoreductive therapy (paclitaxel) in reducing the tumor burden of an in vivo model of secondary lung cancer was investigated in this work. Local administration of immunotherapy to the lungs may enhance lung biodistribution of such therapies and reduce potential unwanted off-target toxicity. In addition, combination of such therapy with low dose standard of care chemotherapy may offer improved anti-tumor effects.
Methods. Murine breast cancer cells (4T1, known to be highly metastasized to the lungs) were transduced to express the genes luciferase and tdTomato, and cells were injected to female Balb/c mice before being treated with PLX (intratracheally administered), paclitaxel (intravenously given), or the combination therapy. Both ex vivo bioluminescent imaging and lung weights were used to evaluate tumor burden. Western blot was performed using lung tumors to assess the effect of PLX3397 on its molecular target (phosphorylated CSF-1R). Immunofluorescence and Flowcytometry were utilized to examine the impact of treatment on tumorigenic tumor associated macrophages (M2 TAM).
Results. Single-agent treatment partially decreased tumor burden, while combination therapy led to a significant reduction in tumor burden. PLX3397 significantly inhibited the expression of phosphorylated CSF-1R and reduced the number of M2 TAM without affecting the total macrophage population, thereby increasing the anti-tumorigenic (M1)/M2 ratio.
Conclusion. Tumor burden reduction upon local administration of PLX3397 to the lungs correlates with the marked inhibition of the molecular target and the decrease in M2 TAM.
Dendrimer Conjugation Enhances Tumor Penetration and Cell Kill of Doxorubicin in 3D Coculture Lung Cancer Models
Rashed Almuqbil, Rodrigo S. Heyder, Elizabeth R. Bielski, Mikhail Durymanov, Joshua J. Reineke, and Sandro R. P. da Rocha
Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX.
Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of (A549) lung adenocarcinoma cells and (3T3) fibroblasts. Spheroids were characterized for ECM components with immunohistochemistry. Confocal microscopy was used to evaluate the penetration, internalization, and colocalization of DOX and G4SA-GFLG-DOX. MTT assay and Caspase 3/7 to assess 2D and 3D cytotoxicity. Flow cytometry to determine cells uptake.
Results: DOX conjugation to dendrimer resulted in G4SA-GFLG-DOX with ~5.5 DOX, 10±1 nm hydrodynamic diameter, and a -17±3 mV zeta-potential. Spheroids of (A549:3T3) were ECM- rich, developed ECM containing collagen-I, hyaluronan, laminin, and fibronectin. While DOX and G4SA-GFLG-DOX had similar toxicities in 2D model, G4SA-GFLG-DOX demonstrated a 3.1-fold greater penetration into spheroids compared to DOX and correlated to a greater efficacy as measured by caspase 3/7 activity. Also, flow cytometry showed higher uptake of G4SA- GFLG-DOX in cancer cells compared to fibroblasts.
Conclusion: The work demonstrates enhanced penetration of DOX, via dendrimer conjugation, into an ECM- rich 3D lung cancer model. The enhanced penetration of G4SA-GFLG-DOX correlated with greater antitumor efficacy.
Acknowledgements: We acknowledge partial financial support from the Center for Pharmaceutical Engineering and Sciences - School of Pharmacy at VCU. This study was supported by VCU Quest for Distinction and NSF (DRM #1508363). Microscopy was performed at the VCU Microscopy Facility, supported, in part, by funding from NIH-NCI Cancer Center Support Grant P30 CA016059. RA would like to acknowledge King Faisal University (KFU) and Saudi Arabian Cultural Mission (SACM) for a scholarship.
Suad Alshammari, Joshua M. Morriss, Daniel Contaifer, Dayanjan S. Wijesinghe, and Monther Alsultan
Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures.
Methods: R scripts were developed under version 3.5.3 with the capability to undertake statistical analyses (e.g. ANOVA) and post-hoc tests (e.g. Tukey). Additional code plotted resultant information as high resolution violin and box plots that depicted statistical significance. Thereafter, lipidomic and metabolomic data were analysed by this code and compared against commercial software and Metaboanalyst, a primary software used in metabolomic and lipidomic research.
Results: Code generated in house demonstrated the same results as those generated using commercial software (e.g. JMP 14.0 Pro) but were different from results obtained by using the MetaboAnalyst pipeline.
Conclusions: This study demonstrated the prevalent danger of using closed-source software pipelines for the analysis of lipidomic and metabolomic data without validating the analysis outcomes via open-source software. Open source software such as LipidAnalyst, that has also been independently validated using multiple data sets, can then be published with the results to enable transparency of data analysis and improve the replicability of results across different labs.
A Pre-transplant Blood-based Lipid Signature for Prediction of Antibody-mediated Rejection in Kidney Transplant Patients
Monther Al sultan, Daniel Contaifer Jr., Joshua Morriss, Suad Alshammari, Jeffrey Stern, Sindhura Bobba, Pamela Kimball, Anne King, Dhiren Kumar, Marlon Levy, Gaurav Gupta, and Dayanjan Wijesinghe
Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients.
Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to create Linear Discrimination Analysis with regularized correction (RLDA). Changes over time were estimated using sparse partial least square method which is validated by permutation testing. T-test was performed to compare two time points for the same group and groups at matched time points. JMP Pro 13 and MetaboAnalyst were used in the analysis of the Data.
Results. A comparison of lipids classes on the day of transplant revealed PLs relative concentration differences between SC and AMR. Concentration of phosphatidylcholine (PC) was significantly diminished in AMR, while there was a trend for increased concentration of lysophosphatidylcholine (LPC). AMR group also showed significantly lower concentration of phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), plasmanylethanolamine (PE-O), and plasmenylethanolamine (PE-P). Our data demonstrated that there are significant differences in the lipidome between SC and AMR on the day of transplant. The analysis identified 7 distinct lipids that discriminated between AMR and SC (AUC) =0.95 (95%CI=0.84- 0.98), R2=0.63 (95%CI=0.4-0.8). A sPLSDA analysis of the data revealed a statistically significant alteration in the lipid profile at 6 months post-transplant compared to the day of transplant. The analysis revealed a panel of 13 lipids that were found to differentiate the two groups at 6 month post-transplant . Further data analysis confirms the presence of a sustained lipid metabolic difference between SC and AMR over time that distinguish between the patients with favorable and non-favorable transplant outcomes.
Conclusion. This study demonstrates the potential of the pre-transplant lipidome towards determining AMR in kidney transplant patients, raising the possibility of using this information in risk stratification of patients about to undergo transplant.
Addressing Minority Health Disparities in Richmond: Results from a Health Needs Assessment of a Southside Community
Nixon Arauz, MA; Shanteney Jackson, MA; and Robert A. Blanco, MPH
Evidence shows the effectiveness of integrating community health workers (CHWs) into care models serving high-risk patients to reduce emergency department (ED) use, increase primary care use, and address adverse social determinants of health (SDH). The Southwood Resource Center, part of a network of clinics established by Richmond City Health Department, utilizes CHWs to address disparities affecting underserved populations through primary care referrals and additional resource linkages. Local student-volunteers in partnership with CHWs conducted a community needs assessment to identify patient resource gaps, aid in design and implementation of SDH interventions, and examine the relationship between chronic disease management and ED use reductions.
English and Spanish-language surveys were conducted during patient visits to the SRC, in addition to other settings to facilitate representative sampling. A total of 134 responses were received, with Blacks (34%) and Hispanic/Latinos (65%) well represented.
Significant social determinants identified by the needs assessment included housing stability, and transportation and food access. Respondents indicated need for support managing chronic conditions including heart disease, diabetes, mental health and asthma. 1 in 3 respondents (31%) reported using the ED for primary care, and nearly 2 in 3 (66%) reported not having a family doctor. Barriers to health care included cost (35.6%), insurance status (50.4%) and transportation access (29.6%).
CHWs play an important role in identifying community strengths and resource gaps and linking patients to additional resources. Opportunities for service improvements include bilingual care coordination, chronic care management, health insurance navigation, food subsistence resources, and transportation support.
Screening for Cognitive Impairment in Primary Brain Tumor Patients: A Preliminary Investigation with the MMSE and RBANS
Farah Aslanzadeh, M.S.; Sarah Braun, M.S; Julia Brechbiel, M.S.; Kelcie Willis, M.S.; Kyra Parker; Autumn Lanoye, PhD; and Ashlee Loughan, PhD
Introduction: The prevalence of mild cognition impairment (MCI) among older adults (≥65) is estimated to range between 10-20% (Langa & Levine, 2014). Integrated primary care allows opportunities for interdisciplinary consultation, screening, and intervention. The aim of this study is to explore the percentage of older adults reporting cognitive concerns during their first primary care psychology visits. It is hypothesized that these rates will mirror prevalence rates in other older adult community dwelling samples in primary care settings.
Methods: A patient sample of older adults (≥60) was introduced to services following a referral from their primary care physician. Clinicians then identified problems that were discussed in session, including “cognitive concerns.” Descriptive statistics will be used to assess the percentage of older adults with “cognitive concerns” in this sample, compared to other community dwelling samples.
Results: 267 older adults were identified within a larger sample of patients who received primary care psychology services. The percentage of older adults who were referred for “cognitive concerns” was 10.5% (n = 28), with 12.7% (n = 34) reporting “cognitive concerns” during their visit. Interestingly of the 28 older adults referred by their provider for “cognitive concerns,” less than 50% (n = 13) of those patients reported “cognitive concerns” as one of their problems in session.
Discussion: This sample of older adults reported cognitive concerns in primary care psychology sessions at a rate that falls within the range identified in other community dwelling samples. Future research could further improve upon identification and screening of older adults with cognitive concerns by psychologists in primary care settings, as intervention for MCI can improve quality of life and may delay progression of dementia (Campbell et al., 2018; Eshkoor et al., 2015).
Suicidal Ideation and Self-injury Prevalence and Impairment in an Urban Integrated Primary Care Clinic
Kathryn L. Behrhorst; Bruce Rybarczyk, Ph.D.; and Heather A. Jones, Ph.D.
Introduction: Suicide is the second leading cause of death for adolescents (Rosenbaum & Ougrin, 2019). Pediatric primary care staff are often the first line of intervention for youth presenting with suicidal thoughts and NSSI (Taliaferro et al., 2013). The primary aim of the current study was to describe reported suicidal ideation, attempts, and NSSI in youth presenting to an urban integrated primary care setting.
Methods: Within an outpatient pediatric primary care clinic, patients were referred by medical staff and introduced to behavioral health services. Patients were asked about their history of suicidal thoughts/attempts and NSSI (Mage = 12.63; SD = 4.51; 66.3% female, 66.3% Black; 69.6% Medicaid). Patients were also screened using the Pediatric Symptom Checklist-17 (PSC17; Gardner et al., 2007) and Top Problems (Weisz et al., 2001).
Results: Seventeen percent of patients endorsed a history of either suicidal ideation/attempts or NSSI. Chi-square analyses identified a significant association between patient race and suicidal ideation/attempts [χ2(6) = 13.56, p = .035]. The sample’s mean internalizing score on the PSC17 fell within the clinical range (M = 6.13, SD = 2.49). Further results reflecting findings, interventions used, and top problem areas will be presented.
Conclusion: Results highlight a demand for establishing and sustaining effective screening and engagement in mental health treatment for youth suicidality and self-injury in integrated care settings. Future directions will be discussed.
Alex Belt, Seth J. Corey, Steven Grant, Robert M. Tombes, and Sarah C. Rothschild
Background: Acute myeloid leukemia (AML) is the second most common type of leukemia. Standard treatment includes chemotherapy as well as stem cell transplantation, but for aging patients and those with impaired immune function these rigorous therapies are not always possible. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) exhibit far worse prognoses than patients without. Given these circumstances new therapies must be developed.
Methods: Danio rerio (zebrafish) has emerged as a powerful model organism for investigating human blood malignancies due to the conservation of hematopoiesis between humans and zebrafish. We developed a transient transgenic model exhibiting AML characteristics by microinjecting single-cell zebrafish embryos with a tissue specific MLL-ENL expression construct.
Results: We found that the expression of MLL-ENL induced a clustered expansion of MLL+ and pu.1+ myeloid cells on the yolk sac at 48 and 72 hours post fertilization (hpf). To characterize our transient AML model, we treated MLL-ENL expressing embryos with either one of or a combination of two drugs that are currently being used in human AML drug trials, Venetoclax and Flavopiridol. We found that treatment with either drug reduced the myeloid expansion induced by the expression of MLL-ENL, and that co-treatment reduced the observed myeloid expansion even further.
Conclusions: Although further analysis is required, these data suggest that we successfully developed a transient transgenic AML model in zebrafish. Furthermore, these data suggest that Venetoclax and Flavopiridol co-treatment could yield better outcomes for AML patients than treatment with either drug individually.
Evaluating the Effectiveness of Shielding Material, Vehicle Shape and Astronaut Position for Deep Space Travel
Daniel Bond, Braden Goddard, Robert Singleterry, and Sama Bilbao y Leon
Background: As future crewed, deep space missions are being planned, it is important to assess how spacecraft design can be used to minimize radiation exposure. Collectively with shielding material, vehicle shape and astronaut position must be used to protect astronauts from the two primary sources of space radiation: Galactic Cosmic Rays (GCRs) and Solar Particle Events (SPEs).
Methods: The On-Line Tool for the Assessment of Radiation in Space (OLTARIS) version 4.1 analysis package is used to evaluate and analyze this detailed radiation field. Developed by the National Aeronautics and Space Administration's (NASA) Langley Research Center, the tool enables engineering and research related space radiation calculations. Each configuration is evaluated in whole body effective dose equivalent (ED). This research evaluates 70 aerospace materials, 2 vehicle shapes and 3 astronaut positions.
Results and Conclusions: The material analyses show that for metals, aluminum outperforms and therefore is the most feasible metal for deep space travel. But when evaluating all materials, polyethylene outperforms all feasible aerospace materials.
The vehicle shape and astronaut position analyses show that moving a human phantom closer to a wall does significantly decrease the ED. This pattern is not dependent on material nor boundary condition, but the mean shielding thickness a source ray must travel through for the GCR boundary condition. For shielding thicknesses greater than 30 g/cm 2 for polyethylene and 100g/cm 2 for aluminum, the results suggest that having astronauts’ habitats and work areas located further from the center will help protect astronauts longer from deep space radiation.
Elastic Foundations as Heterogeneous Adventitial Boundary Condition for the Assessment of Aortic Wall and Peri-Aortic Stiffness from Dense-MRI Data Using Inverse FEM Approach
Johane H. Bracamonte, John S. Wilson, and Joao S. Soares
Background: The establishment of in vivo, patient-specific, and regionally resolved techniques to quantify aortic properties is key for improving risk assessment in clinical practice and scientific understanding of cardiovascular growth and remodeling. Many in vivo studies quantify vascular stiffness using Pulse Wave Velocity. This method provides an averaged measure of stiffness for the entire aorta, ignoring variations in wall stiffness and boundary conditions. Previous studies using Displacement Encoding with Stimulated Echoes Magnetic Resonance Imaging (DENSE-MRI) suggested that the infrarenal abdominal aorta (IAA) deforms heterogeneously throughout the cardiac cycle.
Method: Herein, we hypothesize that the aortic wall strain heterogeneity is driven in healthy aortas by adventitial tethering to perivascular tissues that can be modeled with elastic foundation boundary conditions (EFBC) using a collection of linear-springs with a circumferential distribution of stiffness. Nine healthy-human IAAs were modeled using patient-specific imaging and displacement fields from SSFP and DENSE MRI, followed by assessment of aortic wall properties and heterogeneous EFBC parameters using inverse Finite Element Method (FEM).
Results: In contrast to traction-free boundary condition, prescription of EFBC reduced the nodal displacement error by 60% and reproduced the DENSE-derived strain distribution. Estimated aortic stiffness was in agreement with previously reported experimental test data. The distribution of normalized EFBC stiffness was consistent among all patients and spatially correlated to standard peri-aortic anatomical features.
Conclusion: Results suggest that EFBCs can be generalized for human adults with normal anatomy. This approach is computationally inexpensive, making it ideal for large-population clinical research and incorporation into computational cardiovascular fluid-structure analyses.
Deon Brown, Fantasy Lozada, Zewelanji Serpell, and Vivian Dzokoto
Background: African American culture has long been known for its emphasis on emotion expression (Boykin, 1986). However, African Americans have learned to restrict emotion publicly due to pervasive stereotypes (Consedine & Magai, 2002). It’s likely that such behavior is learned in the family, in which parents alert children to racial discrimination that is typically associated with context (Dunbar et al., 2017). Thus, African Americans are likely to vary emotion expression according to context. The current study explored emotion expression in the family and public context.
Methods: 188 African American/Black college students from 3 different types of college campuses. The sample was 62.4% female, 35.4% male, and 2.2. genderqueer/gender non- conforming. Data were collected via an online survey with all self-report measures. Contextual differences in emotion expression were explored via latent profile analysis (LPA).
Results: Five profiles emerged: More Positive and Negative Submissive Expression (n = 49; 26%), More Family Expression (n = 8; 5%), Low Family and Campus Expression (n = 24; 13%), More Campus Positive and Negative Dominant Expression (n = 45; 24%), and More Positive and Less Negative Dominant Expression (n = 63; 33%). Racial discrimination significantly predicted profile membership for the More Campus Positive and Negative Dominant Expression profile in particular.
Conclusions: African American youth express emotion differently in the family context compared to campus, particularly in the face of racial discrimination. The patterns of emotion expression revealed here are helpful in terms of evaluating outcomes of African American’s emotion-related behavior as taught in the family.
I am a cultural theorist focused primarily on capitalisms as cognitive, behavioral, and productive conditions. I have self-published two books on this topic, titled ‘Distruments’, and ‘Assemblies & Other Essays’. I am currently working on my third, titled, ‘Everything A Waiting Midnight’.
Interdisciplinary inquiry into political, poetic, and philosophical texts by Ana Tsing, Sylvia Wynter, Yannis Ritsos, Sylvia Wynter, and Christina Sharpe.
A book length series of essays and theses, which bridge the gap between my second and third major texts, ‘Assemblies’ and ‘Everything A Waiting Midnight’.
This work attempts to create a constellation of the works before it, while declaring an additional sphere of nuanced critique into the works on and against capital which came before it: that is, that the culture of capital is a culture of discipline-of-life, entirely, and develops, first and foremost (even before that which is the ‘commodity’) a cinema of discipline, which sets the scene for the reproduction of a world where everything has a price. This price is nothing less than life, itself.
Multilevel variance components and brain volume mediation of life stress on post-traumatic stress disorder symptoms in children via regularization
Daniel Bustamante and Michael C. Neale
Alterations of volume in brain regions of interest (ROIs) are associated with post-traumatic stress disorder (PTSD). Most of the extant neuroimaging research in PTSD has studied adults. The present study extends this research by using data from children (N=11,869, M age =9.92) from the ABCD study, a multisite longitudinal long-term study of brain development and childhood health in the U.S. Traumatic events (TEs) and PTSD symptoms were measured through the K- SADS for DSM-5. Values of brain ROIs were assessed using structural MRI measures. The unidirectional model was able to detect the small differences from site variance in sMRI mediators (subc: VS<.009, SE<.004; cort: VS<.009, SE<.004). Additive genetic factors explained 23.49% of the variance in TEs, 41.73% in subcortical and 19.94% in cortical mediators, and residual 21.01% in PTSD symptoms. Environmental factors explained most of the variance in TEs (C=.61, E=.16) and PTSD symptoms (resC=.19, resE=.21), as well as unique environmental factors in the cortical mediators (cort=.66). TEs highly influenced PTSD symptoms (.92). However, the indirect effect of TEs on PTSD symptoms through the mediation of volume in brain ROIs was small to non-influential at this age (subc=-.0003-.001, cort=-.001- .002). Several estimates of mediation effects were notably higher than most. Regularization via elastic net is implemented to train the mediation model to reduce bias and noise from overfitting, and to select the ROIs with mediation effects that explain the data with increased sparsity.
Holly Byers and Larisa Litovchick, MD, PhD
The ability to halt the cell cycle is critical for cells to maintain tissue and organ size, to suppress tumors and abnormal growth, and exists as a helpful mechanism to pause the cell cycle for DNA repair. DYRK1A is (dual specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) a human gene found on the long (q) arm of chromosome 21, which is known to be involved with nervous system development, cell growth and division, and neuronal differentiation. In glioblastoma cells grown in vitro (T98G cell line), there are three copies of DYRK1A, which have dosage- dependent effects on the cell, including association with cognitive delays in Down Syndrome (Trisomy 21), and relevance to cancer (loss of DYRK1A leads to oncogenic transformation of fallopian tube epithelial cells by Ras and p53). In terms of DYRK1A’s role in the cell cycle, it is known as a putative tumor suppressor, mainly through its critical role in phosphorylating a Serine 28 residue on protein LIN52, leading to the formation of the DREAM complex. DREAM promotes exit from the cell cycle and cell quiescence (arrest in G0 phase). Surprisingly, DYRK1A-KO (knockout) cells actually slowed down cell proliferation, which is an unexpected result when knocking out a tumor suppressor. Through several experiments, involving cell cycle flow cytometry, western blotting for protein cell cycle markers, and EdU staining to determine whether these cells were actively undergoing DNA synthesis, we were able to determine that DYRK1A-KO T98G cells were entering the cell cycle and undergoing DNA synthesis more slowly that control cells.
Guadecitabine, in combination with Cyclophosphamide, promotes anti- cancer immunity in BALB/c mice bearing 4T1 mouse mammary carcinoma
Carmen Camarena, Timothy M. Smith, Rebecca K. Martin PhD, and Harry D. Bear MD
Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of MDSCs and T-regs. Methods: Guadecitabine (Guad), is a second-generation DNA methyltransferase inhibitor (DMNTi) that has been reported to increase antigenicity and deplete myeloid-derived suppressor cells (MDSC’s). Cyclophosphamide (Cyp) is a chemotherapy that has been shown to deplete regulatory T-cells (T-regs). Both MDSD’s and T-regs suppress antitumor immunity. BALB/c mice were challenged with 4T1 tumor cells subcutaneously in the mammary fat pad region. 4T1-bearing mice were administered low-dose Guad and Cyp for ten consecutive days. Tumor growth curves, tumor-infiltrating lymphocytes (TILs) were measured and MDSC’s and T- regs levels were assessed by flow cytometry. Results: Results from this experiment showed significant synergy between Guad and Cyp with both drugs reducing the tumor size over monotherapy. Conclusions: Further analysis of the data along with future experiments will elucidate if this synergy is driven by the depletion of MDSC’s and T-regs alone or the increase in tumor antigenicity inducing increased numbers of TILs.
Alexander Chiu, Lauren Pederson, Jeremy O. Via, Natalie J. Bohmke, Jacob Richardson, Aaron Autler, Hunter Reed, Eric Henderson, R. Lee Franco, and Ryan S. Garten
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.
Maria de Jesus Cisneros-Elias, Gabriela Chavira, and Karen Alvarez
With the education crisis of Latinas/os, it is important to understand ways to increase access to college for the most vulnerable youth (Gándara & Contreras, 2009). To investigate strengths that promote college accessibility in underserved Latina/o families, the current qualitative study assessed the following: (1) Prior to beginning the intervention program and after the intervention program what forms of capital did families possess? (2) How did participating in the program change adolescents’ perception of their parents’ capital? (3) How did adolescents use agency to apply what they learned in college information intervention over time?
Latina/o parent-adolescent dyads (N = 11) participated in a college knowledge program in California. Sample included girls (67%) and 11-16 years of age (M = 14.0, SD = 1.78). Five of 11 families were interviewed 6-months post-effects of the intervention program. Research study used grounded theory inductive analysis approach (Corbin & Strauss, 2015).
Question 1, Latina/o adolescents expressed aspirational, familial, navigational, and social capital before and after the intervention. Question 2, After participating in the intervention, adolescents expressed familial support through a combination of tangible (drop me off at school) and intangible (want me to be a good man) acts. Question 3, focused on the 6-month post-effects of the intervention program. Adolescents expressed agency by actively meeting requirements to apply to college, and understanding the path they need to reach their educational goals.
Discussion will focus on the importance of college information intervention programs in increasing Latino/a youth’s education experiences.
Mauli Dalal and Kweki-Muata Osei-Bryson
Social media platforms facilitate user interaction and impact decision making. Users prefer to use hashtags while sharing posts. Knowing the sentiment towards diabetes, bloodpressure, and obesity is fundamental to understanding the impact of these information on patients and their families. The study seeks to determine the relevance of health-related hashtags on Twitter and analyze sentiments about diabetes, obesity, blood pressure.
Tweets were retrieved using synonyms for “diabetes”, “hypertension” and “obesity”. The extended knowledge discovery in data mining (KDDM) model guided our research with research objectives defined in the ‘research problem understanding’ phase. The ‘information seeking’ from Uses and Gratifications Theory (UGT) determined the success and text mining assessment criteria. Text pre-processing was done using tokenization, stop word removal, and stemming. The research objectives, text mining goals, and success criteria were answered using ‘Uses and Gratifications Theory’ (UGT).
Total 6749 tweets were extracted using RStudio. 36.41% were about blood pressure, 0.25%- diabetes, 24.43% -obesity and 6.99% -combination of two or more terms. Additional topics such as cholesterol, chia seeds, postpartum, diet, exercise were identified. Upcoming conferences like ‘#ipna’, ‘#review’, ‘#APCH2019’, ‘#cardiotwitter’ were identified. Increased user engagement – about managing blood pressure, diabetes, obesity across different age groups, as well as the consequences of increased cardio exercise for obese and diabetic users were encouraging. Tweets about advertisements specific to clothing for oversized individuals-initiated conversation among users about monitoring self-health.
Sentiment analysis can thus increase our understanding about user engagement on such platforms and potentially help improve managing public health strategically.
Ashley Darling, Alex Chiu, Eric Henderson, Aaron Autler, Jennifer Weggen, Kevin Decker, and Ryan Garten
Determining the Impact of Increased Physical Activity on Improving Sleep Quality in Young Adults
Disturbed sleep, defined as any alteration to normal sleep patterns, has been linked to poor cardiovascular health and an increase in cardiovascular disease (CVD) risk. These negative sleep patterns are highly prevalent with 35% to 41% of individuals in the United States reported some form of disturbed sleep. Although high amounts of physical activity (PA) are often associated with high sleep quality, little is known about PA’s effectiveness to improve different aspects of sleep (e.g. duration vs quality) and the mechanisms to which it can improve sleep quality.
Purpose: The study sought to determine the ability of increased PA to improve sleep efficiency in healthy young adults.
Methods: Nineteen young adults (25±4 yrs) were recruited for this study. Subjects wore an accelerometer (Actigraph GT3x-BT) for a total of three weeks to record daily physical activity (step count; low, moderate, and vigorous physical activity) and sleep variables (efficiency, wake after sleep onset, number of nightly awakenings, time per awakening, and total sleep time). Subjects maintained normal physical activity levels for the first week (BL), then increased their step count by an average of 5,000 steps/day across the next two weeks (W1 and W2). Heart rate variability (HRV) and venous blood draws were collected weekly to assess sympathetic activity and inflammation, respectively.
Results: The physical activity intervention resulted in significant increases (p < 0.001) in step-count for both W1 (13163 ± 3184) and W2 (12168 ± 3619) when compared to BL (8648 ± 2615 steps/day). No significant differences from BL were observed when examining sleep efficiency (BL: 83.8 ± 6.4; W1: 85.5 ± 4.0; W2: 84.2 ± 6.1 %), sympathetic-vagal balance, and inflammatory marker concentrations in W1 and W2. A significant correlation was revealed when assessing the change in sleep efficiency from BL to W1 (r = 0.81, p < 0.001) and BL to W2 (r = 0.52, p = 0.02) when compared to initial sleep efficiency values.
Conclusion: This study revealed that although young healthy individuals appear to lack improvements in sleep efficiency with an increase in physical activity, those who reported the lowest sleep quality had the greatest improvements in sleep efficiency following an increase in physical activity. Therefore, the findings of the study suggest that although increasing physical activity can improve sleep quality, a potential “ceiling effect” may occur, as when sleep quality is adequate, augmenting physical activity no longer has a substantial effect.
Effects of Dietary Sodium Intake on Blood Flow Regulation During Exercise in Salt Resistant Individuals
Kevin P. Decker, Morgan T. Kimmel, Hunter L. Reed, Alex H. Chiu, Austin C. Hogwood, Jennifer B. Weggen, Ashley M. Darling, and Ryan S. Garten
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 < 0.03 for all), but no difference between diets (p > 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.
THE ASSOCIATIONS BETWEEN SEXUAL VICTIMIZATION AND HEALTH OUTCOMES AMONG LGBQA COLLEGE STUDENTS: EXAMINING THE MODERATING ROLE OF SOCIAL SUPPORT
Eryn DeLaney; Chelsea Derlan Williams; Della V. Mosley; Sage E. Hawn; and Danielle M. Dick, PhD
Sexual victimization is a prevailing public health concern that differentially impacts sexual minority populations (i.e., people who identify as lesbian, gay, bisexual, asexual, or queer) compared with their heterosexual and cisgender counterparts (McCauley et al., 2018). Studies have shown that sexual violence is associated with depressive symptoms, post-traumatic stress disorder symptoms, and alcohol use (Aosved et al., 2011; Bedard-Gilligan et al, 2011; Carey et al., 2018) among heterosexual college students. However, we know less about the potential effects of sexual victimization on health outcomes among sexual minority college students. Understanding these relations are especially important because sexual minority college students often experience unique challenges and are at increased risk of sexual victimization in comparison to their counterparts (Cantor et al., 2015; Edwards et al., 2015). Moreover, few studies to date have examined the moderating role of social support in buffering the links between sexual victimization and health outcomes. Guided by the minority stress framework (Meyer, 2003), the current study examined the extent to which sexual victimization influences health outcomes (i.e., depressive symptoms, post-traumatic stress disorder symptoms, and alcohol use disorder) among sexual minority college students. Furthermore, we examined whether social support moderated the association between sexual victimization and each health outcome. The current study included 234 students who identified as being part of the Queer community (e.g., Gay, Lesbian, Asexual, and Queer) from a larger university-wide study (i.e., Spit for Science; Dick et al., 2014). The participants in the present study were 18-22 years old (M = 18.46, SD = .412) and majority female (i.e., 74%). Fifty-six percent of the participants self- identified as White, 16% as Black or African American, 13% as Asian, and 15% as American Indian, Latinx, Pacific Islander, or Multiracial. Students provided online self-reports of their sexual victimization experiences (Blake et al., 1990), social support (Hays et al., 1995), depressive symptoms (Derogatis et al., 1973), post-traumatic stress disorder symptoms (Weathers et al., 2013) and alcohol use (DSM-V). We used a series of regression models in Mplus v 7.2 (Muthén & Muthén, 1998–2014) to test our research questions, with multiple imputation to handle missing data. Findings indicated that sexual victimization was positively related to depressive symptoms (b = .21, p = .00), post- traumatic stress disorder symptoms (b = .43, p = .00), and alcohol use disorder (b = .45, p = .00). Furthermore, social support significantly moderated the association between sexual victimization and depressive symptoms, however, in a direction contrary to hypotheses. Specifically, greater sexual victimization was associated with greater depressive symptoms among sexual minority college students with higher levels of social support (b = .29, p = .00), and the association was not significant for sexual minority college students with lower levels of social support (b = .13, p = .26; Figure 1). Discussion will center on the detrimental effects of sexual victimization on health outcomes among sexual minority college students, as well as providing potential explanations and future directions for the nuanced ways social support functions in the lives of sexual minority college students.
Katherine W. Dempster; Julia Scheidemantel; Jessica Greenlee; Marcia A. Winter, Ph.D; and Robin S. Everhart, Ph.D
Introduction: Expressed emotion (EE), the affective attitudes and behaviors of one toward another, can affect caregivers’ behaviors toward their child. Research examining associations between EE and child/family outcomes is mixed; these associations may be affected by other influences such as the presence of a chronic disease or parent mental health. In this study of families living in an urban area, we examined associations between EE and child outcomes (anxiety/depressive symptoms) and family functioning, with parent anxiety as a covariate. We evaluated child asthma status as a moderator in these associations as the presence of a chronic illness may strengthen the association between EE and child/family outcomes.
Methods: 96 children (mean±SD age=8.83±2.03 years, 48.9% female, 92.6% African American; 47 with asthma) and their parents (81.3% annual household income<$25,000) completed an observational study including interviews and questionnaires. Measures included the Multidimensional Anxiety Scale for Children (MASC), Children’s Depressive Symptoms Inventory (CDI), Self-Report Family Inventory (SFI), Generalized Anxiety Disorder scale (GAD-7), and Five-Minute Speech Sample (FMSS) coded for EE. To examine study aims, regression analyses were conducted using PROCESS macro version 3.1. Asthma status (yes/no) was examined as a moderator.
Results: EE was associated with child anxiety symptoms, child depressive symptoms, and family functioning, controlling for parent anxiety symptoms (F(1,70) =6.74, p=.011; F(1,69) =7.803, p=.007; F(1,68) =8.637, p=.004). Asthma status did not moderate any of the associations.
Conclusions: Results suggested that high levels of caregiver EE were associated with child mental health symptoms and family functioning, but asthma status did not moderate associations. It is possible that regardless of additional family demands related to asthma, EE is associated with child mental health and family functioning. Further examination into other systemic stressors that may moderate these associations is warranted, as well as the impact that minimizing parent anxiety might have on overall EE.
Emily K. Donovan, Joseph M. Dzierzewski, Constance H. Fung, Karen R. Josephson, Cathy A. Alessi, and Jennifer L. Martin
Background: Older adults often face sleep disturbance or cognitive decline that goes beyond the scope of normal aging. The present study examined the relationship between self-reported sleep quality and self-reported daytime attention in a community-dwelling sample of older men at the between-persons and within-persons levels of association.
Methods: Thirty-eight participants (M age =75.36 years, SD age =7.51 years, range=66-90 years) completed a twice-daily sleep diary for one week. Sleep quality and attention were assessed using a single-item 0-10 rating scales from the morning diary (“How was the quality of your sleep last night?”) and from the evening diary (“How was your attention today?”). A two-level multilevel model was parameterized with days nested within individuals to examine whether nightly sleep quality predicts an individual’s daily attention rating.
Results: A multilevel model predicting self-reported attention revealed (1) older individuals who reported better sleep quality reported having better daily attention [Beta=0.64, t(248.15)=10.12, p<0.001] and (2) following a day of above-average sleep quality, older individuals experienced above-average attention [Beta=0.16, t(259.79)=2.75, p=.006].
Conclusion: Not only was overall sleep quality associated with self-reported attention, but a good night's sleep was associated with better self-reported next-day attention. Results point to the potential importance of fluctuations in sleep quality for daytime functioning. Interventions aimed at improving nightly sleep consistency may be worth exploring as methods to improve daytime cognitive functioning in older adults.
Support: This work was supported by the Sleep Research Society Foundation/Jazz Pharmaceuticals (001JP13, PI: Dzierzewski) and by the National Institute on Aging of the National Institutes of Health under Award Number K23AG049955 (PI: Dzierzewski), and National Heart Lung and Blood Institute at the National Institutes of Health under award number K24HL143055 (PI: Martin). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.