Translational Medical Research Commons^™

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations and Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …

Advocating For Our Patients Using Clinical Research, Brandon Baker

Clinical Research in Practice: The Journal of Team Hippocrates

This reflection is about experiences trying to relate medical research evidence to actual patient care. This piece talks about shared decision-making about screening mammography.

Splenic Biopsies Are Underutilized Due To Overestimation Of Bleeding Risks, Nicholas Destefano

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Civardi G, Vallisa D, Berte R, et al. Ultrasound-guided fine needle biopsy of the spleen: high clinical efficacy and low risk in a multicenter Italian study. Am J Hematol. 2001 Jun;67(2):93-9. doi:10.1002/ajh.1085

Dental Health Practices In Us College Students: The American College Health Association-National College Health Assessment Findings, Lori Dewald Edd, Atc, Mches, F-Aahe

Journal of Health Disparities Research and Practice

Objective: The purpose of this study is to investigate the dental health seeking practices of US college students. Participants: The total number of college students who participated in the ACHA-NCHA survey from 2000-2013 was 1,201,531. Methods: The data requested were the demographic questions and the dental health question from both the ACHA-NCHA I and II. The data were analyzed using SPSS version 20. Results: The percentage of students who reported having a dental exam and cleaning in the last year averaged 76.6% in this study period of time. However, dental health care declined annually following their freshman year. More females …

Targeting Iκb Kinase Β In Adipocyte Lineage Cells For Treatment Of Obesity And Metabolic Dysfunctions, Robert N. Helsley, Yipeng Sui, Se-Hyung Park, Zun Liu, Richard G. Lee, Beibei Zhu, Philip A. Kern, Changcheng Zhou

Clinical and Translational Science Faculty Publications

IκB kinase β (IKKβ), a central coordinator of inflammation through activation of nuclear factor-κB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKβ and found that IKKβ ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKβ ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKβ signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKβ in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of …

The Fertility Problem Inventory And Infertility-Related Stress: A Case Study, Staci L. Born, Jennifer J. Preston

The Qualitative Report

More than seven million people of childbearing age in the United States experience infertility. Oftentimes, for women, the experience of infertility is stressful. The Fertility Problem Inventory (FPI) has been used to quantitatively measure women’s experience of infertility-related stress. However, the construct of infertility-related stress is poorly described in existing literature. The purpose of this case study was to understand how women experience the FPI as a measure of infertility-related stress. To address this issue, women who were undergoing infertility treatment completed the FPI and participated in unstructured interviews. Archival documents were also retrieved to corroborate findings and satisfy saturation. …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Abnormal Uterine Bleeding Guidelines And Clinical Practice Are Based On Poor Quality Evidence, Mirek Mychajlowycz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: A randomized controlled trial. Obstet Gynecol. 2006 Oct;108(4):924-929. doi:10.1097/01.AOG.0000238343.62063.22

Induced Hypothermia Post Cardiac Resuscitation Works In Hospitalized Patients But Not During Transport To Hospital, A Logical Inconsistency Of Evidence, Joshua Frederick

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kim F, Nichol G, Maynard C, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest. JAMA 2013;311(1):45-52. doi:10.1001/jama.2013.282173

Defining Quality In Medical Practice, Nicholas E. Boggs

Clinical Research in Practice: The Journal of Team Hippocrates

We need physicians who are willing to participate in creating the standard of care, and to hold insurance companies accountable for real evidence-based quality markers. Only then will patients receive adequate care and we as educators in medicine be able to adequately teach the next generation of physicians.

From The Editors, John Dawdy, J. Timothy Caldwell

Clinical Research in Practice: The Journal of Team Hippocrates

Editorial introduction to the third issue of Clinical Research in Practice: The Journal of Team Hippocrates.

The Role Of Ng2 Proteoglycan In Glioma., Sridevi Yadavilli, Eugene I Hwang, Roger J. Packer, Javad Nazarian

Neurology Faculty Publications

Neuron glia antigen-2 ((NG2), also known as chondroitin sulphate proteoglycan 4, or melanoma-associated chondroitin sulfate proteoglycan) is a type-1 membrane protein expressed by many central nervous system (CNS) cells during development and differentiation and plays a critical role in proliferation and angiogenesis. 'NG2' often references either the protein itself or the highly proliferative and undifferentiated glial cells expressing high levels of NG2 protein. NG2 glia represent the fourth major type of neuroglia in the mammalian nervous system and are classified as oligodendrocyte progenitor cells by virtue of their committed oligodendrocyte generation in developing and adult brain. Here, we discuss NG2 …

Role Of Proteolipid Protein In Hsv-1 Entry In Oligodendrocytic Cells, Raquel Bello-Morales, Antonio Jesús Crespillo, Beatriz Praena, Enrique Tabarés, Yolanda Revilla, Elena García, Alberto Fraile-Ramos, Wia Baron, Claude Krummenacher, José Antonio López-Guerrero

College of Science & Mathematics Departmental Research

Herpes simplex virus type 1 (HSV-1) has the ability to enter many different hosts and cell types by several strategies. This highly prevalent alphaherpesvirus can enter target cells using different receptors and different pathways: fusion at a neutral pH, low-pH-dependent and low-pH-independent endocytosis. Several cell receptors for viral entry have been described, but several observations suggest that more receptors for HSV-1 might exist. In this work, we propose a novel role for the proteolipid protein (PLP) in HSV-1 entry into the human oligodendrocytic cell line HOG. Cells transfected with PLP-EGFP showed an increase in susceptibility to HSV-1. Furthermore, the infection …

Providing Hands-On Training With Bioinformatics Databases: A Collaboration Between Vcu Libraries & Wright Center For Clinical And Translational Research, Karen H. Gau, Julie A. Arendt, Amy Olex, Aaron R. Wolen

VCU Libraries Faculty and Staff Presentations

Background
With the goal of increasing specialized services for researchers, Virginia Commonwealth University (VCU) Libraries sent its basic science librarians to an intensive training on bioinformatics databases, “A Librarian’s Guide to NCBI.” VCU’s Wright Center for Clinical and Translational Research (Wright CCTR) was expanding the educational component of its bioinformatics support around the same time. This year, the librarians partnered with the Wright CCTR to offer an introductory bioinformatics database workshop introducing researchers to genetic/genomic databases.

Methods
For one week in June, sessions were conducted introducing up to 30 faculty and staff to The Cancer Genome Atlas and NCBI’s Gene, …

Privatization Of Biomedical Research: A Short Term Answer With Long Term Consequences, Frederick Azalekor

Nebraska College Preparatory Academy: Senior Capstone Projects

Biomedical research owned by the government is now available to be owned by private institutions. This results in stagnant innovations because researchers have trouble with all the restrictions that are placed by private institutions. Privatization of biomedical research has short term positive effects but its negative effects are overarching and disastrous. One way to combat this, is for licenses to be deployed slowly with future consequences in mind.

• Privatization has short term benefits but long term disadvantages are disastrous. • To reduce damaging effect, privatization must be deployed slowly and carefully. • Patents or proprietary ownership must be given …

Ready, Set, Network! Research Speed Networking For Clinicians, Scientists And Engineers, Pamela M. Dillon, Karen H. Gau

VCU Libraries Faculty and Staff Presentations

Objectives: A 2013 Institute of Medicine report urged researchers to “engage in additional substantive and productive collaborations” to address important clinical/translational science questions. To encourage team science among our researchers, Tompkins-McCaw Library for the Health Sciences and Center for Clinical and Translational Research hosted a speed networking event, specifically targeting engineers, clinicians, and basic scientists; an analysis of the event is below.

Methods: Invitations were distributed to clinicians, engineers, and basic scientists. To maximize interactions without increasing time spent at the event, researchers were divided into three groups. The event was planned such that each group would meet everyone from …

The Effects Of Resistance Training Frequency On Muscle Hypertrophy And Strength In Healthy Trained Individuals: Literature Review, Alexander C. Boivin

Honors Undergraduate Theses

The purpose of this study is to determine the effects of increased resistance training frequency on strength and hypertrophy in trained individuals. Six Studies were deemed eligible based on the inclusion exclusion criteria. The inclusion criteria for this review were healthy trained individuals. “Trained” refers to over one year of resistance training experience. Exclusion Criteria were study’s that examined either untrained or obese individuals as participants. The evidence indicates a dose-response trend in frequency. Resistance training each muscle group twice a week may be superior compared to once per week. Further more, resistance training each muscle group three times a …

Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris

Theses and Dissertations

Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …

Characterizing The Oncogenic Properties Of C-Terminal Binding Protein, Evan T. Sumner

Theses and Dissertations

The paralogous C-terminal binding proteins (CtBP) 1 and 2 are evolutionarily conserved transcriptional coregulators that target and disrupt the expression of several genes essential for multiple cellular processes critical to regulating tumor formation. CtBP’s ability to govern the transcription of genes necessary for apoptosis, tumor suppression, invasion/migration and EMT gives rise to its oncogenic activities. Both isoforms of CtBP are found to be overexpressed in cancers including colorectal, pancreatic, ovarian, and breast, with higher levels correlating to lower overall median survival. Although multiple lines of evidence suggest CtBP plays a role in tumorigenesis, it has never been formally characterized as …

Neural Crest Cell-Autonomous Roles Of Fibronectin In Cardiovascular Development., Xia Wang, Sophie Astrof

Department of Medicine Faculty Papers

The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

The Role Of Fat Grafting And Adipose-Derived Stem Cells In Breast Reconstruction, Krishna S. Vyas

Theses and Dissertations--Clinical and Translational Science

Fat grafting is a common surgical procedure that involves the transfer of fat from one area of the body to another in order to improve contour deformities, such as in breast reconstruction. Advantages of the technique include using autologous tissue rather than a foreign body and the added benefit of having liposuction to remove fat from an undesirable location. Although adipose tissue could be the ideal soft tissue filler, fat grafting is plagued by tremendous variability in long-term retention, with volume survival rates of 20-80%, resulting in suboptimal outcomes and repetitive procedures.

The mechanisms contributing to long-term fat graft survival …

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …

Effect Of Fluid Temperature And Volume On Thermoregulation In The Heat, Michelle M. Johannsen

Graduate Student Theses, Dissertations, & Professional Papers

The link between thermoregulation, hydration status, and exercise performance in hot humid environments is controversial. The purpose of this study was to evaluate the effects of volume and temperature of ingested fluid on hydration status, thermoregulation and exercise performance. Recreationally active males (N=11, 24.7±5.9 years; VO₂max=58.2±6.0 mL/kg/min) completed two 3-hour intermittent exercise trials in the heat (31^o WBGT=35.5°C with 50% humidity). Participants consumed either 1 mL/kg body weight (BW) of room temperature water (35.5°C; ROOM) or 0.5 mL/kg of an ice slurry mixture (~0°C; COLD) every ten minutes throughout the trials in a randomized crossover design. Subjects …

Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations Of Conps’ Pharmacokinetics, Efficacy, And Mechanisms Of Action, Philip R. Mcdonagh Iii

Theses and Dissertations

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH₂), dextran T10-polyethylene …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Attitudes Toward Breast Cancer Genetic Testing In Five Special Population Groups, Amelie G. Ramirez, Patricia Chalela, Kipling J. Gallion, Edgar Muñoz, Alan E. Holden, Linda Burhansstipanov, Selina A. Smith, Evaon Wong-Kim, Stephen W. Wyatt, Lucina Suarez

Journal of Health Disparities Research and Practice

Purpose: This study examined interest in and attitudes toward genetic testing in 5 different population groups.

Methods: The survey included African American, Asian American, Latina, Native American, and Appalachian women with varying familial histories of breast cancer. A total of 49 women were interviewed in person. Descriptive and nonparametric statistical techniques were used to assess ethnic group differences.

Results: Overall, interest in testing was high. All groups endorsed more benefits than risks. There were group differences regarding endorsement of specific benefits and risks: testing to “follow doctor recommendations” (p=0.017), “concern for effects on family” (p=0.044), “distrust of modern medicine” (p=0.036), …

Racial Disparities In The Association Between Stress And Preterm Birth, Saba W. Masho, Sarah Kye Price, Patricia Anne Kinser, Nancy Jallo

Journal of Health Disparities Research and Practice

Background: High levels of maternal stress have been linked to preterm births. However, findings from previous studies are inconsistent due to the varied use of stress measures. This study examined the effect of maternal stress on preterm birth, using both psychosocial and physiological measures.

Methods: This study was conducted among 231 pregnant women enrolled during their first prenatal care visit. Presence of stress was assessed at enrollment using the Perceived Stress Scale (PSS) and Stressful Life Events Inventory (SLEI). Samples of maternal salivary cortisol were obtained during the first trimester and birth outcomes were ascertained at delivery. Multiple …

Community Based Participatory Research: The Application And Lessons Learned From A Study With Lgb College Students, Caitlin M. Stover

Journal of Health Disparities Research and Practice

Lesbian, gay, and bisexual (LGB) individuals are members of a vulnerable group where health disparities have been identified. To gain a better understanding of the LGB college student healthcare experience and its contribution to the healthcare disparities found in LGB population, a community based participatory research (CBPR) approach was used to fill the gap. This paper will outline the CBPR process with an emphasis on how the principle investigator applied the tenets of CBPR when working with a local LGB college community. Several lessons learned from the research process are also shared in this paper.