Digital Commons Network^™

Generalised Anxiety Disorder – A Twin Study Of Genetic Architecture, Genome-Wide Association And Differential Gene Expression, Matthew N. Davies, Serena Verdi, Andrea Burri, Maciej Trzaskowski, Minyoung Lee, John M. Hettema, Rick Jansen, Dorret I. Boomsma, Tim D. Spector

Psychiatry Publications

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was …

Integrating Basic Research With Prevention/Intervention To Reduce Risky Substance Use Among College Students, Danielle Dick, Linda C. Hancock

Psychiatry Publications

Too often basic research on etiological processes that contribute to substance use outcomes is disconnected from efforts to develop prevention and intervention programming. Substance use on college campuses is an area of concern where translational efforts that bring together basic scientists and prevention/intervention practitioners have potential for high impact. We describe an effort at a large, public, urban university in the United States to bring together researchers across the campus with expertise in college behavioral health with university administration and health/wellness practitioners to address college student substance use and mental health. The project “Spit for Science” examines how genetic and …

A Brief Analysis Of Suicide Methods And Trends In Virginia From 2003 To 2012, Sameer Hassamal, Lori Keyser-Marcus, Ericka Crouse Breden, Kathrin Hobron, Atit Bhattachan, Ananda Pandurangi

Psychiatry Publications

Background. The objective is to analyze and compare Virginia suicide data from 2003 to 2012 to US suicide data. Methods. Suicide trends by method, age, gender, and race were obtained from Virginia’s Office of the Chief Medical Examiner’s annual reports. Results. Similar to US suicide rates, suicide rates in Virginia increased between 2003 and 2012 from 10.9/100,000 people to 12.9/100,000 people. The most common methods were firearm, asphyxia, and intentional drug overdose, respectively. The increase in asphyxia (𝑟 = 0.77, 𝑃 ≤ 0.01) and decrease in CO poisoning (𝑟 = −0.89, 𝑃 ≤ 0.01) were significant. Unlike national trends, intentional …

Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You

Biochemistry and Molecular Biology Publications

mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …

The Phosphorylated Prodrug Fty720 Is A Histone Deacetylase Inhibitor That Reactivates Erα Expression And Enhances Hormonal Therapy For Breast Cancer, Nitai C. Hait, Dorit Avni, Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Hiroaki Aoki, Catherine I. Dumur, Z Zelenko, E J. Gallagher, D Leroith, Sheldon Milstien, Kazuaki Takabe, Sarah Spiegel

Biochemistry and Molecular Biology Publications

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of …

Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O’Hanlon, Zendra E. Zehner

Biochemistry and Molecular Biology Publications

MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was …

Understanding Host-Switching By Ecological Fitting, Sabrina B. L. Araujo, Mariana Pires Braga, Daniel R. Brooks, Salvatore J. Agosta, Eric P. Hoberg, Francisco W. Von Hartenthal, Walter A. Boeger

Biology Publications

Despite the fact that parasites are highly specialized with respect to their hosts, empirical evidence demonstrates that host switching rather than co-speciation is the dominant factor influencing the diversification of host-parasite associations. Ecological fitting in sloppy fitness space has been proposed as a mechanism allowing ecological specialists to host-switch readily. That proposal is tested herein using an individual-based model of host switching. The model considers a parasite species exposed to multiple host resources. Through time host range expansion can occur readily without the prior evolution of novel genetic capacities. It also produces non-linear variation in the size of the fitness …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin J. C. G. Van Den Oord

Biomarker Research and Personalized Medicine Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …

Screening And Brief Intervention For Alcohol Misuse In Older Adults: Training Outcomes Among Physicians And Other Healthcare Practitioners In Community-Based Settings, Constance L. Coogle, Myra G. Owens

Forensic Science Publications

Screening and brief intervention (SBI) is increasingly available to older adults who engage in at-risk drinking. This study examined the extent to which SBI training influenced the willingness of healthcare providers in a community-based hospital and other clinical settings to promote the implementation of SBI. Ninety-three healthcare practitioners (primarily physicians, nurses, and social workers) who attended SBI training were asked about their intentions to apply the information in their professional practice, as well as their enthusiasm about recommending the training to others in their profession. Although there were no differences among the professions in terms of commitment to apply the …

Procalcitonin Identifies Cell Injury, Not Bacterial Infection, In Acute Liver Failure, Jody A. Rule, Linda S. Hynan, Nahid Attar, Corron Sanders, William J. Korzun, William M. Lee, Acute Liver Failure Study Group

Health Administration Publications

Background

Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.

Method

Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls.

Results …

High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia And Renal Failure In Nephrectomized Ldl Receptor Knockout Mice: Role Of Intestine Derived Lipopolysaccharide, Siddhartha S. Ghosh, Samuel Righi, Richard Krieg, Le Kang, Daniel Carl, Jing Wang, H. Davis Massey, Domenic A. Sica, Todd W. B. Gehr, Shobha Ghosh

Anatomy and Neurobiology Publications

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham …

Elucidating The Role Of Injury-Induced Electric Fields (Efs) In Regulating The Astrocytic Response To Injury In The Mammalian Central Nervous System, Matthew L. Baer, Scott C. Henderson, Raymond J. Colello

Anatomy and Neurobiology Publications

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal …

Adiposity And Spinal Cord Injury, Ashraf S. Gorgey, Kathryn M. Wells, Timothy L. Austin

Physical Medicine and Rehabilitation Publications

The drastic changes in body composition following spinal cord injury (SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction …

Ultrasound-Guided Glenohumeral Joint Injection Using The Posterior Approach, Carl P. C. Chen, Henry L. Lew, Chih-Chin Hsu

Physical Medicine and Rehabilitation Publications

Injection treatment to the glenohumeral joint is often needed to treat shoulder problems such as adhesive capsulitis. This can be done through blind palpation technique and fluoroscopic or musculoskeletal ultrasound guidance. In recent years, ultrasound has been proven to increase the accuracy of needle placement into the glenohumeral joint. Ultrasound is radiation free and offers real-time images in performing needle-guided injection procedures.

Glenohumeral joint injection can be done using the anterior rotator interval approach or the posterior approach technique. Both techniques are generally well tolerated by the patients. However, it was shown that the posterior injection technique offers an easier …

Structural Studies Of Aav2 Rep68 Reveal A Partially Structured Linker And Compact Domain Conformation, Faik N. Musayev, Francisco Zarate-Perez, Martino Bardelli, Clayton Bishop, Emil F. Saniev, R. Michael Linden, Els Henckaerts, Carlos R. Escalante

Medicinal Chemistry Publications

Adeno-associated virus (AAV) nonstructural proteins Rep78 and Rep68 carry out all DNA transactions that regulate the AAV life cycle. They share two multifunctional domains: an N-terminal origin binding/nicking domain (OBD) from the HUH superfamily and a SF3 helicase domain. A short linker of ~20 amino acids that is critical for oligomerization and function connects the two domains. Although X-ray structures of the AAV5 OBD and AAV2 helicase domains have been determined, information about the full-length protein and linker conformation is not known. This article presents the solution structure of AAV2 Rep68 using small-angle X-ray scattering (SAXS). We first determined the …

Plasmin Regulation Through Allosteric, Sulfated, Small Molecules, Rami A. Al-Horani, Rajesh Karuturi, Domonique T. White, Umesh R. Desai

Medicinal Chemistry Publications

Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%). Michaelis-Menten kinetic studies revealed …

Prevalence And Factors Predictive Of Intraocular Fungal Infection In Patients With Fungemia At An Academic Urban Tertiary Care Center, Elena Geraymovych, Joseph H. Conduff, Puneet S. Braich, Christopher T. Leffler, Vikram S. Brar

Ophthalmology Publications

Objective: To report the prevalence and to identify factors predictive of intraocular infection in patients with fungemia receiving prophylactic antifungal therapy.
Methods: A retrospective review of patients who received prophylactic antifungal therapy and a dilated fundus examination at an academic urban tertiary care center from 2000 to 2007. Basic demographic information, fungal species grown, antifungal agent(s) used, number of positive blood culture specimens, visual acuity, visual symptoms, and known risks of disseminated candidiasis were noted. Logistic regression analysis was used to determine the factors significantly associated with intraocular fungal infection.
Results: A total of 132 patients with positive fungemia culture …

A Fatal Twist: Volvulus Of The Small Intestine In A 46-Year-Old Woman, Jared Klein, Kathryn Baxstrom, Stephen Donnelly, Patrick Feasel, Paul Koles

Pediatrics Publications

A 46-year-old woman presented to two emergency departments within 12 hours because of acute abdominal pain. Physical exam demonstrated tenderness and epigastric guarding. An ultrasound was interpreted as negative; she was discharged home. Later that evening, she was found dead. Postmortem exam revealed acute hemorrhagic necrosis of a segment of jejunum secondary to volvulus. Clinical clues suggesting presentations of small bowel volvulus are usually nonspecific; the diagnosis is typically confirmed at surgery. Her unremitting abdominal pain, persistent vomiting, and absolute neutrophilia were consistent with an acute process. The etiology of this volvulus was caused by an elastic fibrous band at …

Γ-Secretase Inhibitor Alleviates Acute Airway Inflammation Of Allergic Asthma In Mice By Downregulating Th17 Cell Differentiation, Weixi Zhang, Xueya Zhang, Anqun Sheng, Cuiye Weng, Tingting Zhu, Wei Zhao, Changchong Li

Pediatrics Publications

T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly …

Chemokine Function In Periodontal Disease And Oral Cavity Cancer, Sinem Esra Sahingur, W. Andrew Yeudall

Periodontics Publications

The chemotactic cytokines, or chemokines, comprise a superfamily of polypeptides with a wide range of activities that include recruitment of immune cells to sites of infection and inflammation, as well as stimulation of cell proliferation. As such, they function as antimicrobial molecules and play a central role in host defenses against pathogen challenge. However, their ability to recruit leukocytes and potentiate or prolong the inflammatory response may have profound implications for the progression of oral diseases such as chronic periodontitis, where tissue destruction may be widespread. Moreover, it is increasingly recognized that chronic inflammation is a key component of tumor …

Critical Appraisal Of Dabigatran In The Treatment Of Deep Vein Thrombosis And Pulmonary Embolism, Kelechi C. Ogbonna, Dave L. Dixon

Pharmacotherapy and Outcomes Science Publications

Objective

To compare the safety and efficacy of dabigatran to warfarin for the treatment of deep vein thrombosis and pulmonary embolism.

Background

Venous thromboembolism (VTE) is a disease comprised of two conditions: deep vein thrombosis and pulmonary embolism. VTE is a major cause of morbidity and mortality worldwide with an annual incidence estimated at 1–3 cases per 1,000 individuals. This incidence increases with age from 0.1 per 1,000 in adolescence to eight per 1,000 in those 80 years of age and older. As the proportion of patients 65 years of age and older expands, the number of patients presenting with …

A Simple Method For Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation Of Key Principles From Heparin/Heparan Sulfate-Binding Proteins, Aurijit Sarkar, Umesh R. Desai

Medicinal Chemistry Publications

Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an …

Liver X Receptor-Dependent Inhibition Of Microglial Nitric Oxide Synthase 2, Julie R Secor Mcvoy, Hanadi Ajam Oughli, Unsong Oh

Neurology Publications

Background

The nuclear receptor liver X receptor (LXR) exerts transcriptional control over lipid metabolism and inflammatory response in cells of the myeloid lineage, suggesting that LXR may be a potential target in a number of chronic neuroinflammatory and neurodegenerative diseases where persistent microglial activation has been implicated in the pathogenesis.

Methods

The effect of LXR activation on microglia and central nervous system (CNS) inflammation was studied using a synthetic LXR agonist in cultured microglia, a microglial cell line and experimental allergic encephalomyelitis (EAE), an animal model of CNS inflammation.

Results

LXR activation inhibited nitric oxide synthase 2, inducible (Nos2 …

Virginia Dental Journal (Vol. 92, No. 1, 2015)

Virginia Dental Journal

No abstract provided.

Metagenomic Analysis Of Planktonic Microbial Consortia From A Non-Tidal Urban-Impacted Segment Of James River, Bonnie L. Brown, Rebecca V. Leprell, Rima B. Franklin, Maria C. Rivera, Francine M. Cabral, Hugh L. Eaves, Vicki Gardiakos, Kevin P. Keegan, Timothy L. King

Biology Publications

Knowledge of the diversity and ecological function of the microbial consortia of James River in Virginia, USA, is essential to developing a more complete understanding of the ecology of this model river system. Metagenomic analysis of James River's planktonic microbial community was performed for the first time using an unamplified genomic library and a 16S rDNA amplicon library prepared and sequenced by Ion PGM and MiSeq, respectively. From the 0.46-Gb WGS library (GenBank:SRR1146621; MG-RAST:4532156.3), 4 × 106 reads revealed >3 × 106 genes, 240 families of prokaryotes, and 155 families of eukaryotes. From the 0.68-Gb 16S library (GenBank:SRR2124995; MG-RAST:4631271.3; EMB:2184), …

Mosque Noor, Khizar Khalil

RELS 108 Human Spirituality: Student Perspectives

Student perspectives on worship services from Instructor Jennifer Garvin-Sanchez's Religious Studies 108 Human Spirituality course at Virginia Commonwealth University.

Retention And Mentoring (Ram) Initiative, Grace E. Harris Leadership Institute, Virginia Commonwealth University, Susan Digiovanni, Donna Gibson, Anne Hofler, Florence Johnson, Michael Southam-Gerow, Jenilee Stanley-Shanks

L. Douglas Wilder School of Government and Public Affairs Publications

National and local surveys (e.g., COACHE, 2010; VCU Great Place Initiative, 2013) suggest that a primary reason for workplace dissatisfaction among faculty and staff is lack of adequate mentorship. Evidence also suggests that mentoring programs improve recruitment and retention of underrepresented faculty and staff (e.g., Daley, Wingard, & Reznik, 2006). VCU and VCU Health currently have decentralized and isolated mentoring programs across campuses: a centralized mentoring program accessible to all employees does not exist to address faculty and staff professional development and networking needs. Our project sought to fill this gap. Specifically, we proposed to develop an online database designed …

Promotion, Education, And Marketing Of An Expanded Vcu Bike Share Program, Grace E. Harris Leadership Institute, Virginia Commonwealth University, Kellie Archer, Tom Arodz, Alison Breland, Dawn Crichlow, Tom Klug

L. Douglas Wilder School of Government and Public Affairs Publications

We propose to help promote, market, and provide education about an expanded bike share program at VCU. The goal of the bike share program is three-fold: 1) improve travel between campuses, 2) encourage alternate transportation to reduce traffic and parking difficulties and 3) be a "green" initiative on the VCU campus. The expanded bike share program will include additional bikes and bike stations, managed by an outside company. Recently, VCU’s Office of Parking and Transportation has learned that they will be receiving funds for the program, and they are looking for assistance to promote, market, and provide education about the …

A Website To Help The International Students Experience (Wise), Grace E. Harris Leadership Institute, Virginia Commonwealth University, David Allen, Agnes Chojecka, Tori Keel, Norma Ortiz-Robinson, Susan O'Shea

L. Douglas Wilder School of Government and Public Affairs Publications

Our VCU campus has been steadily expanding its international student population and has become an increasingly global university community. We have identified together with GEO, the need to build tangible resources that can support faculty and staff to more effectively educate our international student population. The creation of online content to be added to GEO’s current webpage seems to best fit the existing need. Our project outlines a blueprint for this online content by means of identifying data and resources that should be included as well as determining cost, sustainability and feasibility plans. Ultimately, the goal is to pave the …

The Artfulness Initiative: Art As A Tool For Mindfulness, Grace E. Harris Leadership Institute, Virginia Commonwealth University, Dvora Courtland, George Deeb, Sarah Golding, Arnold Kemp, Whitney Lovelady, Tito Luna, Molly Ransone, Mary Shelden

L. Douglas Wilder School of Government and Public Affairs Publications

The purpose of the Artfulness Initiative is to help its users bring their minds back into the present through the use of arts-based practices as a way to reduce stress and burnout. In a nutshell, the Artfulness Initiative is website that houses a series of process-oriented art practices meant to help adults focus less on the stress of yesterday and tomorrow and focus more on being in the now. It’s important to note that the art process is more important than the product, and that no artistic aptitude or experience is required. The Artfulness website, which was built by ALTLab …