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Commonwealth Times 2011-12-01

Commonwealth Times, 1969-

No abstract provided.

Characterization Of The Effect Of Serum And Chelating Agents On Staphylococcus Aureus Biofilm Formation; Chelating Agents Augment Biofilm Formation Through Clumping Factor B, Nabil Mathew Abraham

Theses and Dissertations

Staphylococcus aureus is the causative agent of a diverse array of acute and chronic infections, and some these infections, including infective endocarditis, joint infections, and medical device-associated bloodstream infections, depend upon its capacity to form tenacious biofilms on surfaces. Inserted medical devices such as intravenous catheters, pacemakers, and artificial heart valves save lives, but unfortunately, they can also serve as a substrate on which S. aureus can form a biofilm, attributing S. aureus as a leading cause of medical device-related infections. The major aim of this work was take compounds to which S. aureus would be exposed during infection and …

Childhood Maltreatment, Coping, And Coping Self-Efficacy Among Offenders, David Guion

Theses and Dissertations

This study explored the relationship between childhood interpersonal trauma and coping self-efficacy, coping styles, and emotion regulation difficulties among male and female offenders in detention and diversion centers (N = 183). The coping-relapse model of recidivism posits that offenders’ coping ability plays a pivotal role in successful reentry (Zamble & Quinsey, 1997). Past research reveals that childhood maltreatment is associated with avoidant coping and emotion regulation difficulties, which could negatively impact reentry (e.g., Cloitre et al., 2009; Min, Farkas, Minnes, & Singer, 2007). The relationship between childhood maltreatment and coping self-efficacy has not been addressed. This study found that childhood …

Characterization Of Cyclic-Di-Gmp Signaling With The Lyme Spirochete, Borrelia Burgdorferi, Jessica Kostick

Theses and Dissertations

Lyme disease is a tick-borne infection caused by Borrelia burgdorferi, B. garinii, and B. afzelii. These spirochetes experience environmental fluctuations as they are passed between mammalian and Ixodes tick hosts throughout their enzootic cycle. Recent studies have suggested cyclic diguanylate (c-di-GMP), a ubiquitous secondary messenger, is a key modulator of B. burgdorferi adaptive responses and may play a significant role in cycle progression. In this study, we examined the impact of the sole diguanylate cyclase (Rrp1), c-di-GMP binding proteins (PlzA and PlzB), and HD-GYP-containing phosphodiesterase (PdeB) in disease establishment of both murine and Ixodes tick systems. Strains harboring targeted gene …

The Use Of Targeted Charge-Reversal Nanoparticles (Tcrns) To Investigate Nuclear Delivery Of Fluorescent Agents To Cancer Cells: Implications For Novel Prostate And Breast Cancer Therapy, Mario Dance

Theses and Dissertations

Nanotechnology has recently emerged as a strong contributor toward research efforts to develop targeted systems of drug delivery in cancer therapy. Our work investigates the therapeutic potential of Targeted Charge-Reversal Nanoparticles (TCRNs), a novel nanoparticle with in vitro evidence of nuclear drug delivery. Using M12 prostate cancer cells, MDA-MB-231 breast cancer cells, and modified derivatives of these cell lines, we investigated the ability of Folic Acid-tagged TCRNs to deliver Nile Red and Dimethyl Indole Redfluorescent (DiR) fluorescent dyes to the nucleus of cells using confocal microscopy and in vivo biphontonic imaging using Xenogen® Technology. Confocal imaging with the SCP28 derivative …

The Regulation Of Tonb-Dependent Transporters In Neisseria Gnorrhoeae, Aimee Hollander

Theses and Dissertations

Neisseria gonorrhoeae is an obligate human pathogen that causes the common sexually- transmitted infection, gonorrhea. Gonococcal infections cause significant morbidity, particularly among women, as the organism ascends to the upper reproductive tract, resulting in pelvic inflammatory disease, ectopic pregnancy and infertility. Antibiotic resistance rates have risen dramatically, leading to severe restriction of treatment options for gonococcal disease. Gonococcal infections do not elicit protective immunity nor is there an effective vaccine to prevent the disease. Thus, further characterization of expression, function and regulation of surface antigens could lead to better treatment and prevention modalities in the future. N. gonorrhoeae express a …

Gene Expression In The Right Ventricle During Development Of Pulmonary Hypertension, Jennifer Drake

Theses and Dissertations

Pulmonary arterial hypertension (PAH) is a disease of the lung vessels that causes severe effects on the right ventricle of the heart; ultimately, most patients with severe PAH die as a result of right heart failure. However, little is known about the causes of right heart failure. Here, we describe a pattern of gene expression that differs between the normal rat left ventricle (LV) and right ventricle (RV). These genes are known to be involved in the development of the heart as well as adaptations to the heart during stress. This gene expression pattern is used as a baseline to …

The Abundance And Infection Status Of Anopheles Spp. Mosquitoes At Three Sites In Loudoun County, Northern Virginia, Priya Krishnan

Theses and Dissertations

Malaria is a re-emerging infectious disease with approximately half of the world's population at risk. In the US, since the 1950’s the Center for Disease Control (CDC) has been reporting between 1,000 and 1,500 cases of malaria every year. A majority of these cases were among US travellers and were attributed to Plasmodium falciparum. In August 2002, two cases of human malaria due to Plasmodium vivax were reported in Loudoun County, Northern Virginia. The Center for Disease Control and Prevention concluded that these cases were acquired locally. This was because of an absence of other risk factors such as international …

Characterizing The Distribution Of Planktonic Fecal Bacteria In The James River, Richmond, Virginia, John Furry

Theses and Dissertations

Surface waters containing fecal bacteria present significant public health risks. Understanding the sources of and factors affecting the distribution of fecal-indicating bacteria is necessary to predict potential illnesses more effectively. This thesis presents two studies on the distribution of fecal bacteria in the James River through Richmond, Virginia. Chapter 1 describes nearly 11 years of water quality, climate, and hydrologic data that occurred with changes in Escherichia coli concentrations, concluding that Richmond contributes significant quantities of fecal bacteria to the James River, and that the distribution of these bacteria varies seasonally. Chapter 2 details the development of Polymerase Chain Reaction …

Development And Evaluation Of A Multiplex Suspension Array Protocol For The Detection Of Enteric Pathogens From Clinical Specimens, Carol Walters

Theses and Dissertations

Foodborne illnesses are a significant public health challenge in the United States, with an estimated 9.4 million illnesses annually attributed to the consumption of contaminated food, of which 59% are estimated to be caused by viruses, 39% by bacteria and 2% by parasites. Timely detection and identification of the pathogens causing foodborne outbreaks is vital for the implementation of outbreak control strategies, allowing public health officials to prevent additional illnesses and maintain confidence in the food supply. Public health laboratories employ a variety of traditional and molecular testing techniques to identify foodborne outbreak etiologic agents. One technology is the Luminex …

Cumulative Risks To Eastern Oysters, Crassostrea Virginica In The James River, Va, Vrushali Lele

Theses and Dissertations

In an effort to apply Cumulative Risk Assessment (CRA) as developed by the U.S. EPA, the present study investigates the cumulative risks to Eastern oysters due to multiple stressors such as salinity, temperature and oxygen and carbon dioxide. I also compared the effectiveness of the Hazard Quotient Method (HQ) in CRA. Ambient conditions in the James River, VA were obtained from the Virginia DEQ database and respiratory responses were estimated using values from the literature. The multiple environmental stresses are evaluated using a probabilistic analysis that combines the environmental conditions. It was concluded that salinity was the most influential stressor …

Accelerating Finite State Projection Through General Purpose Graphics Processing, Thomas Trimeloni

Theses and Dissertations

The finite state projection algorithm provides modelers a new way of directly solving the chemical master equation. The algorithm utilizes the matrix exponential function, and so the algorithm’s performance suffers when it is applied to large problems. Other work has been done to reduce the size of the exponentiation through mathematical simplifications, but efficiently exponentiating a large matrix has not been explored. This work explores implementing the finite state projection algorithm on several different high-performance computing platforms as a means of efficiently calculating the matrix exponential function for large systems. This work finds that general purpose graphics processing can accelerate …

Screening For Cytomegalovirus During Pregnancy, Stuart P. Adler

Pediatrics Publications

The epidemiology and pathogenesis of CMV infections among pregnant women have been intensely studied over the last three decades. This paper highlights recent developments that make either universal or limited serologic screening for CMV during pregnancy potentially attractive. The developments include an understanding of the pathogenesis of CMV infections, a knowledge of high-risk women, the availability of accurate methods for the serologic diagnosis of a primary CMV infection using either single or serial blood samples, accurate methods for the diagnosis of fetal infection via amniotic fluid, sensitive fetal and placental indicators for neonatal outcomes, and the availability of potentially effective …

Individual Physician Versus Team-Based Medical Encounters: Maximizing The Efficiency Of A Medical Relief Service In Rural Honduras, Rachel Whitney, Michael P. Stevens, Gonzalo M. L. Bearman

Internal Medicine Publications

Background. For several years, the Virginia Commonwealth University (VCU) Department of Internal Medicine has traveled to the towns of La Hicaca and Coyoles in rural Honduras. In 2010, a new encounter method was employed during the brigade in Coyoles. Objectives. To examine the differences in clinical encounters and adherence with chronic diseases and public health screening between the traditional and team-based encounter methods. Methods. Chi-square analysis was used to determine statistical significance between encounter methods over several variables used in the standard interview form. Results. 314 patients were interviewed using the team-based approach, and 153 patients were interviewed with the …

Virginia Commonwealth University Graduate And Professional Programs Bulletin Courses [2011], Virginia Commonwealth University

VCU Bulletins

No abstract provided.

Influence Of Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodiafiltration On The Disposition Of Doripenem, Iolanda Cirillo, Nicole Vaccaro, Dainius Balis, Rebecca Redman, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg intravenous infusion of doripenem were assessed in dialysis-dependent subjects with stage 5 chronic kidney disease undergoing continuous renal replacement therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were also assessed (n = 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysis-dependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater, respectively, than those …

Intravaginal Cytomegalovirus (Cmv) Challenge Elicits Maternal Viremia And Results In Congenital Transmission In A Guinea Pig Model, Megan J. Olejniczak, K Yeon Choi, Michael Mcvoy, Xiaohong Cui, Mark R. Schleiss

Pediatrics Publications

Background The objective of this study was to compare intravaginal (ivg) and subcutaneous (sc) administration of the guinea pig cytomegalovirus (GPCMV) in pregnant and non-pregnant guinea pigs. These studies tested the hypotheses that ivg infection would elicit immune responses, produce maternal viremia, and lead to vertical transmission, with an efficiency similar to the traditionally employed sc route.

Results Four groups of age- and size-matched guinea pigs were studied. Two groups were pregnant, and two groups were not pregnant. Animals received 5x105 plaque-forming units (PFU) of a GPCMV reconstituted from an infectious bacterial artificial chromosome (BAC) construct containing the full-length GPCMV …

The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker

Theses and Dissertations

Periodontitis affects 10 to 15 percent of most adult populations and can contribute to numerous systemic diseases. Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized prime causative agent in periodontitis. Studies have shown a number of small non-coding RNAs (sRNAs) have been related to bacterial virulence. Many of these sRNAs require the facilitation of the bacterial Sm-like protein, Hfq, for optimum function. Hfq is a RNA chaperone involved in RNA stability, sRNA function, and polyadenylation. Mutants lacking in Hfq often show pleiotropic phenotypes, although the extent and severity of hfq null phenotypes is often species-specific. Hfq has been encoded …

Acquired Cytogenetic Changes In Adult Twins Discordant For A History Of Childhood Sexual Abuse, Jenni Brumelle

Theses and Dissertations

The primary study aim was to evaluate the latent biological effect of childhood sexual abuse (CSA) on adults by quantifying acquired cytogenetic changes and cortisol levels in identical twins who were discordant (N=22) or concordant (N=2) for a history of CSA. Although the difference scores for cortisol values between discordant identical co-twins were not significantly different from zero, a trend was observed for the twins exposed to intercourse, the most severe form of CSA, to have a blunted cortisol awakening response. Acquired cytogenetic changes were assessed by scoring telomere lengths and somatic cell abnormality frequencies via a cytokinesis-block micronucleus (MN) …

Synthesis, Screening And Cocrystallization Of Adenosine Based Inhibitors With Methyltransferases, Ermc' And Ksga, Matthew Baker

Theses and Dissertations

Antibiotic resistance threatens to throw mankind back into an era when infectious disease was the predominant cause of death. In an effort to mitigate this danger, we targeted ErmC’ and KsgA. Both methylate N6-adenosine of ribosomal RNA, though each serve different roles in their bacterial host. ErmC’ dimethylates A2058 on 23S rRNA, conferring resistance to MLSB antibiotics (macrolides, lincosamides, streptogramin B). KsgA aids in ribosome assembly, binding inactive 30S until dimethylating A1518/A1519 of 16S rRNA. Like most methyltransferases, ErmC’ and KsgA use cofactor S-adenosylmethionine (SAM) as their methyl source, which binds adjacent to their specific adenosine substrate. ErmC’ inhibitors could …

Genetic Manipulation Of The Relapsing Fever Spirochete Borrelia Hermsii Permits Novel Investigation Into The Role Of Factor H Binding In Borrelial Virulence, Lindy Fine

Theses and Dissertations

Borrelia hermsii, an etiologic agent of tick-borne relapsing fever, binds negative complement regulator factor H (FH) via its FhbA protein. Direct demonstration of the role of FhbA in the disease process has been hindered by the lack of genetic manipulation systems for the relapsing fever Borrelia. Here, we demonstrate successful generation of a B. hermsii strain YOR fhbA deletion mutant (Bh YORΔfhbA) that constitutively produces green fluorescent protein (GFP). Genetic manipulation did not affect growth rate or plasmid composition. Bh YORΔfhbA lost factor H-binding and C3b-inactivation capabilities, but retained resistance to killing in human serum and infectivity in mice. Stable …

Inferential Methods For High-Throughput Methylation Data, Maria Capparuccini

Theses and Dissertations

The role of abnormal DNA methylation in the progression of disease is a growing area of research that relies upon the establishment of sound statistical methods. The common method for declaring there is differential methylation between two groups at a given CpG site, as summarized by the difference between proportions methylated db=b1-b2, has been through use of a Filtered Two Sample t-test, using the recommended filter of 0.17 (Bibikova et al., 2006b). In this dissertation, we performed a re-analysis of the data used in recommending the threshold by fitting a mixed-effects ANOVA model. It was determined that the 0.17 filter …

Do General, Community Hospitals Compete By Specializing In High Volume, High Revenue-Generating Service Lines?, Nancy J. Muller

Theses and Dissertations

To determine if general, community hospitals show evidence of specializing in the nation's six highest volume, highest revenue-generating service lines, 2003-2007 data of hospitals throughout Florida, Virginia, and Nevada were analyzed using backward deletion, stepwise regression. Service lines selected for study were cardiac surgery, cardiology, invasive cardiology, orthopedics, labor and delivery, and pulmonary services. Results do show evidence of specialization, but characteristics of hospitals vary by service line. Findings suggest that the general, community hospital, traditionally a full-service provider, may be undergoing transformation including specialization. The study demonstrates the usefulness of studying specialization at the service line level.

Handling External Events Efficiently In Gillespie's Stochastic Simulation Algorithm, Brad Geltz

Theses and Dissertations

Gillespie's Stochastic Simulation Algorithm (SSA) provides an elegant simulation approach for simulating models composed of coupled chemical reactions. Although this approach can be used to describe a wide variety biological, chemical, and ecological systems, often systems have external behaviors that are difficult or impossible to characterize using chemical reactions alone. This work extends the applicability of the SSA by adding mechanisms for the inclusion of external events and external triggers. We define events as changes that occur in the system at a specified time while triggers are defined as changes that occur to the system when a particular condition is …

The Expression Of Matrix Metalloproteinase-9 And -2 In Olfactory Injury And Recovery, Stephen Bakos

Theses and Dissertations

The olfactory system has the remarkable capacity for neurogenesis following injury. However, the molecular mechanisms important for reinnervation of the olfactory bulb (OB) remain unknown. The matrix metalloproteinases (MMPs) are important components in many central nervous system (CNS) injury paradigms, yet remain unexplored in olfactory injury and recovery. To address the role of MMPs, the temporal expressions of MMP-9 and MMP-2 were examined in 3 olfactory injury models: nerve transection (NTx), methyl bromide gas (MeBr) exposure, and nerve transection with Teflon barrier (NTx-TB). Each injury model represents a different degree of olfactory injury and neuronal recovery. In NTx, sensory axons …

B Cell Adam10 Activity Is Increased By Kainate Receptor Activation: Potential Role Of This Pathway In Th2 Immunity And Cancer, Jamie Sturgill

Theses and Dissertations

CD23 has long been appreciated to be a natural, negative regulator of IgE synthesis. This understanding is due in part to animal models in which CD23 deficient or CD23 transgenic animals display exacerbated or reduced IgE levels respectively. Interestingly, CD23 is susceptible to proteolytic cleavage from the cell surface. When this occurs, CD23 loses its regulatory capability and the solubilized form can lead to pro-inflammatory events through its cytokinergic activity on macrophages. Thus, targeting this specific cleavage would be beneficial to the control of allergic disease by stabilizing CD23 at the cell surface. Inhibitor studies performed by our group as …

Characterization And Crystallization Of The Mycobacterium Tuberculosis Trmd, Zohal Hamidi

Theses and Dissertations

One third of the world’s population is affected by Tuberculosis (TB), a disease caused by infection with Mycobacterium tuberculosis (MtB). The emergence of multidrug-resistant MtB makes this disease a major public health concern. New agents are needed to treat TB infections in a manner that circumvents existing pathways of resistance. One strategy is to target the organism at the translational level by inhibiting vital modifications of RNA. One gene responsible for these modifications is the tRNA (guanosine-1)-methyltransferase, trmD, which has been shown to be essential in several bacteria. The eukaryotic and bacterial m1G methyltransferases are structurally dissimilar, making this enzyme …

Molecular Mechanisms Involved Involved In The Interaction Effects Of Hcv And Ethanol On Liver Cirrhosis, Ryan Fassnacht

Theses and Dissertations

The leading causes of liver disease are Hepatitis C virus infection and chronic alcohol abuse. Alcohol accelerates liver disease in HCV but the mechanisms are poorly understood. The identification of molecular gene expression profiles on human liver tissue was performed using microarrays. Samples were obtained from alcoholic-cirrhotic, HCV-cirrhotic, HCV/alcohol-cirrhotic and control non-cirrhotic liver tissue. Probe set expression summaries were calculated using RMA. Probe set level linear models were fit where probe set expression was modeled by HCV status, alcohol status, and the interaction between HCV and Alcohol. HCV cirrhosis was associated with up-regulation of genes related to viral and immune …

Children Adopted Internationally Examining Developmental Status At Arrival And Six Month Follow Up, Ann Mccormick

Theses and Dissertations

In the past 5 years, almost 100,000 children have been internationally adopted. Research suggests that many of these children have growth and developmental delays, but few large scale studies have been completed. In the current study data obtained from a restrospective chart review of 534 children followed in the International Adoption Clinic at Cincinnati Children’s Hospital Medical Center between 1999 and 2007 was analyzed. Prevalence of developmental delays and sensory processing issues initially and after 6 months in country, the relationship of delays/issues with previously identified risk factors, and the frequency of recommendations for early intervention (EI) and therapy services …

Ex Vivo Expansion Of Tumor-Specific T Cells With Sequential Common Gamma Chain Cytokines Render Them Refractory To Mdsc Upon Adoptive Immunotherapy., Debasmita Basu

Theses and Dissertations

Myeloid derived suppressor cells (MDSCs) are heterogeneous population of immature cells at various stages of differentiation, characterized by the presence of CD11b and Gr1 in mice. They are major contributors of the tumor-induced immune suppression against the tumors. So far, various strategies have been introduced to overcome the endogenous MDSCs. Most of these approaches rely on the elimination of MDSCs and it is not clear whether tumor-reactive T cells may be differentiated towards phenotypes that are refractory to MDSCc. Our laboratory has previously shown that high affinity T cells derived from tumor-sensitized wild-type FVB mice and expanded ex vivo with …