Medicine and Health Sciences Commons^™

Virginia Dental Journal (Vol. 89, No. 4, 2012)

Virginia Dental Journal

No abstract provided.

Public Reporting As A Communication Tool To Aid Vulnerable Consumers In Healthcare Decisions: What Do We Know?, Daniel R. Longo, Barbara A. Wright

VCU Libraries Faculty and Staff Presentations

Background/Introduction:

There is tremendous variation in quality, healthcare service utilization and disparities experienced by the poor, certain minorities, and other priority populations. Public reporting is identified as one method of bringing these differences to light and by informing consumers through documented comparison of provider performance to influence change and encourage improvement in healthcare. The federal Accountable Care Act has the stated mandate “to improve the dissemination of measures of healthcare quality and resource use, (and) to build the science of public reporting.” However, early studies on the design and use of consumer reports cite the public’s confusion and lack of …

Mekk1-Mkk4-Jnk-Ap1 Pathway Negatively Regulates Rgs4 Expression In Colonic Smooth Muscle Cells, Yonggang Zhang, Fang Li, Shu Liu, Hong Wang, Sunila Mahavadi, Karnam S. Murthy, Kamel Khalili, Wenhui Hu

Physiology and Biophysics Publications and Presentations

Background

Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1β is mediated by the activation of NFκB signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. Here we investigate the effect of the c-Jun N-terminal kinase (JNK) pathway on Rgs4 expression in rabbit colonic smooth muscle cells.

Methodology/Principal Findings

Cultured cells at first passage were treated with or without IL-1β …

Fret-Based Localization Of Fluorescent Protein Insertions Within The Ryanodine Receptor Type 1, Shweta A. Raina, Jeffrey Tsai, Montserrat Samsó, James D. Fessenden

Physiology and Biophysics Publications and Presentations

Fluorescent protein (FP) insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM) maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET) measurements were used to localize green fluorescent protein (GFP) insertions within the ryanodine receptor type 1 (RyR1), a large intracellular Ca2+ release channel that plays a key role in skeletal muscle excitation contraction coupling. A series of full-length …

The Molecular Mechanism By Which Pip2 Opens The Intracellular G-Loop Gate Of A Kir3.1 Channel, Xuan-Yu Meng, Hong-Xing Zhang, Diomedes E. Logothetis, Meng Cui

Physiology and Biophysics Publications and Presentations

Abstract

Inwardly rectifying potassium (Kir) channels are characterized by a long pore comprised of continuous transmembrane and cytosolic portions. A high-resolution structure of a Kir3.1 chimera revealed the presence of the cytosolic (G-loop) gate captured in the closed or open conformations. Here, we conducted molecular-dynamics simulations of these two channel states in the presence and absence of phosphatidylinositol bisphosphate (PIP₂), a phospholipid that is known to gate Kir channels. Simulations of the closed state with PIP₂ revealed an intermediate state between the closed and open conformations involving direct transient interactions with PIP₂, as well as …

Normal-Mode-Analysis-Guided Investigation Of Crucial Intersubunit Contacts In The Camp-Dependent Gating In Hcn Channels, Farzana Marni, Shengjun Wu, Gaurav M. Shah, Xin-Ping Xu, Amber R. Hackett, Changan Xie, Sabisha Shrestha, Lin Liu, Qinglian Liu, Lei Zhou

Physiology and Biophysics Publications and Presentations

Abstract

Protein structures define a complex network of atomic interactions in three dimensions. Direct visualization of the structure and analysis of the interaction potential energy are not straightforward approaches to pinpoint the atomic contacts that are crucial for protein function. We used the tetrameric hyperpolarization-activated cAMP-regulated (HCN) channel as a model system to study the intersubunit contacts in cAMP-dependent gating. To obtain a systematic survey of the contacts between each pair of residues, we used normal-mode analysis, a computational approach for studying protein dynamics, and constructed the covariance matrix for C-α atoms. The significant contacts revealed by covariance analysis …

The Interdomain Linker Of Aav-2 Rep68 Is An Integral Part Of Its Oligomerization Domain: Role Of A Conserved Sf3 Helicase Residue In Oligomerization, Francisco Zarate-Perez, Martino Bardelli, John W. Burgner Ii, Maria Villamil-Jarauta, Kanni Das, Demet Kekilli, Jorge Mansilla-Soto, R. Michael Linden, Carlos R. Escalante

Physiology and Biophysics Publications and Presentations

The four Rep proteins of adeno-associated virus (AAV) orchestrate all aspects of its viral life cycle, including transcription regulation, DNA replication, virus assembly, and site-specific integration of the viral genome into the human chromosome 19. All Rep proteins share a central SF3 superfamily helicase domain. In other SF3 members this domain is sufficient to induce oligomerization. However, the helicase domain in AAV Rep proteins (i.e. Rep40/Rep52) as shown by its monomeric characteristic, is not able to mediate stable oligomerization. This observation led us to hypothesize the existence of an as yet undefined structural determinant that regulates Rep oligomerization. In this …

Predictors Of Carbapenem Resistant Gram-Negative Bacteria In A Consortium Of Academic Medical Center Hospitals, Mera Ababneh

Theses and Dissertations

Background: Gram-negative resistance is a growing problem worldwide. It is generally believed that rates of resistant bacteria within a hospital are a function of antibiotic use, resistant organisms brought into the hospital, infection control efforts, and underlying severity of patient illness. The relative contribution of each to a particular resistance phenotype is unclear. P. aeruginosa is responsible for many hospital acquired infections and it may become resistant to carbapenems. In addition, newer threats to the future utility of the carbapenems are carbapenemase-producing K. pneumoniae Purpose: To determine if there is an association between the volume and composition of antibiotic use, …

Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook

Theses and Dissertations

The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and …

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …

Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra

Theses and Dissertations

DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …

Biobehavioral Correlates In Fibromyalgia, Ann Trivigno Mcnallen

Theses and Dissertations

Introduction: Fibromyalgia (FMS) is a chronic pain syndrome characterized by non-restorative sleep, and fatigue. Over 75% of individuals with FMS complain of poor sleep quality and fatigue. These have been ranked by patients with FMS as having great impact on quality of life. A literature review suggested that poor sleep quality may be a predictor of increased stress and FMS symptom onset in those affected. However, no experimental studies have demonstrated a causal relationship between poor sleep and stress in people with FMS. Methods: Using a single stage cross-sectional design, the primary study aim was to compare 25 women with …

A Comparison Of Maximal Exercise Responses Among Patients With A Total Artificial Heart, A Left Ventricular Assist Device, Or Advanced Heart Failure, Justin M. Canada

Theses and Dissertations

The purpose of this study was to evaluate graded exercise responses to treadmill exercise in patients with a total artificial heat (SynCardia, Tucson, AZ). Additionally, this study sought to compare the exercise response in total artificial heart (TAH) patients to both advanced heart failure (HF) patients on medical management only and HeartMate II (Thoratec Corp., Pleasanton, CA) left‐ventricular assist device (HMII) patients. For patients with biventricular heart failure the TAH is a viable option to bridge patients until transplant becomes available. Its demonstrated improvement in mortality and increasing usage necessitates a shift in focus to quality of life in the …

The Role Of Fyn And B-Cell Expressed Adam10 In Early B Cell Development, Germinal Center Formation And Terminal B Cell Differentiation, Natalia Chaimowitz

Theses and Dissertations

In these studies we sought to determine the role of Fyn kinase and ADAM10 in B cell biology. A disintegrin and metalloproteinase 10 (ADAM10) is a zinc dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. In particular, ADAM10 has been identified as a key regulator of lymphocyte development. Here we report that ADAM10 is dispensable for early B cell development within the bone marrow. However, deletion of ADAM10 from all peripheral B cells or in post-switch cells leads to severe …

Group I Metabotropic Glutamate Receptors On Selective Cellular Subtypes In Epileptogenic Malformed Cortex, William Bruch

Theses and Dissertations

Cortical malformations from altered development are common causes of human epilepsy. The cellular mechanisms responsible for the epileptic state of cortex remain unclear and a significant portion of these cases do not respond to treatment. Previous electrophysiological recordings in the Jacobs lab in a rat polymicrogyria model indicated an increased response to group I metabotropic glutamate receptor agonists in the region adjacent to the malformation (PMZ). In addition there was a novel response in low threshold spiking (LTS) interneurons via mGluR5 activation. To determine whether cell specific expression of these receptors was altered in malformed cortex immunohistochemical stains were performed …

The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall

Theses and Dissertations

Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine …

Virginia Dental Journal (Vol. 89, No. 1, 2012)

Virginia Dental Journal

No abstract provided.

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …

Effectiveness Of Sensory Integration And Behavioral Interventions On Nonengagement In Preschool Aged Children, Tiffany Kuyper

Theses and Dissertations

Abstract EFFECTIVENESS OF SENSORY INTEGRATION AND BEHAVIORAL INTERVENTIONS ON NONENGAGEMENT IN PRESCHOOL AGED CHILDREN By Tiffany Ann Kuyper, OTR/L A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Occupational Therapy at Virginia Commonwealth University Virginia Commonwealth University, 2012 Director: Marie Anzalone ScD, OTR, FAOTA This single subject pilot study explored a combination of sensory-based interventions and behavioral interventions in a preschool aged child identified with Sensory Over-Responsivity (SOR). Children often display nonengagement associated with escaping and avoiding tactile and/or vestibular information because they perceive sensory input as negative or aversive. The subject …

Factors Influencing Pharmacists’ Decision To Report Adverse Events Related To Dietary Supplements, Ali M. Alhammad

Theses and Dissertations

Background: The increasing consumption of dietary supplements (DS) has drawn the attention of regulatory agencies, researchers and healthcare professionals. The US Food and Drug Administration (FDA) does not require premarketing assessment of DS considering them safe unless proven otherwise. However, the reporting rate of DS adverse events (DS-AE) is low. Objective: To describe pharmacists’ attitudes and knowledge of DS and DS information resources, and to determine the importance of selected attributes in pharmacists’ decisions to report a DS-AE. Methods: A convenience sample of practicing pharmacists in Virginia was surveyed using a web-based self-administered questionnaire. A conjoint analysis exercise was developed …

Role Of Extracytoplasmic Function Sigma Factors In Porphyromonas Gingivalis, Suhasini Yanamandra Sai

Theses and Dissertations

Porphyromonas gingivalis is a major etiological agent that is responsible for the cause and progression of periodontal diseases. The bacterium is exposed to various environmental conditions and oxidative stress conditions while it is in the oral cavity. So, P. gingivalis should have an efficient regulatory system in order to adjust and survive in the oral cavity. But little is known about the regulatory mechanisms that help the bacteria to survive in the oral cavity. So, it is essential to understand and characterize these regulatory mechanisms. The response and adaptation of P. gingivalis to environmental stress conditions occur at the level …

Designing Direct And Indirect Factor Xa Inhibitors, Rami Al-Horani

Theses and Dissertations

Anticoagulants are the basis for treatment and prevention of thrombotic diseases. The currently available medicines are associated with a wide range of adverse reactions that mandates developing new anticoagulants. Several lines of evidence support the superiority of factor Xa (FXa) as a promising target to develop novel anticoagulants. This work focuses on the design of direct and indirect FXa inhibitors using an interdisciplinary approach. As indirect FXa inhibitors, a focused library of tetrasulfated N–arylacyl tetrahydroisoquinoline (THIQ) nonsaccharide allosteric antithrombin activators was designed, synthesized, and biochemically evaluated to establish their structure–activity relationship (SAR). An N–arylacyl THIQ analog having carboxylate at position–3, …

Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …

Development Of Dual-Pathway Inhibitors Of Raf/Mek/Erk And Pi3k/Akt Signaling Pathways., Sasha Fraser

Theses and Dissertations

In the present study, we designed a new chemical template that contains an oxindole moiety as potential dual-pathway inhibitors of the Raf/MEK/ERK and PI3K/Akt signaling pathways. The design hypothesis is to evaluate whether the oxindole ring system will approximately orient functional groups in a similar manner to the thiazolidinedione moiety, and thus maintain biological activity as dual-pathway inhibitors of the Raf/MEK/ERK and PI3K/Akt signaling pathways. Furthermore, the oxindole ring will provide the flexibility to allow the introduction of various substituents on the oxindole moiety, thereby facilitating comprehensive SAR studies to further explore the biological activity.

Age Dependent Spatial Characteristics Of Epileptiform Activity In Malformed Cortex, L. Andrew Bell

Theses and Dissertations

Developmental cortical malformations are a major cause of intractable seizures. Determining the location and timing of susceptibility for epileptiform activity is critical to identifying what mechanisms contribute to epileptogenesis in any model. Using the freeze lesion rat model of polymicrogyria, we have identified, in lesioned cortex, these two aspects of epileptogenesis. Previous studies have demonstrated that epileptiform activity cannot be evoked prior to postnatal day (P) 12, but the malformed cortex is more susceptible to seizures as early as P10. An increase in excitatory afferents to the epileptogenic zone occurs before the onset of network epileptiform activity. Whether or not …

Medication-Related Problems In Older Adults: A Focus On Underuse Of Warfarin And Warfarin-Antibiotic Interactions, Parinaz K. Ghaswalla

Theses and Dissertations

The work presented in this dissertation focuses on two important medication-related problems in older adults, that is, untreated indication and drug-drug interactions, specifically with respect to a high-risk medication such as warfarin. Warfarin is a challenge to use in clinical practice due to its narrow therapeutic index, variability in dose-response and its interactions with numerous foods and drugs. This dissertation presents the research from two projects. In the first project the prevalence and predictors of warfarin use in nursing home (NH) residents with atrial fibrillation (AF), and use of secondary stroke prevention strategies was determined, in order to understand the …

Development Of A Novel Approach To Assess Qualitative And Quantitative Dynamics Associated With The Subcutaneous Or Intramuscular Administration Of Pharmaceuticals And Associated Parenteral Delivery Systems, Eric Edwards

Theses and Dissertations

There has been a significant increase in the number of injectable pharmaceutical products over the last decade that have been incorporated into unique delivery systems such as pen injectors, auto-injectors, or pre-filled syringes. The advancement of these delivery systems and the paradigm shift towards administration of injectables in the out-of-hospital or home setting have introduced variables that can affect the bioavailability of injectable drugs and potential pharmacologic outcomes. An approach that allows for the qualitative and quantitative dispersion assessment of an injectable at the moment of tissue deposition coupled with an assessment of systemic exposure parameters could provide substantial information …

The Determinants Of A Nurse's Discretionary Decision To Respond To Situations That Place Patients At Risk For Safety Events But Requires A Response That Is Beyond The Scope Of Nursing Practice, Kathy Baker

Theses and Dissertations

A nurse’s contribution to patient safety in regards to early detection of issues in the clinical setting is undisputed (Redman, 2008). If these patient situations require a response that is beyond the scope of nursing practice, in most instances nurses are not sanctioned to intervene without physician consultation (Gaba, 2000). The evidence in the nursing literature does suggest that some nurses exercise professional discretion and are, at times, making the decision to initiate interventions independently (Benner, Hooper-Kyriakidis, & Stannard, 1999; Hutchinson, 1990; Tiffany, Cruise, & Cruise, 1988). The focus of this inquiry was to examine the determinants of a nurse’s …

Response To And Recovery From Endotracheal Suctioning In Preterm Infants Using Routine Versus Four-Handed Care, Sharon Cone

Theses and Dissertations

Neonatal Intensive Care Units have experienced profound advances in technology and treatment modalities over the last two decades. Infants born at the edge of viability are now surviving despite prolonged hospitalizations. These infants born preterm are prone to a high degree of stress from life sustaining and routine interventions. Much focus has been directed toward addressing noxious environmental factors such as noise, light, and infectious disease; however, little has been done to examine the stress experienced by the professional caregiver who work in these environments. Environmental press theory, which focuses on the interplay between human beings and their surroundings, is …

Caring For A Preterm Infant During The First Six Months Post Nicu Discharge: A Mother’S Perspective, Lois Phillips-Pula

Theses and Dissertations

Overview There are numerous studies in the current literature focusing on the intense emotions experienced by parents, following the birth of a preterm infant, (i.e., born prior to 37 weeks gestational age [GA]). Research findings have helped us understand the fear and anxiety they feel while attempting to navigate the neonatal intensive care unit (NICU) environment. What happens in those early weeks and months at home after discharge, however, is surprisingly absent from the literature. It is well known that preterm infants are readmitted to the hospital during the first few months after discharge at a rate of 10% - …