Medicine and Health Sciences Commons^™

Interaction Of Glycolysis And Mitochondrial Respiration In Metabolic Oscillations Of Pancreatic Islets, Richard Bertram, Leslie S. Satin, Morten Gram Pedersen, Dan S. Luciani, Arthur Sherman

Pharmacology and Toxicology Publications

Abstract

Insulin secretion from pancreatic β-cells is oscillatory, with a typical period of 2–7 min, reflecting oscillations in membrane potential and the cytosolic Ca²⁺ concentration. Our central hypothesis is that the slow 2–7 min oscillations are due to glycolytic oscillations, whereas faster oscillations that are superimposed are due to Ca²⁺ feedback onto metabolism or ion channels. We extend a previous mathematical model based on this hypothesis to include a more detailed description of mitochondrial metabolism. We demonstrate that this model can account for typical oscillatory patterns of membrane potential and Ca²⁺ concentration in islets. It also …

Biophysical Characterization Of Anticoagulant Hemextin Ab Complex From The Venom Of Snake Hemachatus Haemachatus, Yajnavalka Banerjee, Rajamani Lakshminarayanan, Subramanian Vivekanandan, Ganesh Srinivasan Anand, Suresh Valiyaveettil, R. Manjunatha Kini

Biochemistry and Molecular Biology Publications

Abstract

Hemextin AB complex from the venom of Hemachatus haemachatus is the first known natural anticoagulant that specifically inhibits the enzymatic activity of blood coagulation factor VIIa in the absence of factor Xa. It is also the only known heterotetrameric complex of two three-finger toxins. Individually only hemextin A has mild anticoagulant activity, whereas hemextin B is inactive. However, hemextin B synergistically enhances the anticoagulant activity of hemextin A and their complex exhibits potent anticoagulant activity. In this study we characterized the nature of molecular interactions leading to the complex formation. Circular dichroism studies indicate the stabilization of β-sheet …

Enhanced Balance Associated With Coordination Training With Stochastic Resonance Stimulation In Subjects With Functional Ankle Instability: An Experimental Trial, Scott E. Ross, Brent L. Arnold, J. Troy Blackburn, Cathleen N. Brown, Kevin M. Guskiewicz

Kinesiology and Health Sciences Publications

Background

Ankle sprains are common injuries that often lead to functional ankle instability (FAI), which is a pathology defined by sensations of instability at the ankle and recurrent ankle sprain injury. Poor postural stability has been associated with FAI, and sports medicine clinicians rehabilitate balance deficits to prevent ankle sprains. Subsensory electrical noise known as stochastic resonance (SR) stimulation has been used in conjunction with coordination training to improve dynamic postural instabilities associated with FAI. However, unlike static postural deficits, dynamic impairments have not been indicative of ankle sprain injury. Therefore, the purpose of this study was to examine the …

Clomiphene, Metformin, Or Both For Infertility In The Polycystic Ovary Syndrome, Richard S. Legro, Huiman X. Barnhart, William D. Schlaff, Bruce R. Carr, Michael P. Diamond, Sandra A. Carson, Michael P. Steinkampf, Christos Coutifaris, Peter G. Mcgovern, Nicholas A. Cataldo, Gabriella G. Gosman, John E. Nestler, Linda C. Guidice, Phyllis C. Leppert, Evan R. Myers M.P.H.

Obstetrics and Gynecology Publications

Background

The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. Methods We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery.

Results

The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the …

Linkage Analysis Of A Model Quantitative Trait In Humans: Finger Ridge Count Shows Significant Multivariate Linkage To 5q14.1, Sarah E. Medland, Danuta Z. Loesch, Bogdan Mdzewski, Gu Zhu, Grant W. Montgomery, Nicholas G. Martin

Psychiatry Publications

The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds …

Application Of A Correlation Correction Factor In A Microarray Cross-Platform Reproducibility Study, Kellie J. Archer, Catherine I. Dumur, G. Scott Taylor, Michael D. Chaplin, Anthony Guiseppi-Elie, Geraldine Grant, Andrea Ferreira-Gonzalez, Carleton T. Garrett

Biostatistics Publications

Background Recent research examining cross-platform correlation of gene expression intensities has yielded mixed results. In this study, we demonstrate use of a correction factor for estimating cross-platform correlations.

Results In this paper, three technical replicate microarrays were hybridized to each of three platforms. The three platforms were then analyzed to assess both intra- and cross-platform reproducibility. We present various methods for examining intra-platform reproducibility. We also examine cross-platform reproducibility using Pearson's correlation. Additionally, we previously developed a correction factor for Pearson's correlation which is applicable when X and Y are measured with error. Herein we demonstrate that correcting for measurement …

Identification And Characterization Of Helper Phage Gene Products Involved In Mobilization Of Staphylococcal Pathogenicity Island Sapi1, Sandra Mckenzie Tallent

Theses and Dissertations

Staphylococcal pathogenicity island SaPI1 is excised from genomic DNA and extrachromosomal copies are amplified during the vegetative growth of staphylococcal phage 80α. The amplified genetic element is subsequently encapsidated and transduced at very high frequency. Previous studies have demonstrated that the transducing particles have virions with tails that appear identical to those of helper phage 80α but have smaller capsids, commensurate with the smaller genome of the SaPI (Lindsay et.al., 1998). The morphology of the transducing particles, coupled with the observation that the genomic sequence of SaPIl (GenBank U93688) does not reveal any obvious phage structural proteins, has led to …

The Association Between Adult Self-Reported Asthma & Potential Exposures To Asthma Triggers In Virginia Workplaces: An Ecological Study, Jeanette R. Bowman

Theses and Dissertations

Introduction: Work-related asthma (WRA) is thought to be the most common occupational lung disease in the U.S., but there is no standard case definition of WRA. Most states, including Virginia, do not require WRA diagnoses to be reported to health departments. At present, there is too little epidemiological data on WRA in Virginia to direct public health planning efforts. Objectives: The first objective of this study was to estimate potential exposure to workplace asthma triggers in each of Virginia's 35 health districts. The second objective was to examine associations at the health district level between workplace asthma triggers, other asthma …

Interactions Of Mtfabh With Its Substrates And Inhibitors Reveal Novel Mechanistic Insights, Sarbjot Singh Sachdeva

Theses and Dissertations

Tuberculosis emerged from its grave to be one of the deadliest diseases of the present time after recently developing a synergy with AIDS. A fatty acid condensing enzyme-mtFabH has been proposed to connect the key processes involved in biosynthesis of mycolic acids, an important component of mycobacterial cell wall. It condenses long acyl Coenzymes A (CoA; up to C20CoA) with malonyl Acyl Carrier Protein (ACP) to form the elongated β-ketoacyl-ACP which further undergoes rounds of elongation to form mero-mycolate branch of mature mycolic acids. Owing to its proposed central position in mycolic acid synthesis, mtFabH has attracted considerable attention as …

Telomerase Inhibition And Sensitization Of Breast Tumor Cells, Kennon R. Poynter

Theses and Dissertations

Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anticancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditions chemo- and radio-therapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities.While various …

The Substituted Pyrrole Jb-03-14 Induces Autophagic Cell Death And Growth Arrest In Breast Tumor Cells, Christopher Ryan Arthur

Theses and Dissertations

The use of chemotherapy in the treatment of cancer has stimulated the demand for better chemotherapeutic agents that are more potent at destroying tumor cell populations and more selective for the specific tumor versus normal host tissues. This project is directed at discovering new anti-tumor agents that are effective against breast cancer based on structures derived from marine organisms, specifically brominated pyrroles. We utilized an in vitro breast cancer model to study the effects of pyrroles on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that the substituted pyrrole JG-03-14 induces time dependent …

Peginterferon Alfa-2a And Ribavirin For 16 Or 24 Weeks In Hcv Genotype 2 Or 3, Mitchell L. Shiffman, Fredy Suter, Bruce R. Bacon, David Nelson, Hugh Harley, Richard Sola, Stephen D. Shafran, Karl Barange, Amy Lin, Ash Soman, Stefan Zeuzem

VCU Health Publications

Background

Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin.

Methods

We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 μg of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV …

Eltrombopag For Thrombocytopenia In Patients With Cirrhosis Associated With Hepatitis C, John G. Mchutchison, Geoffrey Dusheiko, Mitchell L. Shiffman, Maribel Rodriguez-Torres, Samuel Sigal, Marc Bourliere, Thomas Berg, Stuart C. Gordon, Fiona M. Campbell, Dickens Theodore, Nicole Blackman, Julian Jenkins, Nezam H. Afdhal

VCU Health Publications

Background

Eltrombopag is a new, orally active thrombopoietin-receptor agonist that stimulates thrombopoiesis. We evaluated its ability to increase platelet counts and facilitate treatment for hepatitis C virus (HCV) infection in patients with thrombocytopenia associated with HCV-related cirrhosis.

Methods

Seventy-four patients with HCV-related cirrhosis and platelet counts of 20,000 to less than 70,000 per cubic millimeter were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or placebo daily for 4 weeks. The primary end point was a platelet count of 100,000 per cubic millimeter or more at week 4. Peginterferon and ribavirin could then be initiated, with continuation …

Enhanced Care Assistant Training To Address The Workforce Crisis In Home Care: Changes Related To Job Satisfaction And Career Commitment, Constance L. Coogle, Iris A. Parham, Rita Jablonski, Jason A. Rachel

Virginia Center on Aging Publications

Changes in job satisfaction and career commitment were observed as a consequence of a geriatric case management training program focusing on skills development among personal care attendants in home care. A comparison of pretraining and posttraining scores uncovered a statistically signifi cant increase in Intrinsic Job Satisfaction scores for participants 18–39 years of age, whereas levels declined among the group of middle aged participants and no change was observed among participants age 52 and older. On the other hand, a statistically signifi cant decline in Extrinsic Job Satisfaction was documented over all participants, but this was found to be primarily …

Re-Imagining The Experience And Study Of Aging, Edward F. Ansello

Director's Editorials from Age in Action

A small group of Japanese and American gerontologists have been working together toward developing a gerontology curriculum that would help people to understand the experience of aging. The group suggested adding business, information technology/communication, and education to the curriculum. The group also acknowledged that a curriculum on aging should include a way to help those of us who are not old to understand the importance for many who are old of the search for the infinite, the true self, the oneness, the spirit, or the divine, at the core of life.

Health Care Reform And Family Caregivers, Edward F. Ansello

Director's Editorials from Age in Action

Health care reform is in the air. Family caregivers need recognition, reinforcement, and a reliable resource of assistance. They need for the Commonwealth to recognize that they are the bedrock of long-term care. Minimizing investment in family caregivers would short circuit any serious effort to improve the health status and care of older Virginians.

Fiscal Year Retrospective, Edward F. Ansello

Director's Editorials from Age in Action

The Virginia Center on Aging relies on the dedication and selflessness of so many collaborating groups, agencies, and individuals to make our work for older Virginians possible. Drawing from official and informal reports from the 2006-2007 fiscal year, we thank them deeply and look forward to continuing these partnerships.

Acute And Chronic Pain Challenges For Arthritis Patients In An Acute Care Setting, Janet M. Bykowski

Case Studies from Age in Action

Educational Objectives

1. Demonstrate the importance of chronic pain management in an acute care environment.

2. Discuss the special impact of co-morbidity of arthritis upon pain management intervention.

3. Provide education to clinicians, patients, and caregivers that would promote an interdisciplinary plan of care for acute and chronic concurrent pain management.

“Powerful Tools For Caregivers”: Teaching Skills That Reduce Stress And Increase Self-Confidence, Ed Rosenberg, Natasha Gouge

Case Studies from Age in Action

Educational Objectives

1. Describe caregiving stress and burnout symptoms and effects experienced by older caregivers.

2. Report implementation and evaluation of the “Powerful Tools for Caregivers” workshop, which is designed to increase knowledge and skills in caring for elders and reduce caregiver stress.

3. Suggest ways to alleviate caregiver burden at both micro and macro levels.

Teens Teaching Alzheimer’S Caregivers To Become Tech- Savvy: The Power Of Community And Intergenerational Partnerships, Ann Bruner Duesing, Marilyn Pace Maxwell

Case Studies from Age in Action

Educational Objectives

1. Describe a successful technology project for Alzheimer’s caregivers in rural, far southwest Virginia which recruited and trained teenagers to teach computer skills to Alzheimer’s caregivers and taught the teenagers about caregiving and the disease.

2. Identify barriers for Alzheimer’s caregivers to learning and using technology to assist and support them in their caregiving, and identify successful ways to address these barriers.

Pace: Program Of All-Inclusive Care For The Elderly, Laura R. Gadsby

Case Studies from Age in Action

Educational Objectives

1. Describe the Program of Allinclusive Care for the Elderly model of care for frail seniors with chronic health care needs.

2. Demonstrate how PACE benefits providers in the delivery of services.

3. Explain how the PACE concept complements Virginia’s Long Term Care Reform, as well as initiatives to develop further the PACE program in Virginia.

Expression Pattern Of Three-Finger Toxin And Phospholipase A2 Genes In The Venom Glands Of Two Sea Snakes, Lapemis Curtus And Acalyptophis Peronii: Comparison Of Evolution Of These Toxins In Land Snakes, Sea Kraits And Sea Snakes, Susanta Pahari, David Bickford, Bryan G. Fry, R. Manjunatha Kini

Biochemistry and Molecular Biology Publications

Background

Snake venom composition varies widely both among closely related species and within the same species, based on ecological variables. In terrestrial snakes, such variation has been proposed to be due to snakes' diet. Land snakes target various prey species including insects (arthropods), lizards (reptiles), frogs and toads (amphibians), birds (aves), and rodents (mammals), whereas sea snakes target a single vertebrate class (fishes) and often specialize on specific types of fish. It is therefore interesting to examine the evolution of toxins in sea snake venoms compared to that of land snakes.

Results

Here we describe the expression of toxin genes …

Probing The Outer Mouth Structure Of The Herg Channel With Peptide Toxin Footprinting And Molecular Modeling, Gea-Ny Tseng, Kailas D. Sonawane, Yuliya V. Korolkova, Mei Zhang, Jie Liu, Eugene V. Grishin, H. Robert Guy

Physiology and Biophysics Publications

Abstract

Previous studies have shown that the unusually long S5-P linker lining human ether a-go-go related gene’s (hERG’s) outer vestibule is critical for its channel function: point mutations at high-impact positions here can interfere with the inactivation process and, in many cases, also reduce the pore’s K⁺ selectivity. Because no data are available on the equivalent region in the available K channel crystal structures to allow for homology modeling, we used alternative approaches to model its three-dimensional structure. The first part of this article describes mutant cycle analysis used to identify residues on hERG’s outer vestibule that interact …

The Effect Of Pediatric Hospital Specialization On Patient Safety And Effectiveness Of Care, James Mitchell Harris Ii

Theses and Dissertations

Provider specialization is an area of interest in health care as patients, payers and policy makers are now demanding better performance and demonstrated proof of the benefits of specialization. While previously ignored in the specialization debate, now even the hospitals focusing on pediatric care (i.e. children's hospitals) are experiencing pressure to demonstrate their value. The current study attempts to answer the questions: do hospitals specializing in pediatric care provide better quality pediatric inpatient care; and do they do so for differing types of patient outcomes and across different levels of care complexity? Contingency Theory is used to develop and assess …

On The Binding Of N1-Substituted Tryptamines At H5-Ht6 Receptors, Abner Nyamwaro Nyandege

Theses and Dissertations

Serotonin was first discovered in the late 1940s as a vasotonic factor and is now considered a principal neurotransmitter in the nervous system. 5-HT6 receptors are one of the most recently identified members of the serotonin receptor family which consists of seven classes (5-HT1-5-HT7). 5-HT6 receptors are G-protein coupled, positively coupled to an adenylate cyclase second messenger system and are primarily found in the central nervous system (CNS). The exact functional role of 5-HT6 receptors has not been determined, but is implicated to have possible involvement in certain neuropsychiatric disorders and cognition. To investigate the functional role of these receptors, …

Adverse Anesthesia Outcomes: A Retrospective Study Of An Ambulatory Surgical Center Versus A Dental Office Setting, Gaurav Agarwal

Theses and Dissertations

Purpose: The purpose of this study was to compare the adverse events that occur with general anesthesia for dental rehabilitation between a hospital setting and dental clinic setting. Methods: A retrospective chart review was performed examining patients who had received dental rehabilitation with general anesthesia at the Virginia Commonwealth University Department of Pediatric Dentistry. Subjects were either treated in the Pediatric Dental Clinic or the Hospital Ambulatory Surgery Center (ASC) from July 2005 to December 2006. Anesthesia records of induction, intubation, maintenance, emergence and recovery were compared between the two settings.Results: There were a total of 422 charts reviewed with …

Analgesic Use In U.S. Emergency Departments For Patients Reporting Moderate To Severe Pain: Diagnosis And Select Patient Characteristics Influencing Narcotic Analgesic Prescribing Practices, Hassan Zakaria

Theses and Dissertations

Objective: This study aims to examine the relationship between emergency department patient encounter characteristics and narcotic analgesic prescribing practices in order to determine what patient characteristics, if any, influence the decision to prescribe narcotics.Methods: Cross sectional data on patients presenting to U.S. emergency departments from the 2003 and 2004 National Hospital Ambulatory Medical Care Survey were analyzed. Patients reporting moderate to severe pain were included in the sample and analysis. Chi square tests of significance were used to assess the association between individual demographic and encounter characteristics to narcotic prescription or administration. Separate multiple logistic regressions were then performed on …

Characterization Of The Factors Associated With Sccmec Mobility In Staphylococcus Aureus, Michael James Noto

Theses and Dissertations

The gene encoding resistance to β-lactam antibiotics in the staphylococci is found on the chromosome in a genomic island designated Staphylococcal Chromosome Cassette mec or SCCmec. In addition to the resistance gene, mecA, SCCmec also contains site specific recombinase genes, ccrAB, that are capable of catalyzing the chromosomal excision and integration of SCCmec. The increasing prevalence of methicillin-resistant Staphylococcus aureus infections may be due, in part, to the transfer of SCCmec into successful methicillin-sensitive S. aureus lineages. In this work we attempt to better characterize the factors associated with SCCmec transfer, beginning with CcrAB-mediated SCCmec excision in a collection of …

A Survey On The Usage Of Articaine Among General And Pediatric Dentists, Robert Louis Hollowell Iii

Theses and Dissertations

Purpose: The purpose of this study is to determine the impact that the introduction of articaine has had on local anesthetic selection by general and pediatric dentists for use in three different age groups of children.Methods: Using a cross sectional survey design, a questionnaire regarding the use of local anesthetics in children was mailed to a random sample of 500 general dentists from North Carolina, 500 general dentists from Virginia, and all 230 pediatric dentists from North Carolina and Virginia. The 16-item questionnaire included questions regarding the preferred local anesthetic to use in three different age groups, 2-3 years of …

The Effect Of A Nominal Fee On Treatment Choices For Children Needing Dental Rehabilitation, D'Audra M. Cole

Theses and Dissertations

Objective: The purpose of the study was to determine if a co-payment resulted in a differential preference for general anesthesia (GA) or oral sedation (OS) and, if so, to examine whether age, the number of appointments, perceived risks of treatment, child's awareness during treatment, or insurance type appeared to play a role in this preference.Methods: Using a cross-sectional survey design, questionnaires were distributed to caregivers of patients in the waiting room of the Virginia Commonwealth University Pediatric Dental Clinic. Two different questionnaires were distributed randomly. Both surveys described a scenario with the need for dental treatment under general anesthesia (GA) …