Medicine and Health Sciences Commons^™

A Molecular Dynamics Investigation Of Lipid Bilayer Perturbation By Pip2, Dmitry Lupyan, Mihaly Mezei, Diomedes E. Logothetis, Roman Osman

Physiology and Biophysics Publications and Presentations

Abstract

Phosphoinositides like phosphatidylinositol 4,5-bisphosphate (PIP₂) are negatively charged lipids that play a pivotal role in membrane trafficking, signal transduction, and protein anchoring. We have designed a force field for the PIP₂ headgroup using quantum mechanical methods and characterized its properties inside a lipid bilayer using molecular dynamics simulations. Macroscopic properties such as area/headgroup, density profiles, and lipid order parameters calculated from these simulations agree well with the experimental values. However, microscopically, the PIP₂ introduces a local perturbation of the lipid bilayer. The average PIP₂ headgroup orientation of 45° relative to the bilayer …

Long-Term Fish Oil Supplementation Induces Cardiac Electrical Remodeling By Changing Channel Protein Expression In The Rabbit Model, Xulin Xu, Min Jiang, Yuhong Wang, Timothy Smith, Clive M. Baumgarten, Mark A. Wood, Gea-Ny Tseng

Physiology and Biophysics Publications and Presentations

Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s)/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography - mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of …

Nursing Home Organizational Characteristics And Utilization Of Cancer-Related Medical Services, Chun-Chieh Lin

Theses and Dissertations

Cancer is the second leading cause of death in the U.S and is more common among the elderly. Since frailty and other age related conditions put the elderly at risk for nursing home care, nursing homes may be the site of care and death for many elderly cancer patients. However, there is a large gap in knowledge concerning cancer treatment of elderly nursing home residents. Since residents rely heavily on their nursing facilities, nursing homes might influence them in their treatment decisions. After controlling for resident and nursing home market characteristics, this study applies Andersen’s Behavioral Model to examine whether …

The Effects Of Pet Ownership On Physical Well-Being In Older Adults, Tami Pohnert

Theses and Dissertations

A large percentage of Americans own pets which may impact their health. This study examines pet ownership’s effect on well being in older adults looking at race/ethnicity. A sample of 6,565 older adults (>60) was selected from the Third National Health and Nutrition Survey. Pet owners comprised 28.3% of the sample. The theories of symbolic interaction and social integration were used to examine pet ownership’s effect on physical components of well-being. The descriptive results showed statistically significant differences in age, education, income, and marital status between pet owners and non-pet owners. Pet owners were younger, more educate, higher income …

Role Of Oxidative Reactive Species And Antioxidants In Metabolism And Transport Of Therapeutic Drugs, Svetlana Verenich

Theses and Dissertations

Oxidative stress (OS) is a frequent complication of various disease conditions such as Alzheimer’s and Parkinson’s disease, atherosclerosis, preeclampsia, rheumatoid arthritis, diabetes including gestational diabetes, etc. OS is defined as an imbalance between the production of reactive species and the ability of an organism to detoxify the reactive intermediates and repair the damage. As a result of OS, the excess of reactive species such as oxygen superoxide (O2-), hydroxyl radical (OH), peroxynitrite (ONOO−), 4-hydroxynonenal (4HNE), etc., have a tendency to react with nearby proteins/nucleic acids/lipids changing their functionality or inactivating them completely. The organism has many ways to protect itself …

Autotaxin: A Regulator Of Oligodendrocyte Differentiation, Larra Yuelling

Theses and Dissertations

In order for oligodendrocyte progenitor cells (OPCs) to differentiate into fully mature, myelinating oligodendrocytes, they must be specified at the correct times and undergo coordinated changes in both gene expression and morphology. As oligodendrocytes differentiate, they transition from a bipolar morphology into a morphology characterized by a complex network of multiple processes, which will eventually generate membranous structures necessary for myelination of axonal segments. As changes are observed in cellular morphology, oligodendrocytes also undergo changes in their gene expression profile and express genes necessary for both early and later stages of development such as olig1 and myelin basic protein (mbp), …

Virginia Dental Journal (Vol. 87, No. 1, 2010)

Virginia Dental Journal

No abstract provided.

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic (Pk) Properties Based On Quantitative Structure Pharmacokinetic Relationships (Qspkr) And Interspecies Pharmacokinetic Allometric Scaling (Pk-As), Prajakta Badri

Theses and Dissertations

This research developed validated QSPKR and PK-AS models for predicting human systemic PK properties of three, preselected, pharmacological classes of drugs, namely opioids, β-adrenergic receptor ligands (β-ARL) and β-lactam antibiotics (β-LAs) using pertinent human and animal systemic PK properties (fu,, CLtot, Vdss, fe) and their biologically relevant unbound counterparts from the published literature, followed by an assessment of the effect of different molecular descriptors on these PK properties and on the PK-AS slopes for CLtot and Vdss from two species (rat and dog). Lipophilicity (log (D)7.4) and molecular weight (MW) were found to be the most statistically significant and biologically …

In-Vitro Metabolism And Protein Binding Of 5-Hmf, A Potential Antisickling Agent, Taghrid Obied

Theses and Dissertations

Purpose. 5-HMF is a potential antisickling agent forming a Schiff-adduct with hemoglobin (Hb). In-vitro studies were designed to identify the metabolic pathways of 5-HMF in human hepatic cytosol, to assess inter-species differences in its hepatic metabolism, and to predict in-vivo PK properties. Moreover, metabolism of 5-HMF in human RBCs was investigated. Finally, in-vitro studies were done to characterize 5-HMF binding kinetics with human Hb and albumin (HSA). Methods. NAD+ reduction was monitored at 340 nm in human hepatic cytosol for 5-HMF (26 mM) and prototypical ADH and ALDH substrates in the presence or absence of their inhibitors. Furthermore, concentration-dependency studies …

The Role Of Methyl Cpg Binding Domain Protein 2 (Mbd2) In The Regulation Of Embryonic And Fetal Β-Type Globin Genes, Merlin Nithya Gnanapragasam

Theses and Dissertations

The reexpression of the fetal γ-globin gene in adult erythrocytes is of therapeutic interest due to its ameliorating effects in β-hemoglobinopathies. We recently showed that Methyl CpG Binding Domain Protein2 (MBD2) contributes to the silencing of the chicken embryonic ρ-globin and human fetal γ-globin genes. We further biochemically characterized an erythroid MeCP1 complex that is recruited by MBD2 to mediate the silencing of these genes. These observations suggest that the disruption of the MeCP1 complex could augment the expression of the fetal/embryonic globin genes. In the studies presented in chapter 2, we have pursued a structural and biophysical analysis of …

The Impact Of A Coordinated Care Program On Uninsured, Chronically Ill Patients, Jennifer Neimeyer

Theses and Dissertations

This study explored how being enrolled in a program that both coordinates patient care and provides a medical home changes health care utilization for uninsured patients, more specifically those persons with chronic conditions, through the use of the Chronic Care Model and Andersen and Aday’s Behavioral Model for Access to Health Care. Uninsured patients typically seek out care in a fragmented manner, which may lead to ineffective and inefficient care, especially for conditions that may require ongoing treatment and monitoring such as chronic conditions. The methodology used to examine the relationship between the interaction of enrollment and chronic condition status …

The Impact Of Medicaid Disproportionate Share Hospital Payment On The Provision Of Hospital Uncompensated Care And Quality Of Care, Hui-Min Hsieh

Theses and Dissertations

Medicaid Disproportionate Share Hospital (DSH) payment is one of the major funds supporting health care providers as they treat low-income patients. However, Medicaid DSH payments have been targeted for major budget cuts in many health policy reforms. This study examines the association between the changes in Medicaid DSH payments resulting from the BBA policy changes and hospital outcomes, in terms of hospital provision of uncompensated care and quality of care. Economic theory of non-profit hospital behavior is used as a conceptual framework, and longitudinal data for California short-term, non-federal general acute care hospitals for 1996-2003 are examined. California was especially …

The Role Of The Methyl Dna Binding Domain Protein 2 (Mbd2) In Breast Cancer, Omar Mian

Theses and Dissertations

Methyl-CpG Binding Proteins (MCBPs) are thought to function as the interpreters of epigenetic information encoded in cytosine methylation. Their ability to translate DNA methylation into local transcriptional repression has sparked interest in the role of Methyl-Binding Domain Proteins (MBDs) in cancer, where repatterning of CpG methylation is common. In this dissertation I summarize and discuss observations made in the Ginder Lab linking MCBPs to the progression of neoplastic disease. It is clear from our work that the Methyl Binding Domain Protein 2 (MBD2) is necessary for the persistent repression of critical tumor suppressor genes in breast cancer. We show that …

Dendritic Spine Density Varies Between Unisensory And Multisensory Cortical Regions, Moazzum Bajwa

Theses and Dissertations

In the brain, the dendritic spine is a point of information exchange that extends the neuronal surface on which synapses occur, as well as facilitates and stabilizes those contacts. Furthermore, dendritic spines dynamically change in shape and number in response to a variety of factors. Dendritic spine numbers are reduced in mental retardation, enhanced during development, sensory enrichment or physical exercise, or fluctuate during the reproductive cycle. Thus, for a given neuron type, it might be expected that dendritic spine number might achieve a dynamic optimum. Indeed, many studies of spine density of pyramidal neurons in sensory cortex indicate that …

Alternative Regulation Of The Alginate Algd Operon By An Activated Algb In Nonmucoid Pseudomonas Aeruginosa Is Dependent On Sigma 54, Jean Kim

Theses and Dissertations

Alginate overproduction by Pseudomonas aeruginosa, which causes a mucoid phenotype, is a major virulence factor associated with chronic pulmonary infections in cystic fibrosis patients. Expression of the algD operon for alginate biosynthesis requires three major regulators in association with the ECF sigma factor, σ22, in mucoid strains that are typically defective in anti-sigma factor, MucA. One such algD regulator is AlgB, a member of the NtrC family of two-component systems, which typically utilize σ54. However, neither σ54 nor the cognate sensor kinase (KinB) of AlgB are required for algD expression in such mucoid strains. I hypothesized that KinB-phosphorylated AlgB must …

Novel Cinnamic Acid-Based Dehydropolymers For Emphysema: In Vitro And In Vivo Assessment Of Their Activities, Bhawana Saluja

Theses and Dissertations

Pulmonary emphysema is a serious worldwide illness, causing progressive and irreversible alveolar wall loss and difficulty in breathing. It is caused mostly by cigarette smoking. However, its unresolved complex and multiple pathogenic mechanisms have left this disease without effective pharmacotherapy. This project hypothesized that cinnamic acid-based dehydropolymers (DHPs), originally discovered as novel anti-coagulants, protect against emphysema through their potent triple inhibitory actions against oxidative stress, inflammation and elastase, some of the pathogenic mechanisms associated with this disease. Three in vitro inhibitory activity assays for oxidative stress, lung inflammation and neutrophil elastase (NE) were developed and used to identify the most …

The Role Of Synaptically Evoked Plateau Potentials In Retinogeniculate Development, Emily Dilger

Theses and Dissertations

We study the activity-dependent refinement of sensory systems by using the mouse retinogeniculate system as a model. Spontaneous retinal waves lead to robust excitatory post-synaptic activity in developing relay cells in the dorsal lateral geniculate nucleus (dLGN) of the thalamus and are reportedly needed to help guide the segregation of retinal inputs into eye-specific domains as well as for the pruning of extraneous retinal inputs onto single dLGN relay cells. The composition of retinally evoked post-synaptic activity activated by these retinal waves in dLGN is largely unknown, but based on our in vitro recordings, such activity seems well suited to …

Patient Ventilator Dyssynchrony: Types, Frequency And Patterns In Critically Ill Adults, Karen Mellott

Theses and Dissertations

Patient ventilator dyssynchrony (PVD) occurs frequently, but little is known about the types, frequency and patterns of PVD for longer than 30 minutes. Deeper levels of sedation are associated with PVD. Evaluation of ventilator graphics and the ability to identify PVD should assist clinicians to optimize patient ventilator interactions and promote earlier interventions. The purpose of this study was to identify the different types, frequency and patterns of PVD in critically ill adults and determine the effect of sedation level on PVD. Thirty medical and surgical ICU adult patients were enrolled; 27 were used for analysis. Pressure/time and flow/ time …

The Prognostic Potential Of The Epidermal Growth Factor Receptor And Nuclear Factor Kappa B Pathways And Associated Therapeutic Strategies In Patients With Squamous Cell Carcinoma Of The Head And Neck, Pamela Wirth

Theses and Dissertations

Little is known about the signaling pathways that contribute to treatment response in advanced stage head and neck tumors. Increased expression of epidermal growth factor receptor (EGFR) and downstream pathways such as nuclear factor kappa B (NFκB) are implicated in aggressive tumor phenotypes and limited response to therapy. This study explored the rationale for combining the proteasome inhibitor bortezomib with the EGFR inhibitor gefitinib in a subset of head and neck squamous cell carcinomas with high EGFR gene amplification. Drug responses of gefitinib and bortezomib as single agents and in combination within head and neck squamous cell carcinoma cell lines …

Antibiotic Use By Members Of The American Association Of Endodontics: A National Survey For 2009- A Follow Up From The Report In 1999, Pye Kyu

Theses and Dissertations

The purpose of this study was to determine the changes in prescribing habits of active members of American Association of Endodontics (AAE) with regards to antibiotics in comparison to the findings reported by Yingling et al. in 1999. The invitations to take the online survey were sent via email to 2593 active members. A response rate of 37.75% was obtained. It was determined to be adequate for analysis and for comparison to the results obtained by Yingling et al. Comparisons between the percentages shown in this survey and the previous survey were tested using a z-test. An ANOVA model was …

The Association Between Lead Exposure And Respiratory Health In Children, Colleen Coleman

Theses and Dissertations

Purpose: The substantial impact of indoor air quality and environmental hazards in the home on one’s health has long been recognized in the field of public health. This cross-sectional study investigates the risk between home based hazards, specifically lead, and respiratory health in children. The objective of this study is to examine the extent to which children testing positive for blood lead exposure are at an increased risk for having poor respiratory health. Methods: A nationally representative sample of 977 children ages 1- 6 years was obtained from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Information from the …

Examining The Association Of Fruit And Vegetable Intake And Breast And Prostate Cancer Screening, Mark Yu

Theses and Dissertations

Breast and prostate cancer incidence and mortality have been steadily decreasing. Reasons for these reductions may be related to increased rates of cancer screening and other factors such as improvements in diet, including consumption of fruits and vegetables. We wanted to determine if individuals who get screened for breast and prostate cancer are more or less likely to consume adequate servings of fruit and vegetables. A cross-sectional study using the BRFSS survey was conducted. Individuals included in this study (n=26,222), were asked about their breast or prostate cancer screening history. They were also asked about their servings per day of …

Cardiovascular Reactivity To Forgiveness In Females, Carolyn Mccrocklin

Theses and Dissertations

Empirical evidence exists directly relating forgiveness to physiological markers of cardiovascular health based on the manner in which individuals respond to interpersonal offenses. Extant literature has identified the harmful effects of stress in cardiovascular disease and health in general and unforgiveness has been identified as a stressor with potential implications for cardiac health. Understanding cardiac response to the stress of unforgiveness may have favorable implications for heart disease prevention and treatment in women and may prove to be beneficial in reducing allostatic load.

Community Voice: Taking It To The People, Guidelines For Conducting A Process Evaluation, Tiffany Mcghee

Theses and Dissertations

Background The Community Voice program is designed for African-Americans and explores key factors that can contribute to African-American infant mortality. This program was implemented in Henrico County based on Virginia Health Statistics that the White infant mortality rate average during the years of 2001-2005 was 5.3 deaths per 1,000 live births and in the same time period the infant mortality rate for African-Americans was 13.7 deaths per 1,000 live births. At the time of implementation of the program, no plans to evaluate the program had been made. Objective This evaluation was designed to develop guidelines regarding the evaluation process of …

Vitamin B6 Metabolism And Regulation Of Pyridoxal Kinase, Amit Gandhi

Theses and Dissertations

Pyridoxal 5'-phosphate (PLP) is the cofactor for over 140 vitamin B6 (PLP)-dependent enzymes that are involved in various metabolic and biosynthetic pathways. Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two key enzymes that metabolize nutritional forms of vitamin B6, including pyridoxal (PL), pyridoxine (PN), and pyridoxamine (PM) to the active cofactor form, PLP. Disruption of the PLP metabolic pathway due to mutations in PNP oxidase or PL kinase result in PLP deficiency, which is implicated in several neurological pathologies. Several ingested compounds are also known to result in PLP deficiency with concomitant neurotoxic effects. How …

The 2009 H1n1 Influenza A “Swine Flu” Virus Presentation In Virginia 2009, Tammie Smith

Theses and Dissertations

Objective: 2009 H1N1 influenza was first detected in the Northern Hemisphere in April 2009. National data have suggested that the novel influenza virus disproportionately causes severe illness in children and young adults, a somewhat different presentation from traditional seasonal flu which normally strikes hardest in the very young and older adults. This may or may not be the case in Virginia, which, if it is different, may suggest a need to alter flu prevention messages and vaccine policy as the outbreak continues through the fall 2009-10 influenza season. This report examined the early presentation of the new influenza virus in …

Client Perceptions And Working Alliance: Predictors Of Outcome?, Theresa Do

Theses and Dissertations

BACKGROUND In recent years, there has been a push to measure and monitor the quality of health care and the delivery of effective services. Substance use disorders are debilitating and in order to better understand this facet of substance abuse, it is important for organizations and providers to assess the quality of services, client satisfaction, and the relationships that exist between clients and treatment providers. PURPOSE The purpose of the study was to (1) assess the extent of the relationship between measures of client perceptions of satisfaction and treatment outcomes and (2) to assess the relationship between measures of therapeutic …

Association Between Preconception Multivitamin Use And The Risk Of Preeclampsia/High Blood Pressure In Pregnant Women, Krisandra Allen

Theses and Dissertations

Gestational Hypertension and Preeclampsia are significant causes of morbidity and mortality among pregnant women and neonates. This study examined the relationship between multivitamin use and incidence of reported high blood pressure or preeclampsia using data from the 2007 Oregon State Pregnancy Risk Assessment Monitoring System (PRAMS). Overall there were n=1894 women included in the study. Women were asked two to four months after delivery to report their multivitamin or prenatal vitamin usage in the month prior to conception and were categorized as daily users, or less than daily users. The unadjusted prevalence of high blood pressure or preeclampsia was 13.4% …

Developing A Comprehensive Youth Obesity Initiative For The State Of Virginia, Jennifer Thompson

Theses and Dissertations

The 2009 Virginia General Assembly Session unanimously voted to change the legislation governing the Virginia Tobacco Settlement Foundation to create the Virginia Foundation for Healthy Youth (VFHY) and incorporate childhood overweight and obesity prevention and reduction in its mission. In order to successfully meet the requirements of this legislation, VFHY needed assistance developing a strategic plan for the obesity initiative and a knowledge base to draw from. A comprehensive assessment of the status of Virginia’s childhood obesity problem was conducted, including the prevalence of the illness, the barriers existing to and the benefits to obesity prevention programs, the need for …

Use Of Oral Chemotherapeutic Medications In Non-Traditional Ambulatory Settings, Sameer Arora

Theses and Dissertations

Background: Cancer is the second leading cause of death in economically developed countries. The use and availability of oral treatment for cancer has increased dramatically in the past 10 years. Few studies have described the use of oral chemotherapy in non-traditional ambulatory settings by health care professionals across different specialties. Objective: The purpose of this study is to describe the usage of oral chemotherapeutic medications in ambulatory settings. Methods: Cross sectional study of 2007 NAMCS Survey analysis involving 21,761 subjects aged 18 years and above with cancer who participated in the 2007 National Ambulatory Medical Survey (NAMCS). Main Outcome Measure: …