Medicine and Health Sciences Commons^™

Molecular Mechanisms Of Thromboxane A2 Receptor-Mediated Invasion In Lung Cancer Cells, Xiuling Li

Theses and Dissertations--Pharmacy

Thromboxane A2 receptor (TP) has been shown to play important roles in multiple aspects of cancer development including regulation of tumor growth, survival and metastasis. Molecular mechanisms of TP mediated cancer cell invasion remain to be identified. TP agonist, I-BOP, significantly elevated several matrix metalloproteinases (MMPs) including MMP-1, MMP-3, MMP-9 and MMP-10 in A549 human lung adenocarcinoma cells overexpressing TPα (A549-TPα) or TPβ (A549-TPβ). Signaling pathways of I-BOP-induced MMP-1 expression were examined in further detail as a model system for MMPs induction. Signaling molecules involved in I-BOP-induced MMP-1 expression were identified by using specific inhibitors including small interfering (si)-RNAs of …

Localization And Functional Characterization Of Oatp4c1 Transporter In In Vitro Cell Systems And Human/Rat Tissues, Kuei-Ling Kuo

Theses and Dissertations--Pharmacy

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. In vitro studies in polarized cell lines showed that upon transfection rat Oatp4c1 localizes at the apical membrane. The objectives of this project were to further validate the subcellular localization of Oatp4c1/OATP4C1 in rat and human tissues as well …

Influence Of Oncotype Dx® On Chemotherapy Prescribing In Early Stage Breast Cancer Patients: A Claims-Based Evaluation Of Utilization In The Real World, Kenneth Neil Kennedy

Theses and Dissertations--Pharmacy

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes …

Role Of Alternative Macrophage Activation In Mediating Fibrosis In Pseudomonas Aeruginosa Pneumonia, Susan Elizabeth Birket

Theses and Dissertations--Pharmacy

Patients with cystic fibrosis who are infected with the pathogen Pseudomonas aeruginosa have shown favorable responses to the drug azithromycin (AZM). This drug works in an anti-inflammatory capacity, improving clinical outcomes and improving quality of life in this population. The drug has also been shown to affect macrophage polarization by shifting these cells away from an inflammatory phenotype toward an alternatively activated anti-inflammatory phenotype. The full impact of this phenotypic change is not well understood in the context of the response to P. aeruginosa infection, or the overall immune response in cystic fibrosis.

To understand how the AZM-polarized macrophage affects …

Nanocrystals Of Chemotherapeutic Agents For Cancer Theranostics: Development And In Vitro And In Vivo Evaluation, Christin P. Hollis

Theses and Dissertations--Pharmacy

The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate …

Role Of Cyclooxygenase-2 In Abdominal Aortic Aneurysms In Mice, Kamalika Mukherjee

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease with no available pharmacological treatment. AAA formation reduces the structural integrity of the vessel and increases the susceptibility to rupture. The inflammatory response within human aneurysmal tissue is characterized by increased expression of cyclooxygenase-2 (COX-2). Similarly, in a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, we have shown that COX-2 expression in the abdominal aortic smooth muscle layer increases early in the development of the disease. Furthermore, genetic or pharmacological inactivation of COX-2 prior to disease initiation reduces AAA incidence.

The current study utilized nonhyperlipidemic mice …

Ingestion Of Endophyte-Infected Tall Fescue Seed Induces Peripheral Vasoconstriction But Does Not Affect Cyclicity In Non-Pregnant Mares, And A Population Of Biogenic Amine Receptors Relative To Vasoconstriction Is Identified, Daniel Andrew Hestad

Theses and Dissertations--Veterinary Science

Three experiments were conducted to explore the effect of fescue toxicosis on vasoconstriction and various parameters of the estrous cycle. In the experiment of Chapter 3, a 2x2 crossover experimental design with repeated measures was implemented to test whether the ingestion of endophyte-infected tall fescue seed would alter blood hormone concentrations of prolactin, progesterone, and estradiol, interovulatory intervals, and corpus luteum blood flow. Also, Doppler ultrasonography was used to assess whether palmar artery and palmar vein lumen diameter, area, circumference, and resistivity index could be altered by the ingestion of endophyte-infected tall fescue seed. Ingestion of endophyte-infected tall fescue seed …

The Transmission Dynamics Of Equine Herpesvirus Type 1 (Ehv-1) Infection In Outbreaks Characterized Predominately By Neurologic Or Respiratory Illness, Barry Jay Meade

Theses and Dissertations--Veterinary Science

Formalized epidemiological field investigations were conducted to compare and contrast the transmission dynamics of EHV-1 neurological disease among horses stabled at Churchill Downs Racetrack, Louisville, Kentucky and of EHV-1 respiratory illness among horses stabled in the student barn at Murray State University. Differences were assessed by means of statistical and mathematical modeling techniques applied to survey and biological data collected over the course of the respective disease events.

Regression methods applied to survey data enabled the construction of a statistical model to predict a date of onset of illness for horses within each equine cohort. Comparisons of the epidemic curves …

Breeding Induced Endometritis In The Mare: The Local Innate Immune Response, Elizabeth Moran Woodward

Theses and Dissertations--Veterinary Science

Uterine inflammation after breeding is considered necessary for the clearance of excess semen and debris from the uterus. A subpopulation of mares fails to clear the inflammation in a timely fashion, and develops a persistent breeding induced endometritis (PBIE). Experiments were preformed to evaluate correlations of PBIE to endometrial quality and age. Mares of advanced age and poor endometrial quality had a higher incidence of PBIE. In addition, mares fluctuated in susceptibility to PBIE from one season to the next. The uterine inflammatory gene expression in susceptible and resistant mares within the first 24 hours after breeding was investigated. The …

Development Of Molecular Diagnostic Assays For Equine Respiratory Viruses And Analysis Of The Role Of Equine Arteritis Virus Envelope Proteins In The Early Events Of Virus Entry, Zhengchun Lu

Theses and Dissertations--Veterinary Science

There is an urgent need for detection of viral respiratory pathogens to identify the causal agent(s) involved and to prevent the spread of related diseases. The first part of this dissertation focuses on development, optimization and validation of Real-time reverse transcription polymerase chain reaction (rRT-PCR) assays for the detection of several common equine viral pathogens: equine arteritis virus (EAV), equine influenza virus and equine rhinitis viruses A and B. Emphasis of the second part of this dissertation is on studying the role of EAV envelope proteins in virus attachment and entry. Using an infectious cDNA clone of EAV and reverse …

Effects Of Methoprene On The Survivorship Of Adult Aedes Mosquitoes: A Strategy Or Inactivating Released Mosquitoes, Peter J. Brabant Iii

Theses and Dissertations--Entomology

Methoprene is a Juvenile Hormone (JH) analogue commonly used for the control of mosquito larvae. When applied to a mosquito breeding site, methoprene enters the haemolymph, where it mimics the function of JH and interferes with normal metamorphosis, resulting in larval mortality. Methoprene is commonly used for the control of larvae and has not been used as an adulticide, due to an absence of acute effects. This study evaluated possible chronic effects caused by the exposure of adult Aedes mosquitoes to methoprene. Methoprene was applied, in both technical grade and the commercially available Altosid®, topically to adults through droplet application …

Perception And Usage Of Video Streaming/Electronic Media In Nutrition Education For Kentucky Individuals, Beth Ann Oldiges

Theses and Dissertations--Nutrition and Food Systems

Nutrition Education Professionals (NEP) working for Extension Agents of Kentucky were surveyed to evaluate their use of a variety of tools in nutrition education in three areas: nutrition, food safety, and food preparation. The purpose of this research was to determine the perception and usage of video streaming/electronic media among community nutrition professionals as a means to better educate individuals in Kentucky and furthermore, to determine if demographics of NEP affect their utilization of this technology. The results concluded that regardless of demographics, NEP perceive video streaming/electronic media to be effective in nutrition education. However, age, employment length, and video …

Cross-Cultural Comparison Of Perceptions About School Feeding Programs From Ghanaian And U.S. Adults, Yolanda L. Jackson

Theses and Dissertations--Nutrition and Food Systems

Because of an increase in food insecurity over the past decade, the U.S. and many developing countries are focusing efforts on issues relating to child hunger. School feeding programs have been in existence for roughly 220 years but modifications have been made over the years to improve the quality of food they serve. Little research has been conducted about adult perceptions of school feeding programs and the impact it has on the community in the U.S. as well as developing countries such as Ghana, West Africa. Because of the gap in literature on school feeding programs and adult perceptions about …

Mild Cognitive Impairment: Statistical Models Of Transition Using Longitudinal Clinical Data, Erin L. Abner, Richard J. Kryscio, Gregory E. Cooper, David W. Fardo, Gregory A. Jicha, Marta S. Mendiondo, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Mild cognitive impairment (MCI) refers to the clinical state between normal cognition and probable Alzheimer's disease (AD), but persons diagnosed with MCI may progress to non-AD forms of dementia, remain MCI until death, or recover to normal cognition. Risk factors for these various clinical changes, which we term "transitions," may provide targets for therapeutic interventions. Therefore, it is useful to develop new approaches to assess risk factors for these transitions. Markov models have been used to investigate the transient nature of MCI represented by amnestic single-domain and mixed MCI states, where mixed MCI comprised all other MCI subtypes based on …

Equitable Consequences? Issues Of Evidence, Equity And Ethics Arising From Outdoor Smoke-Free Policies, Ann Pederson, Wendy Rice, Phoebe M. Long, Natasha Jategaonkar, Lorraine Greaves, Steven Chasey, Natalie Hemsing, Chizimuzo T.C. Okoli, Joan L. Bottorff

Nursing Faculty Publications

From Introduction:

Kass argues that an ethical approach in public health is one that places the fewest burdens on individuals’ health without significantly reducing the potential benefits of intervening. Yet many population health regulations are highly intrusive, compromising individual liberty and imposing penalties for non-compliance. Moreover, the benefits of these regulations and the burdens they impose may not be shared equally. When developing interventions, the state has, therefore, an obligation to consider the benefits and burdens, particularly on those vulnerable to health inequities and other disparities.

Assessments Of Dual Degree Programs At University Of Kentucky College Of Pharmacy, Adebayo Ogunniyi

MPA/MPP/MPFM Capstone Projects

Information about dual degree programs offered by colleges and schools of pharmacy is scarce. Factors that motivate a pharmacy student to pursue a dual degree have not been formally assessed. Furthermore, whether dual degree graduates pursue non-traditional career paths more often than single degree graduates (i.e. PharmD degree alone) is unknown. The research questions are: 1.) Why do PharmD students pursue dual degree programs at the University of Kentucky College of Pharmacy? and 2.) Does obtaining a dual degree increase the likelihood of a “non-traditional” pharmacy jobs upon graduation?

There are three main parts of this capstone project. The first …

A Systematic Review Of Physical Activity Interventions In Hispanic Adults, Melinda J. Ickes, Manoj Sharma

Kinesiology and Health Promotion Faculty Publications

Healthy People 2020 aims to achieve health equity, eliminate disparities, and improve the health of all groups. Regular physical activity (PA) improves overall health and fitness and has the capability to reduce risk for chronic diseases. Identifying barriers which relate to the Hispanic population is important when designing PA interventions. Therefore, the purpose was to review existing PA interventions targeting Hispanic adults published between 1988 and 2011. This paper was limited to interventions which included more than 35% Hispanic adults (n = 20). Most of the interventions were community based (n = 16), although clinical, family-based, and faith-based …

Predictors Of Clinician Tobacco Intervention Counseling In Six North Carolina Free Clinics, Joe G. Spangler, Eun-Young Song, Jessica Richardson Pockey, Erin L. Sutfin, Donald W. Helme, Cindy Jones, Kristie L. Foley

Communication Faculty Publications

While the poor and the uninsured are at increased risk for tobacco use, up to two thirds of these patients express interest in near-term quitting. Nonetheless, tobacco counseling rates remain low in clinics serving these patients. As part of a larger tobacco intervention project in North Carolina free clinics, we gathered baseline data on patient characteristics in six randomly selected facilities affiliated with the North Carolina Association of Free Clinics. An exit interview was completed by 231 patients; 126 (54%) were tobacco users. Among all patients, 71% had been asked by a clinician about tobacco use in the past 3 …

Recreational Music-Making In Music Pedagogy: A Manifesto For Change, Brandon Keith Wood

Theses and Dissertations--Music

The arts are an essential part of any student’s well rounded education. The future of music in education will depend on its ability to deliver relevant, effective, and measurable outcomes. However, the expectations and performance nature of traditional curricula often foster a sense of musical elitism and ostracizes students that are solely interested in music as a recreational outlet. Incorporating recreational music-making into education can provide opportunities for students to experience self-expression, creativity, social connection, and enjoyment. These values will not only enhance their education, but also lead to acquired skills for use in all areas of their lives. Activities …

Multimodal Imaging Evidence For Axonal And Myelin Deterioration In Amnestic Mild Cognitive Impairment, Brian T. Gold, Yang Jiang, David K. Powell, Charles D. Smith

Neuroscience Faculty Publications

White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using …

Elderly Onset Of Weakness In Facioscapulohumeral Muscular Dystrophy, Dominic B. Fee

Neurology Faculty Publications

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington

Pharmacology and Nutritional Sciences Faculty Publications

Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Adolescent Pregnancy, Donald E. Greydanus, Marlene B. Huff, Hatim A. Omar

Pediatrics Faculty Publications

More than 14 million adolescents in the world annually give birth, and nearly 800,000 adolescents in the United States become pregnant each year. This chapter considers concepts of teen pregnancy including risks to the mother as well as offspring, the adolescent father, issues related to abortion, and concepts of prevention of unwanted pregnancy in youth. Adolescent pregnancy is global phenomenon affecting all societies and cultures.

Menstrual Disorders In The Adolescent Female, Donald E. Greydanus, Shawn Sorrel, Hatim A. Omar

Pediatrics Faculty Publications

This chapter reviews basic concepts of menstrual disorders in adolescents beginning with an overview of menstrual physiology followed by consideration of various abnormal menstrual patterns: amenorrhea (primary and secondary), dysfunctional uterine bleeding, dysmenorrhea (primary and secondary), and premenstrual syndrome.

The Adolescent Breast, Donald E. Greydanus, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

The breast is an important organ system for the adolescent female and occasionally for the adolescent male as well. This chapter reviews basic principles of breast concerns and disorders including congenital anomalies, asymmetric breast development, under-developed breasts, virginal hypertrophy, breast masses, mastaglia, galactorrhea, gynecomastia in males, and others. Clinicians should be attuned to issues and concerns for this important structure in adolescents.

Suicide In Prepubertal Children, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Youth And Student Suicide, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Suicidal Behavior And Prevention In Adolescence, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

Suicidal behavior in youth is not uncommon and currently one of the leading causes of death in adolescence in many countries around the world. Individual risk factors for suicidality in youth include: psychiatric disorder; certain personality characteristics; genetics; gender; sexual orientation; and previous suicide attempts. Family psychopathology and environmental factors such as media contagion also contribute as risk factors. Developmental issues, including: the establishment of independence and intimate relationships; as well as the pursuit of personal and career goals; may also provide stressors leading to suicidality. Prevention and intervention strategies are considered and include: early detection and treatment of mental …

Adolescence And Contraception, Donald E. Greydanus, Carolyn M. Lentzsch-Parcells, Hatim A. Omar, Colleen B. Dodich

Pediatrics Faculty Publications

The age of adolescence is the time when most adolescents in the world become sexually active with resultant millions of pregnancies and sexually transmitted diseases. This paper considers methods of contraception for these adolescents, including oral contraceptions, transdermal contraception, mini-pills, intravaginal ring, injectable contraception, intrauterine devices, barrier contraceptives, implants, and others. It is important for clinicians caring for sexually active youth to provide information regarding contraception and appropriate contraceptive prescriptions.