Medicine and Health Sciences Commons^™

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Residential Radon Exposure, Its Contribution To Lung Cancer, And Social Determinants Of Radon Testing, Stacy Stanifer

Theses and Dissertations--Nursing

Lung cancer is a highly preventable form of cancer. Cigarette smoking is the leading cause of lung cancer followed by radon gas exposure and exposure to secondhand smoke. Kentucky leads the nation in both incidence and mortality from lung cancer. Tobacco use in Kentucky continues to be a major public health concern as nearly one-quarter of adults report current tobacco use and just over one-third of Kentucky homes with children lack rules which prohibit smoking in the home. Radon, a colorless, odorless radioactive gas, occurs naturally from the decay of uranium found in rocks and soil and is harmful when …

Associations Between Psychosocial Stressors, Genes, And Cardiovascular Disease In At-Risk Adults, Kaitlin Voigts Key

Theses and Dissertations--Nursing

Psychosocial stressors have a significant adverse impact on cardiovascular health. While better medical treatments and increased emphasis on healthy lifestyle have improved cardiovascular health for many in the United States over the past 50 years, there are persistent inequities in cardiovascular disease (CVD) rates, with the highest rates among populations burdened by chronic exposure to psychosocial stressors such as discrimination and anxiety, among others. Genetic factors may interact with these stressors further influencing the rates of CVD in these populations. The purpose of this dissertation is to examine associations among psychosocial stressors and other CVD risk factors, and the influence …

Tobacco Use And Nicotine Withdrawal Among Patients With Mental Illness, Yazan Daher Al-Mrayat

Theses and Dissertations--Nursing

People with mental illness (MI) are disproportionately affected by tobacco use compared to the general population. In fact, it is estimated that people with MI consume approximately 44% of cigarettes smoked in the United States. Moreover, the MI population is at greater risk for the negative social, economic, and health consequences associated with tobacco use and are reported to have 25-year shorter life expectancies than the general population. The impact of tobacco use is further noticeable among patients with MI who require psychiatric hospitalization. Quitting smoking in this population has been linked to fewer discharges against medical advice, better quality …

Establishing Exclusive Breastfeeding And The Influence Of Hospital Support, Martha Monroe

Theses and Dissertations--Nursing

Maternal-child health authorities recommend that infants breastfeed exclusively for the first six months of life. Currently, 25% of infants in the United States do so. Breastfeeding specific care that mothers receive from their postpartum nurses and lactation specialists is integral to successfully initiating exclusive breastfeeding. Due to the time sensitive nature of establishing milk supply, interrupting the process of lactogenesis with supplementation puts infants at high risk for early termination of breastfeeding. The purpose of this dissertation is to examine the relationship of breastfeeding care received during the postpartum hospital stay, defined as the first 48-72 hours of life, and …

Responses To Symptoms Among Patients With Heart Failure, Chin-Yen Lin

Theses and Dissertations--Nursing

Patients with heart failure (HF) suffer from chronic and progressive symptoms. Failure to respond appropriately to escalating symptoms of HF causes a delay in seeking care, which results in worse symptom status, frequent rehospitalizations, and contributes to higher mortality. In order to enhance HF self-care, promote timely care-seeking, and improve outcomes, identification of factors that affect patients’ responses to symptoms and their decisions to seek care is essential. Thus, the purposes of this dissertation were to (1) identify factors associated with patients’ responses to worsening HF symptoms, and (2) determine the impact of responses to symptoms on outcomes in patients …

It Matters Who You Live With. The Relationship Of Living Arrangement And Medication Adherence In Patients With Heart Failure, Rana Lindsay-Rahman

Theses and Dissertations--Nursing

Medication adherence is an ongoing challenge for patients with heart failure (HF) that can adversely affect mortality, morbidity, and quality of life. Living with a spouse has been associated with better adherence while living alone has been associated with poor adherence. Other factors demonstrated to affect adherence include medication complexity, perceived barriers to adherence, and depressive symptoms. Interestingly, the effect of these latter factors on adherence has not been examined in the context of the patient’s living arrangement. The purpose of this dissertation was to investigate the relationships among medication complexity, perceived barriers, and depressive symptoms with medication adherence across …

Meaningful Measurement Matters: Defining Potentially Inappropriate Medication Use To Target Cognitive Outcomes, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Preventable and unintended consequences of medication use occur in more than 25% of ambulatory and hospitalized patients, and nearly half of long-term care patients. Unfortunately, many medications used to treat common health conditions in older adults (such as anxiety, behavioral disturbances, incontinence, insomnia, depression, and pain) have also been linked to cognitive impairment and decline. Recently, substantial efforts to investigate medications and medication classes that may be associated with cognitive impairment and decline in older adults have been undertaken. Unfortunately, studies have used a wide variety of different tools to define “potentially inappropriate medication” (PIM) use, and no published literature …

Relationship Between Initial Prescription Opioid Exposure Length And Future Opioid Use Disorder Diagnosis In Opioid Naive Adolescents, Eric Lindahl

Theses and Dissertations--Pharmacy

Objectives: The long-term risks associated with the use of short-term prescription opioids in opioid naïve adolescents in not well characterized. The purpose of this study was to explore the potential association between the days’ supply of the initial prescription opioid exposure and the rates of diagnosed OUD in the subsequent 3-year period. Methods: We conducted a retrospective cohort study using a nationwide database of commercially-insured adolescents aged 12-17 at the time of the index opioid fill. A multivariable Cox Proportional Hazard regression model was developed to analyze the association of interest while accounting for known risk factors for the development …

The Impact Of Bone Marrow Transplantion On Patients With Psychiatric Diagnoses: Medication Adherence Assessment, Brittany Galop

Theses and Dissertations--Pharmacy

Objectives: We investigated whether there is a measurable difference in medication utilization for psychiatric conditions before and after bone marrow transplantation (BMT). Previous studies have identified a potential association between psychiatric conditions and immune function. We hypothesized that medication utilization for psychiatric diagnoses would be impacted by BMT.

Methods: This study was a retrospective, quasi-experimental cohort design. De-identified data was compiled from the Truven database for patients ranging from January 2009 through December 2016. Two measurements of medication utilization, proportion of days covered (PDC) and medication possession ratio (MPR) were calculated for each included Medispan-defined class of medications before analyzing …

Antiresorptive Bone Therapy Use In Advanced Lung Cancer And Associated Outcomes, Noor Naffakh

Theses and Dissertations--Pharmacy

Background/Rationale: Studies have shown antiresorptive agents decrease skeletal related events in metastatic non-small cell lung cancer. However, two prevalence studies have found low utilization rates of antiresorptive therapy in advanced lung cancer. The first study reported a rate of 14.8% during the 1995-2009 time period, while the second study reported a 33% usage rate during the time frame of 2002-2011. We believe these low utilization rates are associated with the poor prognosis of these patients. The prognosis of advanced lung cancer has improved significantly since these trials were conducted, and the utilization of denosumab has not been evaluated. We hypothesize …

Population Pharmacokinetic Modeling And Genetic Association Analysis In Infants With Neonatal Abstinence Syndrome Receiving Morphine Or Clonidine, Fei Tang

Theses and Dissertations--Pharmacy

Neonatal abstinence syndrome, or NAS, is a postnatal opioid withdrawal syndrome occurring in 55% to 94% of neonates as a result of in utero exposure to opioids. It has emerged as a significant public health issue, as its incidence more than quadrupled in the past decade. There is significant variability in disease severity and treatment outcomes in neonates with NAS due to patient-specific factors and treatment- or site-specific factors. To understand what contributes to variability in length of hospital stay and other outcomes in neonates with NAS, we assessed population pharmacokinetics (PK) of clonidine and morphine, and we investigated potential …

Extensively Drug-Resistant Pseudomonas Aeruginosa In Vitro Susceptibility And Mechanisms Of Resistance, Chanah Gallagher

Theses and Dissertations--Pharmacy

Pseudomonas aeruginosa causes severe healthcare-associated infections. Forty-eight extensively drug-resistant (XDR)-P. aeruginosa isolates were selected from 287 isolates collected for evaluation based on clinical susceptibility data. In vitro activity of commonly utilized antimicrobials (i.e. antipseudomonal beta-lactams, aminoglycosides, fluoroquinolones, and polymyxins) plus ceftolozane-tazobactam, ceftazidime-avibactam, and aztreonam-avibactam against XDR-P. aeruginosa were determined. The mechanism of resistance profile was determined through phenotypic expression analysis. Overall, polymyxin B and colistin were 100% susceptible. Apart from the polymyxins, ceftolozane-tazobactam had the highest susceptibility (94%) followed by ceftazidime-avibactam (90%) and amikacin (83%). Ceftolozane-tazobactam activity was not significantly different from ceftazidime-avibactam (p=0.6831). Only 40% of isolates …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis

Theses and Dissertations--Pharmacy

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The …

Characterization And Engineering Of Interrupted Adenylation Domains, Taylor A. Lundy

Theses and Dissertations--Pharmacy

Nature has historically served as a prolific source of biologically active molecules produced by plants, fungi, and bacteria termed natural products (NPs). These NPs often serve as therapeutic leads due to their structural diversity and unique mechanisms of action. However, many need modifications to make them more effective or safer for human use. This can be a daunting and complicated task to do via traditional organic chemistry because of their complexity, copious stereocenters, and a multitude of reactive functional groups. For this reason, enzymatic modification of these NP during their biosynthesis is an appealing option. One major class of NPs …

Opioid Use In Vulnerable Populations, Gyeon Oh

Theses and Dissertations--Epidemiology and Biostatistics

Opioid-related negative health outcomes, such as substance use disorder, misuse, and overdose deaths, have risen as long-term opioid use has increased. The benefit of using long-term opioids for pain is yet to be established. The Centers for Disease Control and Prevention provides guidelines for opioid prescribing in chronic pain, but detailed recommendations on opioid prescribing for vulnerable populations are missing due to lack of evidence-based studies. The purpose of this dissertation is to describe patterns and predictors of opioid use and assess outcomes related to prescribing opioid medications in vulnerable populations, specifically older adults with various levels of cognitive function, …

National Guard Members With Suicide Ideation: The Impact Of Stigma, Mental Health, And Trauma History On Treatment-Seeking Outcomes, Amy Brown

Theses and Dissertations--Social Work

Background. Veterans are overrepresented among suicide deaths in the United States, representing 20% of annual suicide deaths but only about 1% of the U.S. population (Department of Veteran Affairs, 2010). Of all military suicide deaths in 2016, one-third (33.4%) were in the National Guard or Reserves (Department of Defense, 2018). Previous suicidal ideation or behavior (SIB) has been shown to increase risk of subsequent ideation or behavior in both active duty and veteran samples (Bryan, Rudd, & Wertenberger, 2016; Hazlett et al., 2016) but studies of SIB specific to National Guard service members were not found.

Access and Barriers to …

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Molecular Features, Epidemiological Risk Factors, And Evidence-Based Clinical Recommendations, Ryan Decoster

Theses and Dissertations--Clinical and Translational Science

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that can form around textured-surface breast implants. In this dissertation, the cellular and molecular mechanisms of BIA-ALCL are reviewed with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Herein, the epidemiology of BIA-ALCL is systematically studied to better define the risk of BIA-ALCL and to determine the oncologic safety of smooth surface devices relative to BIA-ALCL formation. Next, a systematic review is conducted which critically appraises current clinical guidelines in order to establish an evidence base to better inform …

The Effect Of Haptoglobin Phenotypes On Markers Of Neuroinflammation In Patients With Aneurysmal Subarachnoid Hemorrhage, Kevin Hatton

Theses and Dissertations--Clinical and Translational Science

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of hemorrhagic stroke resulting from the spontaneous rupture of an intracranial aneurysm and release of oxygenated blood into the subarachnoid space. In the United States alone, aSAH occurs in approximately 30,000 patients each year and occurs, primarily, in otherwise healthy adults, frequently without warning. Sadly, approximately 40% of patients with aSAH will die in the first 30 days. Of those who survive, only about 75% will be able to live semi-independently again and only about 60% will be able to return to work.

Delayed brain injuries (DBI), which may affect up to …

Impact Of Nicu Design On Feeding-Related Outcomes In Preterm Infants, Emma Kate Calvert

Theses and Dissertations--Communication Sciences and Disorders

Many NICUs around the country are moving away from traditional open-bay designs in favor of single-family rooms (SFRs) as more is understood about the impact of the sensory environment on neurodevelopment in preterm infants. SFRs house one infant and their family for the length of the infant’s stay and are associated with improvements in numerous outcomes, including increased milk intake and weight gain and earlier transition to enteral feeding. Oral feeding remains a critical requirement for NICU discharge; however, the impact of NICU design on feeding outcomes remains unknown.

The purpose of this study was to compare feeding outcomes between …

Legibility Of Communicative Writing And Drawing In Aphasia: Does The Orthographic Medium Matter?, Nicole Waugaman

Theses and Dissertations--Communication Sciences and Disorders

Expressive language difficulties are commonplace in aphasia and are often further complicated by co-occurring motor speech disoders. Therefore, many people with aphasia (PWA) are unable to meet all their communication needs by speaking, and they may compensate with the use of communicative writing and drawing. Communicative writing and drawing can be defined as preserved, but imperfect, orthographic skills that PWA use to compensate for expressive language deficits resulting from aphasic and/or motor speech difficulties. The purpose of this study was to determine if the orthographic medium used by a PWA to write and draw influenced the legibility of their writing …

An Evaluation Of Postural Control And Balance After Anterior Cruciate Ligament Reconstruction, Kathryn Lucas

Theses and Dissertations--Rehabilitation Sciences

Over 100,000 anterior cruciate ligament reconstructions (ACLR) occur annually in the United States, with one in four individuals sustaining a second injury within the first two years after reconstruction. Due to the proprioceptive nature of the anterior cruciate ligament, the lack of regaining postural control and balance are likely large contributors to the rate of secondary injuries after ACLR. Recent literature has identified cerebral changes after anterior cruciate ligament injury and surgery, likely due to altered sensation and feedback loops. However, no study thus far has investigated the neurological feedback loops that may place this group at higher risk of …

Transcriptomic And Cellular Response To Mechanical Overload And The Underlying Role Of Macrophages In Extracellular Matrix Remodeling, Bailey D. Peck

Theses and Dissertations--Rehabilitation Sciences

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. Upon mechanical loading, including resistance exercise, which alter muscle fiber contractile activity, size, orientation and connectivity, remodeling processes must occur that involve both ECM deposition and degradation. ECM remodeling involves many cell types in muscle, but the focus of our research was directed towards macrophages, which participate in the early immune response to damage and loading. We have consistently demonstrated a significant increase in skeletal muscle macrophage abundance using pan macrophage markers (CD11b/CD68) and anti-inflammatory markers (CD206/CD163) following exercise training in …

The Effects Of Dietary Nitrate And Vitamin C On Endothelial Function And Oxidative Stress Biomarkers, Reem Basaqr

Theses and Dissertations--Pharmacology and Nutritional Sciences

Background: Endothelial dysfunction is associated with a decline in the vasodilator nitric oxide (NO) and presents alongside other cardiovascular risk factors in the early stages of atherosclerosis. Independently, inorganic nitrate and vitamin C supplementation have shown promise in providing some restoration of NO bioavailability, reduced oxidative stress, and improvements in endothelial function. Some preliminary evidence has suggested that vitamin C may augment the reduction of nitrite to further liberate NO and improve cardiovascular health. However, co-supplementation has not been adequately studied. Our objective was to compare the effect of inorganic nitrate in the form of concentrated beetroot juice (CBJ) with …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Role Of Pancreatic Amylin In Alzheimer’S And Brain Microvascular Pathologies, Han Gia Ly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer disease (AD) and cerebral vascular disease (CVD) are common causes of impaired cognition and behavior in humans. Epidemiological studies have shown that AD and CVD development and progression associated with metabolic risk factors including type 2 diabetes (T2D). However, the underlying molecular mechanisms remain elusive, which hampers the development of treatment and prevention strategies. Research results from our laboratory and others have shown that amylin, a hormone secreted by the pancreas and involved in glucose homeostasis, induces small-vessel-type pathologies and modulates amyloid composition in both familial (genetically predisposed) and sporadic forms of AD. The results indicate amylin as a …