Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock

Theses and Dissertations

The neuroendocrine hormone prolactin (PRL) and its cognate receptor (PRLr) have been implicated in the pathogenesis of breast cancer. PRL signaling relies on activating kinases such as the tyrosine kinase Jak2 and serine/threonine kinases ERK1/2, NEK3, PI3K, and AKT. In the canonical pathway of PRL signaling, JAK2 phosphorylates the transcription factor STAT5a at tyrosine residue 694 (pY694-STAT5a), preceding STAT5a nuclear translocation and transcriptional activity. However, STAT5a exists with functional duality as a transcription factor, having both pro-differentiative and pro-proliferative target genes. Other STAT family members (STATs 1, 3, and 6) have been shown to have transcriptional activity in the un-tyrosine-phosphorylated …

Knowledge, Perception, And Clinical Management Strategies Of Us Pediatric Dentists On Molar Incisor Hypomineralization, Courtney T. Brashier

Theses and Dissertations

Purpose: The purpose of this cross-sectional, survey-based study is to determine current US pediatric dentists’ knowledge, perceptions, and clinical management strategies for patients with molar incisor hypomineralization (MIH).

Methods: Following appropriate protocol and authorizations, all active pediatric dentists, general dentists, and post-doctoral student members identified by the 2020 American Academy of Pediatric Dentistry’s membership list were invited to partake in an anonymous email survey. Data regarding participants sociodemographic, education, and clinical backgrounds were collected in addition to information obtained from MIH-focused questions. Descriptive statistics and chi-square tests were used to compare and analyze data. A significance level was set at …

The Value Of Postoperative Appointments Following Full Mouth Dental Rehabilitation Under General Anesthesia, Priyanka Patel

Theses and Dissertations

Purpose: Follow-up appointments after full mouth dental rehabilitation under general anesthesia (GA) have been suggested as a method for preventing future caries and need for repeat treatment under GA. The purpose of this study is to determine current practitioner and parental perceived value of the postoperative GA appointment.

Methods: Three separate surveys were administered for this study. The pre-appointment survey asked about the guardian’s desire to have a follow-up appointment. At the follow-up appointment, the post-appointment survey ascertained the level of patient satisfaction with their follow-up appointment and postoperative experience. American Academy of Pediatric Dentistry (AAPD) members were e-mailed a …

Amixicile, A Novel Antimicrobial Agent, And Its Effect On The Salivary And Subgingival Microbiome In Rhesus Macaque Monkeys, Erin E. Block

Theses and Dissertations

Background/Purpose: Periodontitis is an inflammatory disease with a bacterial etiology in a susceptible host. A selective antibiotic with minimal systemic side effects could be a useful adjunct to traditional periodontal therapy. Amixicile is a novel antimicrobial agent that targets pyruvate: ferredoxin oxidoreductase (PFOR), an enzyme that is critical for anaerobic bacterial metabolism and has been found to have little-to-no side-effects in animal models. The aim of this study was to prospectively evaluate the effect of amixicile on clinical periodontal parameters and the composition of the oral microbiome in rhesus macaque monkeys. It was hypothesized that the amixicile would reduce growth …

A Mixed Methods Approach To Examine Racial Disparities In Adherence To Surveillance Mammography Among Breast Cancer Survivors, Megan C. Edmonds

Theses and Dissertations

PURPOSE: Annual surveillance mammography is a critical part of routine cancer care for breast cancer (BC) survivors; reducing mortality by 39%. However, disparities exist with regard to adherence to surveillance mammograms among BC survivors; Black women are 44% less likely to adhere than their White counterparts. Despite the existence of this racial disparity for over a decade, little is known about factors that explain reasons for Black BC survivors’ non-adherence. This is because most studies have not evaluated the role of healthcare delivery or psychosocial factors. Guided by the Behavioral Model for Vulnerable Populations, the purpose of this mixed methods …

Opioid System's Involvement In Ketamine's Antidepressant-Like Effects, Fan Zhang

Theses and Dissertations

Depression is one of the most debilitating disorders in the world. The currently available medications typically have a 2-4 week delay in their therapeutic effects and are ineffective for about 40% of patients. In 2000, a subanesthetic dose (0.5 mg/kg i.e.) of the dissociative anesthetic ketamine was reported to have both rapid and robust antidepressant effects in in treatment-resistant depressed patients. However, the mechanisms responsible for ketamine’s antidepressant effects remain unclear. In 2018, a clinical study reported that pretreatment with the nonselective opioid antagonist naltrexone attenuated the rapid antidepressant effect of ketamine in depressed patients. The current study investigated the …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Formulation, Characterization And Pharmacokinetic Modelling Of Excipient Enhanced Growth Spray-Dried Inhalation Powders, Serena Bonasera

Theses and Dissertations

The overall aim of this research project was to evaluate effects of spray drying parameters and storage conditions on solid-state characteristics and aerosol performance of excipient enhanced growth (EEG) powders and to formulate a stable and highly dispersible tobramycin EEG powder to be delivered to pediatric cystic fibrosis subjects using a novel positive pressure dry powder inhaler.

Micrometer-sized albuterol sulfate EEG powders were produced using a medium-sized nebulizer and optimized spray drying conditions. Using trileucine as the dispersion enhancer improved the aerosol performance but showed increased moisture absorption compared to the L-leucine formulation.

The optimized spray drying conditions were then …

Cardiac Arrest And Global Ischemia Reperfusion Injury: Role Of Mitochondria And Cannabinoid Receptor 2 Signaling., Jennifer L. Bradley

Theses and Dissertations

We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial …

Feeling The Squeeze: The Association Between Multigeneration Caregiving And Informal Caregivers’ Health, Christine L. Patterson

Theses and Dissertations

While U.S. public policy and research has focused on the health needs of the aging population, less attention has been given to the consequences informal caregivers face caring for this generation. With the segment of the population aged 65 years or older growing rapidly, it is important to understand the factors that place informal caregivers at risk for poor health outcomes and health behaviors. Since multigeneration caregivers balance more personal, work, and caregiving demands than single-generation informal caregivers of older adults, they may be at higher risk for poor health outcomes. The aim of this study was to examine the …

Perceived Efficacy Of Extrusion Of Maxillary Lateral Incisors With Aligners, Mason T. Bates

Theses and Dissertations

Purpose: To assess the perceived efficacy of aligners (Invisalign, Align Technology Inc) at performing extrusive movements of maxillary lateral incisors, determine a general threshold of when a maxillary lateral incisor is not extruding as predicted and requiring intervention, evaluate the frequency and methods of intervention to achieve the predicted extrusion, and to evaluate any related differences between orthodontists and general dentists, and between clinicians having treated various numbers of patients with Invisalign in the past 12 months.

Methods: An original 18-question survey was sent by mail to a randomized and geographically proportionate selection of orthodontic specialists (N = …

Modeling Substance Use And Mental Disorder Comorbidity Using Latent Variable And Network Approaches, Courtney T. Blondino

Theses and Dissertations

Introduction. Substance use disorder (SUD) is a common condition that affects millions of Americans. Addressing SUD has been complicated by comorbid mental disorders and co-occurring substance use. Consequently, detailing and addressing SUD and comorbid SUD represent an important goal to improve the health of Americans.

Objective. The research goal of this dissertation was to characterize the comorbidity between substance use, including tobacco use, and mental disorder symptoms measured as negative affect and externalizing symptoms in a population-based sample using latent variable and network approaches.

Methods. Waves 1 – 3 from the Population Assessment of Tobacco and Health Study were used. …

Copper Sulfide Manganese Nanoparticles For Multimodality Imaging And Therapy, Ali S. Gawi Ermi

Theses and Dissertations

Abstract

COPPER SULFIDE MANGANESE NANOPARTICLES FOR MULTIMODALITY IMAGING AND THERAPY

By Ali S. Gawi Ermi, MSc

Inorganic nanoparticles (NPs) are compatible with metal-based multi-modality molecular imaging and targeted therapy. Copper sulfide nanoparticles (CuS NPs) are attractive photoacoustic and photothermal agents and are amenable to incorporation of radionuclides and paramagnetic elements to facilitate image-guided therapy. The aim of this work is to develop manganese (Mn)- doped CuS NP, intrinsically radiolabeled with radionuclides such as (Zirconium-89 (⁸⁹Zr), Copper-64/67 (^64/67Cu) and Manganese-52/55 (^52/55Mn)). This novel approach combines Photoacoustic (PA), Positron emission tomography (PET), Single-photon emission computed tomography …

Urate Genetic Assessment In Asian And Pacific Islander Subgroups Of Pregnant Women: Implications For Personalized Medicine And Means To Reduce Health Disparities, Ali Alghubayshi

Theses and Dissertations

Gout is one of the most common rheumatic conditions and appears to have a higher prevalence in certain populations. Risk factors for gout and its precursor, hyperuricemia, are also significant risk factors for preeclampsia, major pregnancy-related morbidity. A retrospective cross-sectional study was conducted on 1059 pregnant women from different populations whom 100% reported their ethnicities from the Asian, Native Hawaiian, and Pacific Islander populations. Numerous uric acid (UA) genes and clinical conditions were addressed, and all study details were reviewed and exempted by the University of Hawaii human Studies Program (Protocol Number: 2018-00225). In this project, we hypothesized that UA …

Sleep-Related Problems, Sleep-Related Distress, And Sleep-Related Functional Status Among Adult Inpatients Receiving Palliative Care, Lisa C. Sievers

Theses and Dissertations

Palliative care patients may be at a higher risk for sleep-related problems and their negative effects compared to the general population, yet limited sleep research has been done with this population. The purpose of this dissertation was to determine prevalence rates for excessive sleepiness, insomnia, restless legs syndrome (RLS), and high risk for sleep apnea (HRSA); examine relationships between the aforementioned sleep-related problems, sleep-related distress (SD), and sleep-related functional status (SFS); and to determine which sleep-related problem measures along with age and gender predicted SD and SFS among a sample of adult palliative care inpatients. Secondary aims were to understand …

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Evaluating The Clinical Utility Of A Novel Electroencephalography System For Assessing Perioperative Neurocognition In Older Surgical Patients, Lloyd H. Barnwell Iii

Theses and Dissertations

Postoperative delirium (POD) is a public health and research priority (American Society of Anesthesiologists, 2019). POD is a risk factor for long-term neurocognitive decline, and the rate of decline is directly proportional to the severity of POD (Vasunilashorn et al., 2018). Baseline cognitive function is a strong, independent predictor for POD (Culley et al., 2017). The International Perioperative Neurotoxicity Working Group recommends baseline cognitive function be assessed for older patients prior to surgery and anesthesia (Berger, et al., 2018). Perioperative cognitive screening tools trialed in anesthesia are not routinely incorporated into clinical practice related to validity, reliability, or practicality problems …

The Role Of Insurance Coverage In Outpatient Substance Use Disorder Treatment Referral, Utilization, And Outcomes, Huyen Pham

Theses and Dissertations

Opioid-related overdoses increased dramatically in recent years. Medicaid plays a predominant role in paying for opioid use disorder (OUD) treatment. However, there is a critical gap in understanding the role of Medicaid coverage in referrals to treatment, treatment utilization, and treatment retention. The three studies used observational and quasi-experimental (i.e., natural experiment) designs leveraging state and year variation in Medicaid expansion to characterize the role of Medicaid coverage in OUD treatment. We found that individuals with OUD with Medicaid insurance were more likely to use outpatient treatment, whereas those who were uninsured were more likely to use self-help groups only. …

Cost-Effectiveness Of Interventions Targeting Hard-To-Reach Populations Living With Hiv In Eastern And Southern Africa, Deo Mujwara

Theses and Dissertations

In Eastern and Southern Africa, hard-to-reach populations (e.g., long distance truck drivers and female sex workers), defined as populations that are difficult to interact or engage with due to their unique behaviors and characteristics, are disproportionately affected by the HIV epidemic and are at high-risk of acquiring and transmitting HIV. Further, these populations have substantially low uptake of HIV testing services, and those that have been diagnosed with HIV and on antiretroviral therapy experience high loss-to-follow-up from treatment programs.

Hard-to-reach populations face unique barriers in accessing and utilizing routine HIV care such as provider stigmatization towards sex workers and highly …

A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez

Theses and Dissertations

Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. …

The Strategic Orientation Of Skilled Nursing Facilities, Jennifer R. Palazzolo

Theses and Dissertations

Since the early 2000s, skilled nursing facilities (SNFs) have operated in an environment made uncertain by changes in health care policy, growth in substitutes for nursing care, and increasing demand for services. To better understand how SNFs are strategically positioning themselves to survive and thrive, this study develops a taxonomy of strategic groups of SNFs.

A conceptual framework is based in Strategic Management Theory and classification of SNFs is based on scope of business decisions including length of stay, complexity of patients, and referral networks with hospitals. Two-step, hierarchical cluster analysis finds six strategy groups of SNFs: Post-Acute Care Focus …

Policies Addressing Barriers To Low-Income Women And Children’S Health Care Utilization In The United States And Kenya: The Role Of Physician Payments And Cash Transfer Programs, Muloongo Simuzingili

Theses and Dissertations

This dissertation examined two policies to improve low-income women and children’s healthcare utilization: physician payments and cash transfer programs. Higher physician payments increase the supply of healthcare services while cash transfers increase individuals’ demand for healthcare services. Cash transfer programs can improve health outcomes, yet the extent to which they are a cost-effective strategy is largely understudied. Therefore, this dissertation examines three overarching research questions:

1. Are Medicaid physician fees associated with access to substance abuse disorder (SUD) treatment among low-income women of reproductive age?
2. Do economic preferences moderate cash transfer program effects on children’s health care utilization? Evidence from a …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Psychological Sense Of Community Among Older Adults In Puerto Rico Two Years After Hurricane María, Thomas D. Buckley

Theses and Dissertations

Hurricane María devastated Puerto Rico in 2017 and resulted in adverse long-term outcomes. Psychological sense of community (PSOC) may serve as a protective factor against the effects of Hurricane María for older adults in Puerto Rico. Using a three-paper format, this dissertation draws on a resilience framework and theories of PSOC and the Ecological Theory of Aging to examine the role of PSOC among older adults in Puerto Rico two years after Hurricane María.

Paper one is a scoping review of the concept of PSOC in research with community dwelling older adults. I begin by presenting findings on study characteristics …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Intentions To Use Telerehabilitation For Communication And Treatment For Vision Impairments, Eric E. Hicks

Theses and Dissertations

BACKGROUND: Approximately 8.1 million people in the United States 18 and older have difficulty performing one or more daily activities because of vision impairment or blindness (Erickson, Lee, & von Schrader, 2020; Taylor, 2018). If the impairments caused by vision loss are not addressed, they can result in financial difficulties, suffering, disability, loss of productivity, and decreased quality of life (National Center for Chronic Disease Prevention and Health Promotion, 2011). Currently, in-person low vision rehabilitation services are the gold standard for teaching people how to adapt to and compensate for these deficits, however, the access and utilization of these services …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

The Effects Of Interleukin-1Β On Cardiac Reserve And Exercise Capacity In The Mouse, Habeebah Z. Vohra

Theses and Dissertations

Heart failure (HF) is characterized by dyspnea, fatigue, and exercise intolerance. Clinical evidence points to increased interleukin-1β (IL-1β) activity in patients with HF, with an IL-1 blockade improving the exercise capacity in HF patients. In healthy mice, recombinant-mouse IL-1β (rmIL-1β) induces acute systolic dysfunction, peaking 4 hours after administration. However, the direct effects of rmIL-1β on exercise capacity are unknown. We hypothesized that rmIL-1β diminishes the exercise capacity in the mouse. Adult mice were trained to run on a treadmill and exercise capacity was assessed before, 4 hours, and 96 hours after intraperitoneal administration of rmIL-1β (3 μg/kg) or vehicle …

Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia

Theses and Dissertations

Background: Adverse events and impairments associated with cancer and its treatments causes worse outcomes. Increased incidence of renal diseases among cancer patients is of particular concern. Objective: To determine the risk factors for renal disease in cancer patients and compare healthcare costs, utilization and health-related quality of life (HRQoL) of cancer patients with a renal disease and cancer patients without renal diseases. Methods: Medical Expenditure Panel Survey files from 2009 – 2018 for cancer patients was used for this study. Multiple logistic regression, generalized linear model, Poisson regression and multiple linear regression for analyses after adjusting for demographic, socioeconomic and …