Digital Commons Network^™

Evaluating The Effects Of Electronic Nicotine Delivery Systems On Smoking Reduction, Negative Mood, And Stress Among Smokers With Mental Illness, Cosima Hoetger

Theses and Dissertations

Introduction: Smokers with mental illness (MI) are disproportionately affected by negative health outcomes. Electronic nicotine delivery systems (ENDS) may represent a harm reduction tool for those who reduce and/or replace their cigarettes with ENDS. Little previous research has examined how smokers with MI respond to ENDS. This analysis aimed to address this research gap using secondary data from a randomized controlled trial of ENDS varying in nicotine delivery among smokers with and without current MI. The aims were to test 1) the effects of MI status, condition, and time on changes in smoking behavior and negative mood and stress measures, …

Impact Dynamics Of Surfactant-Laden Droplets On Non-Wettable Coatings, Amir Esmaeili

Theses and Dissertations

Owing to their excellent water repellency, non-wettable (superhydrophobic) coatings have gained tremendous attention in the past couple of decades. Alkyl ketene dimer (AKD), an inexpensive polymer frequently used in paper industry as a sizing agent, has shown potentials to become superhydrophobic. The formation of a porous structure after curing the solidified AKD for an extra-long time (4–6 days) results in superhydrophobicity, i.e., a static contact angle with water of >150° and a roll-off angle of <10°. In this work, a facile and low-cost method was used to turn the surface of AKD superhydrophobic in a very short period of time by briefly treating the coatings, obtained from isothermally heated molten AKD at 40 °C for 3 min, with ethanol. The resulting superhydrophobicity is due to the formation of porous, entangled irregular micro/nano textures that create air cushions on the surface leading to droplet state transition from Wenzel to Cassie. As a proof of concept, the same material was applied to the co-sputtered nickel-tungsten thin films, commonly used in micro/nano-electro-mechanical systems, to improve their hydrophobicity. According to the results, at least 20% increase was observed in the dynamic contact angles of the treated substrates.

In addition, this work presents a detailed high-speed imaging analysis of the influence of the molecular weight, concentration and ionic nature of surfactants on droplet …

Mobile-Based Contingency Management To Promote Daily Self-Monitoring Of Pain Severity And Related Measures In An Online Sample Of Individuals With Chronic Pain, Kathryn Polak`

Theses and Dissertations

Between 11% and 40% of the US population experience chronic pain. One promising pain management solution is remote self-monitoring. Unfortunately, low rates of adherence have impeded the use of remote self-monitoring among chronic pain patients. One robust strategy for improving adherence is contingency management (CM). This project pilot tested a fully-automated CM app (DynamiCare Rewards) programmed with an escalating variable-ratio reinforcement schedule for promoting daily self-monitoring of pain symptom severity, related variables (e.g., sleep), and prescription opioid use over a 28-day period in a sample of individuals with chronic pain. A pilot RCT compared participants randomized to CM (n …

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 …

Rheological Analysis Of The Mechanical Properties Of Murine Lungs Over The Lifespan, Olajumoke Olufunke Harrison

Theses and Dissertations

To study the effects of aging in murine lungs, we characterized C57Bl6j mice from neonatal to 24-month-old mice. Samples were divided into two groups: Young Mice (YM) and Middle Age/Old Age Mice (MOM). The YM group included the neonatal and 6-10week. The MOM group included 7- and 22–24-month-old mice. Rheological testing was performed using a TA Instruments DHR-2 Rheometer to collect the mechanics of each mice sample. Utilizing a 20-mm parallel plate fixture, a gap of 0.8-1.0-mm, and a temperature setting of 25C, we conducted a frequency sweep. Samples were the decellularized over a four-day process then lyophilized for mass …

Cryogenic Electron-Microscopy (Cryo-Em) Analysis Of Mscs, Ynai, Connexin 26 And Bioinformatic Analysis Of Cysteine And Serine In Experimental Protein Structures, Claudio Catalano

Theses and Dissertations

Functional insights into macromolecules lie in the arrangement of their molecular structures. Investigating the atomic framework of a biomolecule could unwind its biochemical mechanism, providing aid to many relevant biological questions, thus facilitating drug discovery processes. Two approaches have been used to gain knowledge at the atomic level of a protein function: experimental and computational methodologies.

From an experimental perspective, membrane proteins (MPs) were investigated. Such proteins represent ~20% of the human proteome, and ~60% of them are drug targets since they are exposed to the surface of cells and are responsible for a wide range of fundamental functions like …

Impact Of Physical Activity And Cardiorespiratory Fitness On Vascular Homeostasis In Premenopausal Women Consuming A Westernized High-Fat Meal, Lauren N. Pedersen

Theses and Dissertations

A large percentage of adults in industrialized nations consume a Westernized dietary pattern, which contributes to fasting dyslipidemia and increased risk for atherosclerotic cardiovascular disease. Evidence suggests that a single Westernized meal containing high saturated fat may induce alterations in blood lipids as well as disturb multiple factors regulating peripheral vascular homeostasis, including innate immune cell function, oxidative stress, and vascular function. Conversely, participation in acute and chronic exercise may beneficially impact an individual’s postprandial response. Therefore, this dissertation contains three manuscripts seeking to describe how acute exercise, cardiorespiratory fitness, and physical activity level impact the lipemic and vascular homeostatic …

Continuous Manufacturing Of Pharmaceuticals Using Novel Platforms, Sarah S. Aboelela

Theses and Dissertations

Pharmaceuticals have been synonymously manufactured in a centralized, batch mode with less attention to process and formulation understanding. However, due to rising drug costs, shortages, and robustness issues, in addition to the alarming lack of flexibility and agility, regulatory agencies have pushed towards switching to continuous processes. They believed in continuous manufacturing, providing cleaner, flexible, and more efficient processes. Hence, it was foreseen to reduce development and manufacturing costs, time, and environmental impact and ensured drug product quality. Over the last two decades, continuous manufacturing quality, environmental, and economic advantages have been evident through many case studies and approved products …

K-Nearest Neighbors Density-Based Clustering, Avory C. Bryant

Theses and Dissertations

Traditional density-based clustering approaches rely on a distance-based parameter to define data connectivity and density. However, an appropriate value of this parameter can be difficult to determine as it is highly dependent on the underlying distribution of the data. In particular, distribution parameters affect the scale of inter-group distances (e.g., variance); this dependence leads to a well-known inability to simultaneously detect clusters at varying levels of density. In this work, connectivity and density are defined according to the rank-order induced by the distance metric (i.e., invariant to the expected scale of the distances). Connectivity by k-nearest neighbors and density by …

Continuous Preparation And Application Of Novel Heterogeneous Catalysis, Michael B. Burkholder

Theses and Dissertations

Transition metal heterogeneous catalysts are widely used across many chemical industries to reduce waste and emissions and reduce production time while increasing rate. The prevalence of these materials results from the complex relationship between metal nanoparticles and supports affecting final catalytic performance. Rational catalyst synthesis describes the ability to precisely engineer structures through controlled preparation. Novel materials and continuous processing represent a promising approach for rational catalyst synthesis.

The application of these catalysts in continuous, multiphase processes, such as cross-coupling reactions, oxidation chemistry, and nitroreduction processes, are paramount to developing new commercial routes for high-value products. Pd/G catalysts synthesized by …

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 …

Characterization Of Cytochrome P450 3a4 Structure And Ligand Binding Mechanism In Anionic Nanodiscs, David T. Sweeney

Theses and Dissertations

The Cytochromes P450 superfamily are ubiquitous throughout life and are present in some viruses. Humans encode for 57 of these enzymes that are involved in the metabolism of ~90% of all chemicals. These membrane-bound monooxygenase enzymes utilize a heme protoporphyrin at their active site to activate molecular oxygen and oxidize their substrates through an intermediate deemed nature's most powerful oxidizer. They are a powerful system at our disposal yet understanding of their structure and ligand binding mechanisms in the presence of a lipid bilayer remains poorly understood. The focus of this work is on Cytochrome P450 3A4 (CYP3A4). We set …

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. …

Prognostic Modeling Of Recovery Following Stem Cell Transplantation, Brielle A. Forsthoffer

Theses and Dissertations

Predicting the trajectory of lymphoid recovery following myeloablative hematopoietic stem cell transplantation (SCT) can help guide subsequent therapeutic decisions, since poor recovery has been associated with graft-versus-host disease (GVHD), relapse and mortality. Previous attempts at classifying patients depended on absolute criteria being set prior to modeling absolute lymphocyte counts (ALCs) over time. Having an empirical clinical decision support tool for objectively determining the trajectory an individual might take during their recovery would be advantageous. We propose using growth-based trajectory modeling (GBTM) and growth mixture modeling (GMM), which utilize machine learning algorithms to empirically identify latent groupings of data. Due to …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

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 …

Therapeutic Modalities For Preventing Osteoarthritis Following Trauma To The Knee, Kayla M. Scott

Theses and Dissertations

Over 32.5 million adults in the United States and 300 million worldwide have osteoarthritis (OA). To date, there are no disease-modifying therapeutics, only strategies to slow OA progression through pain management, regenerative medicine approaches, and ultimately joint replacement.

On a microscale, a phenotypic shift of the normally quiescent articular chondrocytes leads to aberrant expression of pro-inflammatory and catabolic pathways, which are hypothesized to contribute to OA progression. Of note, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and WNT/β-catenin signaling are key players disrupting cartilage homeostasis and driving inflammatory pathway activation. These pathways become dysregulated and form a positive feedback loop, increasing …

In Vitro Evaluation Of High Flow Gas And Aerosol Drug Delivery Using Anatomically Biorelevant Infant And Child Airway Replicas, John Wilkins Jr

Theses and Dissertations

Respiratory care has greatly evolved from the use of an iron lung to treat patients with polio to now having at home continuous positive airway pressure (CPAP) machines for sleep apnea. Additionally, advances have been made in drug delivery as common delivery methods, such as spray and nebulizer devices, are used extensively for treatment of various pulmonary diseases and in some cases even used to deliver vaccines. More recently, 3D printing has allowed for anatomically-accurate physical airway models to be developed to better understand the countless number of therapies involving regional aerosol deposition as well as physical effects of therapies …

Ligand Effects On Electronic, Magnetic, And Catalytic Properties Of Clusters And Cluster Assemblies, Dinesh Bista 9288522

Theses and Dissertations

Ligands commonly protect metallic clusters against reacting with outside reactants. However, ligands can also be used to control the redox properties enabling the formation of super donors/acceptors that can donate/accept multiple electrons. This thesis focuses on how the ligands can be used to control the electronic and magnetic features of clusters and ligand stabilized cluster-based assemblies, leading to nano pn junctions with directed transport, the possibility of light-harvesting, and catalysts for cross-coupling reactions. The thesis addresses three distinct classes of clusters and their applications. The first class of cluster “metal chalcogen clusters” is the central idea of the thesis focused …

Prediction Of Mrna Abundance In Firmicutes: Steps Towards A Universal Model Of Prokaryotic Gene Expression, Jesse J. Raynor

Theses and Dissertations

Measurements of gene expression find use in many areas related to the characterization of prokaryotes. For example, metabolic modeling is commonly employed to assist in the design of engineered microbes by helping to elucidate the organism’s extant metabolic processes. With insights generated from the modeling procedure, targeted genetic modifications can be introduced to the organism to bring about some desired effect. Metabolic models based upon the “flux balance analysis” method (or FBA) can be made more accurate by integrating gene expression data, such as that from RNAseq experiments. For various reasons, gene expression data is not always available for every …

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. …

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 …

Development Of Unnatural Amino Acid Mutagenesis Technologies To Control Enzyme Activity And Synthesis Of Chemically Reactive Ubiquitin Probes, Jenny Cheung

Theses and Dissertations

Most of the work vital for the survival of the cell are performed by proteins. The primary sequence of proteins is composed of 20 canonical amino acids. However, these 20 amino acids do not offer the full range of functionalities needed for proteins to do their job. Often times, post-translational modifications (PTM’s) occur to add the required functional group. This interaction between all the different proteins in the proteome in addition to PTM’s create a complex system that scientists are still trying to unravel to this day. Many different tools had been developed for this purpose, and one such tool …

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 …

Patient Blood Management Programs And Their Association With Patient And Organizational Outcomes, Sandra L. Lamm

Theses and Dissertations

Blood transfusions are the most common hospital procedure. However, many transfusions may be unnecessary. These unnecessary transfusion may expose patients to the potential risks of transfusion without improving patient outcomes Patient blood management (PBM) programs emphasize conserving a patient’s own blood resources and only transfusing the minimum amount needed. This study examined the organizational and environmental factors associated with a hospital having a PBM program, or having processes based on PBM, and their impact on organizational and patient outcomes potentially affected by blood transfusions.

A PBM survey was created for this study and used to gather information on hospitals having …

Examining The Impact Of Entrepreneurship Training On Entrepreneurial Mindset And Economic Well-Being, Sombo Muzata

Theses and Dissertations

This study used a mixed methods research design to examine the impact of entrepreneurship training on entrepreneurial mindset and economic well-being using the RVA Works Entrepreneurship Training Program as a case study. With human capital theory as a theoretical framework, a combination of 55 interviews and 36 surveys were used to answer the research questions. The study found that entrepreneurship training positively impacts an entrepreneurial mindset. The impact of the training on entrepreneurial mindset differed by participants age and educational level. Study participants applied their entrepreneurial mindset to their businesses, jobs, and other aspects of life. Participation in the program’s …

Physiological And Subjective Effects Of Protonated Nicotine Liquids In Tobacco Users, Alisha Eversole

Theses and Dissertations

Electronic cigarettes (ECIGs) produce an aerosol by heating a liquid that often contains nicotine. The nicotine can be protonated, potentially making the aerosol easier to inhale than freebase nicotine. This study’s purpose was to determine, in inhaled tobacco product users, the effects of three concentrations of protonated nicotine aerosolized at two different power settings (in watts).

Twenty-two participants completed six sessions that varied by liquid nicotine concentration (10, 15, or 30 mg/ml protonated nicotine) and device power (15 or 30 W). Participants took 10 puffs from each product and then used each product for 60 minutes ad libitum. Plasma …

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 …