Medicine and Health Sciences Commons^™

Photoassisted Synthesis Of Complex Polyheterocycles Via Esipt-Driven Dearomative Intramolecular Cycloadditions, Dmitry Kuznetsov

Electronic Theses and Dissertations

This research is focused on the development of novel photoassisted synthetic methodologies that provide straightforward access to complex and diverse libraries of polyheterocycles from modularly assembled precursors. All methods are based on the dearomative cycloadditions between two components: (i) o-azaxylylenes, generated by the excited-state intramolecular proton transfer, and (ii) tethered arene groups.

We have demonstrated the synthetic utility of four new photoinduced processes that yield complex products amenable for post-photochemical modifications:

• [4+4] Cycloaddition of o-azaxylylenes to 1,3,4-oxadiazoles with subsequent dinitrogen extrusion. This reaction furnishes compounds outfitted with epoxide fragments, which undergo ring-openings with various nucleophiles; furthermore, the oxidized products …

Social Determinants Of Health Theory: Policy Entry Points For Healthcare Providers, Kiah R. Vandergrift

Electronic Theses and Dissertations

This thesis examines a shifting paradigm in the U.S. healthcare system that will re-define the role that the healthcare provider plays in the production of health. It does this by first acknowledging two differing economic theories on the production of health: Human Capital Theory and Social Determinants of Health theory, and how both schools of thought have contributed to the paradigm that healthcare providers only play a role in the end stages of health production - to heal those who are already ill. However, policy, payment, and delivery system reforms have begun to force healthcare providers to re-think how they …

Unraveling Pdi And Its Interaction With Ab Toxins, Jessica Guyette

Electronic Theses and Dissertations

Protein disulfide isomerase (PDI) is an essential endoplasmic reticulum (ER) protein that acts as both an oxidoreductase and chaperone. It exhibits substantial flexibility and undergoes cycles of unfolding and refolding in its interaction with cholera toxin (Ctx), which is a unique property of PDI. This unfolding allows PDI to disassemble the Ctx holotoxin, which is required for Ctx activity. Here, we investigated the unfolding and refolding property of PDI and how this affects its interaction with bacterial toxins. PDI showed remarkable redox-linked conformational resilience that allows it to refold after being thermally stressed. Deletion constructs of PDI showed that both …

Optimization And Characterization Of Hot-Melt Extruded Anti-Inflammatory And Local Anesthetic Bio-Adhesive Semisolid Formulation Using Design Of Experiments (Doe), Rishi Chinmay Thakkar

Electronic Theses and Dissertations

Hot melt extrusion is a versatile continuous manufacturing process extensively investigated for its applications with production of oral solid dosage forms, the aim of this study was to venture the applicability of HME in continuous manufacturing of topical semi-solid ointment formulations. Novel combination of a topical corticosteroid (Triamcinolone Acetonide) and local anesthetic (Lidocaine hydrochloride) were selected to be formulated with a water-soluble ointment base consisting of PEG 4000, PEG 1500 and Propylene glycol after performing appropriate drug-excipient compatibility studies. To determine the ratios of the solid to liquid components of the macrogol base, ‘quality by design’ approach was employed by …

Physical-Virtual Patient Simulators: Bringing Tangible Humanity To Simulated Patients, Salam Daher

Electronic Theses and Dissertations

In lieu of real patients, healthcare educators frequently use simulated patients. Simulated patients can be realized in physical form, such as mannequins and trained human actors, or virtual form, such as via computer graphics presented on two-dimensional screens or head-mounted displays. Each of these alone has its strengths and weaknesses. I introduce a new class of physical-virtual patient (PVP) simulators that combine strengths of both forms by combining the flexibility and richness of virtual patients with tangible characteristics of a human-shaped physical form that can also exhibit a range of multi-sensory cues, including visual cues (e.g., capillary refill and facial …

Development And Evaluation Of Vaccine Candidates For Senecavirus A, Bishwas Sharma

Electronic Theses and Dissertations

Senecavirus A (SVA) has been associated with several outbreaks of vesicular disease (VD) since 2014 in major swine-producing countries around the world. The virus causes VD that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Currently there are no commercial vaccines available for SVA. Here, we developed a live attenuated SVA strain by mutating a wild type SVA strain SD15-26 (wt SVA). The live attenuated virus, rSVA mSacII, replicated less efficiently in cell cultures in vitro and expressed lower amounts of VP1 and VP2 capsid proteins than wt SVA. Most importantly, the rSVA mSacII virus failed to induce clinical …

Novel Hybrid Analogs Of Estrone Origin Exhibits Cytotoxic Effects Against Egfr-Dependent Cancers, Felix Acheampong

Electronic Theses and Dissertations

Cancer is second only to cardiovascular illnesses as the deadliest human disease globally. Currently, non-small cell lung cancer (NSCLC) and triple negative breast carcinoma (TNBC) are the most frequent types of cancer and have the highest mortalities. Epidermal growth factor receptor (EGFR), a central regulator of tumor progression, is frequently overexpressed in both cancers and is a key clinical target for therapeutic intervention. Natural products and their synthetic analogs have been utilized as EGFR tyrosine kinase inhibitors (TKIs) with potent antitumor effects. However, acquired resistance limits the long-term efficacy of these drugs. Estrone has been used as a scaffold in …

Senecavirus A: Pathogenicity And Interactions With Host Cell Death Pathway, Maureen Hoch Vieira Fernandes

Electronic Theses and Dissertations

Senecavirus A (SVA) is a positive sense single-strand RNA virus of the genus Senecavirus, family Picornaviridae. Senecavirus A is an emerging picornavirus of swine, which causes vesicular disease (VD) in pigs that is clinically indistinguishable from footand- mouth disease and other high consequence VDs of swine. There is evidence that SVA has been circulating in the US swine population since the late eighty’s, however, recently the virus emerged worldwide, and it has been associated with several VD outbreaks in pigs in many of the major swine producing countries. Despite the recent surge in the number of cases of …

Design, Synthesis, And Evaluation Of Gunw-3 As A Brain Targeting Agent, Asim Najmi

Electronic Theses and Dissertations

The blood brain barrier (BBB) is a barrier in the brain that separates the peripheral blood circulation system from the central nerve system (CNS). The barrier effectively protects the brain from xenobiotics. The BBB serves as a physical barrier through the tight junction of endothelial cells that were found to be 50-100 times tighter than that of normal endothelial cells. Different drug efflux pumps such as P-glycoproteins and multidrug-resistance proteins are found to be overdistributed on the BBB. These drug efflux pumps help pump xenobiotics out if they enter the cells and serv as an additional mechanism to prevent xenobiotics …

Nutritional Transporter Mediated Drug Delivery For Cancer, Siddharth S. Kesharwani

Electronic Theses and Dissertations

Recent advancements in nanotechnology have unfolded novel opportunities in medicine, especially in targeted therapeutics and imaging for cancer. However, the majority of the existing nanotechnologies for cancer suffer from shortcomings such as (i) rapid elimination from the systemic circulation before reaching the cancer tissue. (ii) poor tumor accumulation, targeting, and penetration due to inadequate vasculature and extensive extracellular matrix in the tumor. Thus, overcoming these two limitations of nanotechnology is of considerable interests for cancer researchers. In this dissertation, we demonstrate the feasibility of glucose-modified nanoparticles (GLU-NPs) as an efficient cancer targeted-delivery system for enhancing the systemic circulation time and …

Alternative Treatment Options For Controlling Anthelmintic-Resistant Haemonchus Contortus Populations In South Dakota Sheep Herds, Adam Sarah

Electronic Theses and Dissertations

Haemonchus contortus is a common economically important gastrointestinal nematode that obliges the survival and productivity of small ruminants, especially sheep and goats. Anthelmintic resistance is a primary challenge in ruminant health management programs in preventing and controlling the H. contortus populations; therefore, there is a great necessity in finding and developing natural plant products for use as alternatives to commercial anthelmintics for controlling H. contortus in pastured sheep and goats. This dissertation has three major aims conducted in three separate studies: the first in vivo one was to evaluate the extended effect of a springtime, combined-treatment with 3 anthelmintics having …

Performance Differences Between Two Groups Of Commercial Pigs Following Experimental Infection With Prrs Virus 1-7-4, Erin Little

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is the costliest swine disease in North America. Vaccines and management alone have not been effective in controlling this disease. Genetic selection for resilience may be a complimentary approach for controlling PRRSV. The objective of this study was to estimate performance differences between two groups of pigs from the same commercial line following infection with PRRSV 1-7-4: 1) pigs sired by boars selected based on a standard index (TN-S), which emphasized feed efficiency and carcass quality; and 2) pigs sired by boars selected based on an experimental index (TN-E), which emphasized feed intake, …

Rumen Microbial Culture Library And In Vitro Analysis Of Selected Bacterial Species On Colonization Resistance Against Bovine Enteric Pathogens, Maria Antony

Electronic Theses and Dissertations

The anaerobic habitat of the four chambers in ruminant’s foregut plays a vital role in the fermentation of the food by the active involvement of the residing microbial community. The cultivability and the potential role of rumen bacteria in the field of livestock production, host health and immunity are important to study. The developed anaerobic culturing techniques enable us to culture and screen different rumen bacteria to study the anti-pathogenic effects. Whole genome sequencing and analysis help us to understand the genome level characteristics of the rumen bacterial species individually. Since the majority of the rumen biosphere is still not …

Searching For A Sense Of Place: The Process Of How Adolescent Girls Overcome Suicidality, Tamara Keefner

Electronic Theses and Dissertations

Suicide and self-harming behaviors are significant public health problems among children and adolescents globally and in the United States. Despite significant advances in recent decades to understand, prevent, and treat childhood and adolescent self-harming and suicide, suicide rates remain high. Since the National Action Alliance for Suicide Prevention set a goal to reduce suicide deaths and attempts by 40% by 2020, there has been a paradigm shift in the study of suicide yielding significant advances in the understanding of suicide and other forms of self-inflicted injury. This dissertation highlights some of the new developments in the study of suicide. First, …

The Relationship Between Campus Wellness Center Usage And Symptoms Of Depression In College Freshmen, Allison Leonard

Electronic Theses and Dissertations

There is limited research done on the relationship between the program utilization at a campus wellness facility and the symptoms of depression in college freshmen. College students have been found to have a higher prevalence of depressive symptoms than the general population, possibly due to the stressors college life can add. Studies have been done on the effects of physical activity as an intervention for depression as well as on the benefits of campus wellness facilities; however, there have been few studies that look at both campus recreation and depression. The author’s purpose for this study was to see if …

Development Of A Novel Nanotechnology-Based Vaccine Adjuvant And Delivery System For Systemic And Mucosal Immunity, Mohammed Ali Bakkari

Electronic Theses and Dissertations

Many serious infections for which there are no existing vaccines, enter by a mucosal route such as HIV, influenza, and tuberculosis, etc. Therefore, designing safe and effective mucosal vaccines that elicit robust immune response at mucosal sites is still a major challenge without a safe mucosal adjuvant. Previously, our laboratory had discovered inulin acetate as a novel toll-like-receptor-4 agonist (adjuvant). The study in this dissertation explored the application of nanoparticles prepared with inulin acetate (InAc-NPs) as a vaccine adjuvant and delivery system for enhancing mucosal immunity. The rationale behind selecting InAc-NPs is their proven ability to activate strong systemic immunity …

Using Maximum Power As A Variable For 1rm Prediction In The Squat And Bench Press, Sean O'Connor

Electronic Theses and Dissertations

Many Strength and Conditioning (S&C) coaches utilize a one-rep max (1RM) exercise test to gauge the maximal strength of athletes, and then prescribe resistance training programs based on a relative percentage of 1RM to obtain strength or power adaptations. However, many S&C coaches have raised questions regarding the safety and necessity of a 1RM test. Attempts to mitigate the weaknesses of 1RM testing have led to other methods of testing including repetition max testing (3RM, 5RM, 10RM, etc.) as well as load/velocity profiling. The main purpose of this study is to determine if 1RM can be accurately estimated from maximal …

Assessing The Impact Of Interprofessional Education On The Attitudes And Interprofessional Competencies Of Health Care Professionals: A Mixed Methods Study, Jessica L. Stadick

Electronic Theses and Dissertations

Purpose. The purpose of this study was to assess health care professional’s interprofessional collaborative competencies and attitudes towards working in teams and to examine if differences exist between professionals who have completed formal interprofessional education (IPE) and those who have not. This study was guided by the Interprofessional Learning Continuum Model.
Background. IPE is the foundation of interprofessional collaboration. Research has shown that IPE is an effective strategy to prepare health care professionals for collaborative practice; however, preventable medical errors that result from poor collaboration continues to plague the health care system. Thus, more research is needed to better …

Understanding Emotional Intelligence And Its Relationship To Clinical Reasoning In Nursing Students: A Mixed Methods Study, Heidi M. Meyer

Electronic Theses and Dissertations

Purpose. The purpose of this study was to explore emotional intelligence (EI) and its relationship to clinical reasoning in senior bachelor of science in nursing (BSN) students to gain a better understanding of how emotions are used in clinical learning experiences. This study was guided by the Four Branch Ability Model of EI.
Background. The current complex healthcare environment requires nursing students to be prepared to effectively reason in emotionally charged situations. The concept of EI and its beneficial effects in nursing are becoming more evident in the literature. However, it is still not well understood what the …

Level Of Satisfaction Among Food Pantry Clients, Staff/Volunteers, And Directors And Its Association With Client Choice In Food Pantry Layouts, Myranda Dunmire

Electronic Theses and Dissertations

Objectives: Food insecurity is an issue in rural communities, particularly among food pantry clients. Food pantries may not provide clients with the opportunity to choose their own foods (client choice), and instead may just give a set amount and type of foods. Client choice is important in regards to client health status as well as perceptions of autonomy and quality of life. Although client choice can be promoted in food pantries, it may be difficult to grasp the process of food pantry transitioning and how well changes such as these may be perceived by clients or food pantry personnel. We …

Effect Of Sulfobutyl Ether Β-Cyclodextrins On Oral And Dermal Pharmacokinetics Of Drugs, Vijay Kumar Shankar

Electronic Theses and Dissertations

Silymarin is an extract of Milk Thistle, major constituents are taxifolin, silychristin, silydianin, silybin A, silybin B, isosilybin A and isosilybin B. The in vitro, preclinical and clinical studies have demonstrated silymarin possesses hepatoprotective, anticancer, hypocholesterolemic, cardioprotective effect and dermatological beneficial effect (treatment of UV induced erythema, melanoma, non-melanoma skin cancer, rosacea, melasma, vitiligo and psoriasis) both individually and collectively. Solubility enhancement of silymarin constituent is utmost important to increase bioavailability and to improve drug developability property. The solubility of silymarin in water was enhanced by SBE-β-CD by conventional and heating method, heating method was found to be more efficient …

Pegylated Nanostructured Lipid Carries For Amphotericin B Ocular Delivery, Prit Manish Lakhani

Electronic Theses and Dissertations

The Chapter II focuses on formulation of an optimized and robust amphotericin B ocular formulation with prolonged precorneal residence and ocular tissue concentration at par or superior to the marketed preparations. Additionally, demonstrating stability of amphotericin B formulations in presence of preservative in comparison to marketed preparation, making it an ideal choice of formulation for multi-dosing. As mentioned earlier, we optimized PEGylated nanostructured lipid carriers (PEG-NLC-AmB) for ocular delivery of amphotericin B. The formulations could be autoclaved with at least one-month stability and in vivo ocular biodistribution was statistically insignificantly different compared to AmBisome®. To accomplish the aim, strategies such …

Effect Of Solvent Interaction & Soluble Microneedles On Skin Permeability To Drug Molecules, Abhijeet Maurya

Electronic Theses and Dissertations

Skin forms a formidable barrier protecting the human body from external environmental rigors and excessive loss of water; maintaining equilibrium. The barrier properties of the skin can be attributed to its unique macromolecular organization and morphology. As a route for drug administration, skin presents a large surface area and can be used for both systemic and localized targeted drug delivery applications offering several advantages over conventional drug therapy; avoidance of first pass metabolism, patient compliance, sustained or controlled delivery for an extended period, to name a few. However, the organized structure of the skin, since intended to prevent entry of …

Novel Applications Of Hot-Melt Extrusion Technology In Trans-Buccal And Topical Drug Delivery Systems, Nicole Mendonsa

Electronic Theses and Dissertations

As the buccal route of administration can avoid the first pass effect, the bioavailability of drugs that are metabolized in the liver can be increased through this route. Few studies have been conducted using oleic acid as a permeation enhancer in any trans-buccal dosage form. The objective of this study was to develop a buccal tablet using two concentrations of oleic acid for a model drug (Ondansetron) via melt extrusion technology and investigate the effects of oleic acid on the physicochemical properties of the tablet. Formulations consisting of the active drug (ondansetron hydrochloride), polymers and oleic acid were prepared by …

Testing A Modified Model Of Stress Process For Understanding Quality Of Life Among Informal Caregivers And Assessing Their Formal Service Use, Nilesh V. Gangan

Electronic Theses and Dissertations

Informal caregivers provide timely care to family members who are disabled or have a chronic condition that requires close monitoring or constant assistance. To provide adequate support to informal caregivers there is a need to assess ways to improve their quality of life (QOL) and understand how formal services can be improved. This dissertation strives to extend the knowledge available for policy makers by examining the factors that can be targeted by policy makers to improve QOL of informal caregivers as well as the factors that enable the use of formal services provided to support informal caregivers. The psychometric properties …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Animal Model Of Major Depressive Disorder, Sami Alzarea

Electronic Theses and Dissertations

Major depressive disorder (MDD) is the most prevalent psychiatric disorder, affecting about 10% of the global population and is the leading cause of disability in USA. Nearly one-third of depressed patients fail to respond to conventional antidepressant therapies. Therefore, novel therapies are needed, and require a new target and molecular mechanisms underlying MDD. Brain glial mechanisms, specifically, microglial α7 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important target for MDD associated with neuroinflammation. We hypothesized that microglial α7 nAChRs positive allosteric modulator (PAM) has an important role in the regulation of behavioral, cellular, biochemical and molecular mechanisms underlying …

Changes In Vertical Jump Components Utilizing The Myvert Device In Female Collegiate D-1 Volleyball Players, Samantha Modrick

Electronic Theses and Dissertations

The purpose of this study was to determine daily and weekly variations in vertical jump (VJ) volume and VJ height over the course of a season for female collegiate division 1 volleyball players using Vert® technology. Sixteen volleyball player’s external load was monitored through jump count, average VJ height, number of VJs completed over 20-inches, and the ratio of VJ height relative to maximum tested VJ height. The VJ parameters were compared between practices and games, and between the various position groups (outside hitters, middle blockers, libero/defensive specialist, setters). A large increase in jump count observed during pre-season, peaked at …

Evaluation Of The Effect Of Carvedilol On The Thioredoxin Pathway In H9c2 Rat Cardiomyocytes, Metab Alharbi

Electronic Theses and Dissertations

The thioredoxin (Trx) system is an endogenous antioxidant system that affects cell function and survival through controlling cellular redox status. Trx and TrxR are the main enzymes in this system while thioredoxin interacting protein (TXNIP) is a negative regulator. This study’s goal was to better understand the Trx system’s involvement in the cardiovascular disease and modulate the pathway through drug treatment. Carvedilol is a non-selective β-blocker that also exhibits antioxidant properties, but the exact mechanism of the antioxidant effect is still unclear. H9c2 rat cardiomyocytes were used to examine the effect of carvedilol on the Trx system under normal conditions. …

Development Of Tissue-Derived Biomaterial ‘Cornea-Ecmix’: Its Utility In The Management Of Corneal Diseases, Somshuvra Bhattacharya

Electronic Theses and Dissertations

Transparent cornea, at the front of the eye, mediates vision by refracting incoming light. Due to its anatomical position, cornea is susceptible to a variety of physical and chemical insults. Severe damage caused to cornea due to trauma or disease conditions can impair vision. While the cornea’s inherent repair mechanism restores partial vision loss, transplantation is the only viable treatment option if its transparency is completely lost. A global shortage of transplantable donor tissues necessitates the need for the development of functional corneal prosthetics. As cornea mostly is made up of extracellular matrix (ECM), several studies have explored the utility …

Physical Activity Environments In Rural Communities: Exploring The Relationship Between Community Perceptions And The Environment, Elizabeth M. Bye

Electronic Theses and Dissertations

Purpose: To assess the physical activity environment, community perceptions of the physical activity environment, and the relationship between these variables in rural and/or underserved communities with high obesity prevalence.
Methods: The Rural Active Living Assessment (RALA) was used to assess the programs and policies (PPA), town-wide amenities (TWA), and street segments (SSA) of the physical activity environment and the Rural Active Living Perceived Environmental Support Scale (RALPESS) was used to assess community perception of the physical activity environment within eleven rural and/or underserved communities. Each section of the RALA and RALPESS are further broken down into additional subsections in order …