Medicine and Health Sciences Commons^™

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

The Use Of Electroacupuncture For Cervical Ripening In Pregnant Women, Becky A. Nauta

Theses & Dissertations

The purpose of this study was to compare cervical ripening outcomes, based on Bishop scoring methodology, of pregnant women receiving usual care treatment (UC) with those receiving electroacupuncture plus UC. A sample of 36 pregnant women completing their 39^th week of gestation was randomized into one of the two groups. The women in the UC group continued to meet with their provider on a weekly basis until delivery. The women in the electroacupuncture plus usual care group met with their provider on a weekly basis and also received electroacupuncture treatments: three in the 39th gestational week and two in …

Adoption Of Medication Management Technologies By U.S. Acute Care Hospitals After The Hitech Act, Aastha Chandak

Theses & Dissertations

Medication errors and adverse drug events (ADEs) are a significant public health concern in the United States as they pose a threat to patient safety. The medication management process is a complicated process in U.S. acute care hospitals, consisting of a series of steps such as ordering, transcribing, dispensing and administration and each step is prone to medication errors.The use of technology is considered to be an important intervention in improving the medication management process and thereby reducing medication errors and ADEs and further improve patient safety. The Health Information Technology for Economic and Clinical Health (HITECH) Act, implemented in …

Chemosensitization Effect Of Sp1017 On Multiple Myeloma, Hangting Hu

Theses & Dissertations

Multiple myeloma (MM) is a hematological malignancy of plasma cells that are predominantly located in bone marrow (BM). Despite recent improvements in MM treatment by introduction of several novel agents includingimmunomodulatory drugs, proteasome inhibitors and the use of the drug combinations, MM remains incurable and almost all patients eventually relapse or become refractory to the current treatment regimens. So the current challenge of MM treatments is to maintain treatment response, prevent relapse and eventually prolong survival.

Here we demonstrated that Pluronic block copolymers ((Pluronic L61: Pluronic F127 = 1:8 w/w, SP1017) significantly increase cytotoxicity of proteasome inhibitors (Bortezomib, BTZ or …

Bone Loss Quantification Following Extraction In Rats: A Foundation For Grafting And Regenerative Studies, Emily Willett

Theses & Dissertations

Background: Loss of the alveolar ridge width and height following extraction is well-documented and several techniques, including grafting, have been proposed to reduce bone loss. Purpose: To characterize the pattern of bone turnover and inflammation after extraction and to initiate a study of the effect of grafting and local administration of simvastatin (SIM). Methods: Thirty-two retired-breeder rats underwent extraction of the right maxillary first molar and standard surgical defect creation under inhalation anesthesia. The left side of each animal served as the unmanipulated control. Comparison of groups (n=8, ANOVA) was done at days 0, 7, 14, and …

Effects Of Flash-Free Technique On Plaque Retention, White Spot Lesions, And Bracket Failure: A Randomized Clinical Trial, Payam Ishani Afousi

Theses & Dissertations

A side effect of orthodontic treatment is the development of white spot lesions (WSLs). This thesis attempted to evaluate the effects of the use of APC™ Flash-Free (FF) and conventional adhesives in bonding of orthodontic brackets on plaque formation and retention, WSL development, and bracket failure in-vivo. This was accomplished by collecting plaque samples from around orthodontic appliances and analyzing them using ATP-driven bioluminescence; scanning enamel surfaces using the Canary System™ to evaluate WSL development, and counting the number of spontaneous debonding of brackets of the 4 maxillary incisors in the first 6 months of treatment. It was found …

Cervical Spine Angles, Craniocervical Posture, Neck Length, And Oropharyngeal Airway Analyses Of Sleep Apnea Patients In Both Supine And Upright Positions: A Retrospective 3-D Imaging Study, Brian Tuan Luong

Theses & Dissertations

Obstructive sleep apnea (OSA) is one of the most common respiratory disorders. Previous airway studies of OSA subjects have largely relied on 2-D radiographs.

The purpose of this study is to use 3-D imaging to the analyze the relationships among cervical spine angles, craniocervical posture, cervical spine length and the oropharyngeal airway volume in OSA patients in both the supine and upright positions.

Twenty-eight OSA subjects with 3-D imaging were included. Airway, craniocervical posture, spine angles, and spine length were assessed using Dolphin 11.8. Correlation analyses were utilized to detect associations among the recorded and measured variables. Mean differences were …

Barriers To Pediatric Triage Guideline Compliance: A Survey Of Nebraska Emergency Departments, Jonathon J. Gruba

Theses & Dissertations

Nebraska emergency departments may be underprepared for a mass casualty event involving a large number of children, as indicated by the results from the 2013 Emergency Medical Services for Children’s (EMSC) Pediatric Readiness Project (PRP) report. This was primarily evident by the lack of existence of a pediatric triage policy among Nebraska emergency departments. Utilizing a survey, this study attempted to identify the emergency departments in Nebraska that followed the EMSC guideline of having a pediatric triage policy, as well as to identify possible barriers to guideline adherence among those that did not have the policy.

It was found that …

Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang

Theses & Dissertations

Metastasis is the main cause of cancer mortality and morbidity, leading to several million deaths every year. Less than 20% of pancreatic cancer (PC) patients are candidates for surgery due to spread beyond the pancreas. Desmoplasia presents substantial barriers to perfusion, diffusion, and convection of antitumor therapeutics into the PC tissues. We focus on developing novel therapies that regulates tumor microenvironment, chemosensitizing tumor to therapeutics and preventing metastasis.

Gene therapy is emerging as a promising new therapeutic agents for cancer treatment. A targeted, systemic, effective and safe gene delivery system should be developed. CXCR4/SDF-1 axis plays a crucial role in …

Design, Synthesis, And Evaluation Of Aryl Hydantoins And Ureas As Antischistosomal Agents, Chunkai Wang

Theses & Dissertations

Schistosomiasis is a tropical parasitic disease caused by infections with flukes of the genus Schistosoma, affecting as many as 440 million individuals worldwide, with 779 million living at risk of infection. A new drug for schistosomiasis is urgently needed as praziquantel (PZQ) is currently the drug of last resort and the development of resistance cannot be ignored, particularly in view of its large-scale use in many endemic countries. Furthermore, PZQ is active against adult but not juvenile schistosomes; this may be an important factor in the frequently observed treatment ‘failures’ in areas endemic for schistosomiasis.

The introduction of PZQ in …

Identification And Intervention For Action Planning Deficits In Children With Hemiplegic Cerebral Palsy, Swati M. Surkar

Theses & Dissertations

The primary purpose of this investigation was to describe and quantify action-planning deficits during goal-directed movements in children with hemiplegic cerebral palsy (HCP). Three specific topics were addressed: brain activation, kinematics, and the use of visual input. First, we assessed prefrontal cortex (PFC) activation during complex goal-directed actions in children with HCP. The outcome suggested that children with HCP have higher PFC activation than age matched typically developing (TD) children during action planning, potentially due to the difficulty in allocating attentional resources for simultaneously processing the cognitive (i.e., attention, memory, information processing) and motor demands of the goal-directed task. Reduced …

Polymeric Nanocarriers For Delivery Of Small Molecules And Mirnas For The Treatment Of Liver Fibrosis And Pancreatic Cancer, Virender Kumar

Theses & Dissertations

The aim of this thesis is to develop combination therapy of small molecules and miRNAs for treating liver fibrosis and pancreatic cancer. New amphiphilic biodegradable polymers capable of carrying small hydrophobic molecules and hydrophilic anionic nucleic acids were synthesized, characterized and evaluated in vitro and in vivo liver fibrosis and pancreatic cancer mouse models.

In Chapter 1, an overview of liver fibrosis, current treatments and the role of miRNAs in liver fibrosis as well as the design of their delivery systems is given. Further, a general introduction to pancreatic cancer and role of miRNAs in pancreatic cancer is given. In …

The Impact Of Electronic Health Records On Healthcare Service Delivery, Patient Safety, And Quality, Kate Elizabeth Trout

Theses & Dissertations

The HITECH Act has provided over $30 billion of support through the Meaningful Use program to implement Electronic Health Records (EHRs) with aims to improve healthcare service delivery, efficiency, quality, and patient safety. New healthcare models, such as pay-for-performance and value-based purchasing, were envisioned to aligning quality with reimbursement mediated with the use of EHRs. It is unclear of how EHRs and Meaningful Use have impacted health service delivery, patient safety, and quality of care. Thus, making it difficult to determine if the specific set of objectives for Meaningful Use have had a positive impact on outcomes, which ultimately is …

Behavioral Care For Children In Urban And Rural Integrated Primary Care, David I. Taylor

Theses & Dissertations

Mental, emotional, and behavioral issues in children are a significant concern for the children, their families, and society. Despite the existence of evidence-based treatments, the success of behavioral healthcare to meet the needs of these families will require high quality communication and relationships across a wide range of stakeholders. Integration of care represents a patient-centered strategy to unify these stakeholders into a single cohesive care team. The purpose of this dissertation is to define the behavioral healthcare team in integrated primary care for children in terms of the functional roles involved and to evaluate the quality of relationships and communications …

The Effect Of Agricultural Exposures And Genetics On Respiratory Phenotypes, Lisa W. Boyd

Theses & Dissertations

Agricultural workers are at risk for respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and chronic bronchitis, due to exposures and inflammatory agents found in their work environment. While previous studies have been conducted to examine agricultural effects of chronic respiratory diseases more closely, there are still several significant gaps in the existing literature.

This dissertation explores the relationship between agricultural exposures and respiratory diseases. Utilizing two populations, the Keokuk Country Rural Health Study and the AgLung Study, this research: 1) used principal factor analysis (PFA) to distill exposure data into essential variables characterizing long-term agricultural exposures in order …

The Effects Of A Preceptor Coaching Intervention On Use Of Clinical Judgment By New Graduate Nurses, Sue A. Schuelke

Theses & Dissertations

This work attempts to evaluate a preceptor intervention on the development of critical thinking/clinical judgment from the new graduate’s point of view as well as from the preceptor’s point of view. Manuscript 1 is a systematic review of the literature related to preceptor’s interventions and its effect on clinical judgment. Manuscript 2 describes the results of focus group interviews of preceptors and the viewpoint on clinical judgment and related concepts. Results of a pilot study: The effects of a preceptors coaching on new graduates clinical judgement, is reported in Manuscript 3. Each section includes an overview of each manuscript, a …

Role Of B Cell And Hematopoietic Cell Intrinsic Actions Of Erα In Lupus Pathogenesis, Dana E. Tabor

Theses & Dissertations

Lupus is a chronic autoimmune disease characterized by the presence of autoimmune B and T cells and the production of pathogenic antibodies against nuclear antigens. Lupus predominately affects women between menarche and menopause. There are both genetic and environmental risk factors which affect an individuals’ risk of developing lupus. Estrogens are a risk factor for developing lupus and are thought to contribute significantly to the initiation and progression of disease. In lupus-prone mice, genetic knockout of a receptor for estrogen, estrogen receptor alpha (ERα), causes significant attenuation of lupus. Previous studies have not identified the cell type or …

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

The Development Of Transforming Growth Factor-Beta 1 Associated Fibrosis In The Gastrocnemius Of Peripheral Artery Disease Patients And Response To Revascularization And Supervised Exercise Therapies, Duy M. Ha

Theses & Dissertations

Peripheral Artery Disease (PAD) affects over 200 million people worldwide with a 5-year mortality rate as high as 30%. Atherosclerotic blockages impair blood flow to the lower limbs, causing ischemic leg pain and dysfunction upon exercise that later progresses to ulcerations and gangrene and often requires amputation. The standard therapies, revascularization and exercise, allow patients to walk further and longer but are at best maintained short-term. One explanation may be the development of myopathic changes in the limb that progress despite improved hemodynamics—a paradigm shift in the classic view of PAD pathophysiology as solely a mismatch between blood supply and …

Changes To Echocardiography-Derived Left Ventricular Filling Pressures And Cardiac Output In Response To Fluid Boluses In Elderly Patients With Left Ventricular Diastolic Dysfunction Undergoing Vascular Surgery, Sasha K. Shillcutt

Theses & Dissertations

Left ventricular diastolic dysfunction (LVDD) of the heart is a condition where the heart does not relax properly. This condition is important during times of stress, as LVDD is associated with significant morbidity of elderly surgical patients. LVDD is often asymptomatic and unrecognized as many of these patients have normal ejection fractions. However, LVDD may lead to heart failure in patients with preserved systolic function, with the incidence being as high as 50% in hospitalized elderly patients. The diagnosis of LVDD is an independent risk factor for postoperative major adverse cardiac events (MACE) and negatively impacts post-surgery readmission rates. Anesthesiologists …

Antioxidant And Anti-Inflammatory Nutrients On Lung Function In Chronic Obstructive Pulmonary Disease, Jessica M. Hinds

Theses & Dissertations

Introduction Veterans are three times more likely to develop chronic obstructive pulmonary disease (COPD) than the general population. This is likely due to increased use of tobacco and exposure to environmental risk factors. Nutritional intake has been linked to COPD, and veterans report unique barriers to improving their eating habits.

Purpose The primary outcome of this study was to examine the relationship between antioxidant and anti-inflammatory nutrient intake and lung function in veterans with COPD. It was hypothesized that a higher intake of lutein + zeaxanthin, ß-cryptoxanthin, lycopene, retinol, ɑ-carotene, ß-carotene, vitamin C, vitamin D, ɑ-tocopherol, omega-3, zinc and selenium …

Stability And Kinetics Of Dna Pseudoknots: Formation Of T∗A•T Base-Triplets And Their Targeting Reactions, Calliste Steffensmeier

Theses & Dissertations

Pseudoknots have been found to play important roles in the biology of RNA. These stem-loop motifs are considered to be very compact and the targeting of their loops with complementary strands is accompanied with lower favorable free energy terms. We used a combination of spectroscopic (UV, CD and fluorescence), calorimetric (DSC, PPC and ITC) and kinetic (SPR) techniques to investigate: 1) Local base-triplet formation in pseudoknots; 2) energetic contributions for the association of pseudoknots with their complementary strands; and 3) the kinetic rates as a function of targeting strand length.

We investigated a set of DNA pseudoknots with sequence: d(TCTCT …

Leisure Time Physical Activity Preferences, Behaviors, And Hypertension: Evidence From The China Health & Nutrition Survey, 2004-2011, Junmin Zhou

Theses & Dissertations

Background: Physical activity has been continuously declining in China. At the same time, prevalence of hypertension has dramatically increased. The associations between leisure time physical activity preference, behavior, and development of hypertension in Chinese adults remained not fully understood and few studies have examined these associations using longitudinal data.

Objectives: This dissertation examined the interrelationships among leisure time activity preference, behavior, and the incidence of hypertension using longitudinal data from 2004 to 2011 in the China Health and Nutrition Survey. It also assessed the urban-rural disparities.

Methods: A total of 2,687 adults were included in the analysis. Multivariate logistic regressions …

Psychological Aspects Of Head And Neck Cancer, Katherine Rieke

Theses & Dissertations

Patients with head and neck cancer may be at increased risk for depression diagnosis when compared to other cancer sites, both before and after their cancer diagnosis. Behavioral risk factors for head and neck cancers, including tobacco and alcohol use, may be indicative of depression before cancer diagnosis. Further, head and neck cancers and their treatments can cause serious morbidity among patients, including physical disfigurement and loss of function. Additionally, these cancers are often accompanied by social stigma, personal shame, and guilt. While there is a significant body of research examining depression in this cancer population, there are still several …

Assessing Change In Baseline Preparedness Knowledge In Long-Term Care Facilities, Heidi L. Wheeler

Theses & Dissertations

With much of the focus and federal resources in recent history going to support hospital preparedness, long-term care facilities have been left behind even though they house one of our most vulnerable populations. Few regulations and standards have required these facilities to keep pace with preparing for an increasingly volatile environment and aging society. This is changing with the proposal of new federal standards and regulations requiring more thorough and robust preparedness planning. These new requirements do not have to be overwhelming or burdensome to facilities but can be included quite simply into routine planning and training. This study looks …

The Use Of Platelet Rich Fibrin In Pulpal And Periodontal Regeneration, Elisabeth L. Easley

Theses & Dissertations

Purpose: Platelet rich fibrin (PRF) has been postulated to aid in regeneration. Therefore, the purpose of this study is to evaluate the inflammatory response of PRF in vitro, and analyze clinically and histologically the effectiveness of PRF on pulpal regeneration after reimplantation.

Materials and Methods: The in vivo experiment included 18 patients (69 teeth). Teeth were extracted and apicoectomy performed. The tooth was reimplanted and splinted after PRF was condensed into the apex. Control teeth received the same treatment with the exception of the PRF. After 3-11 months, vitality was checked, teeth were extracted and analyzed histologically. For the in …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

The Role Of Inflammatory Monocytes In Post-Influenza Methicillin-Resistant Staphylococcus Aureus Pneumonia, Karl J. Fischer

Theses & Dissertations

Secondary bacterial infections following influenza can lead to poor clinical outcomes and mortality. It is widely accepted that susceptibility to secondary bacterial infections is attributable to a suppressed innate antibacterial immunity. In contrast, a dysregulated host inflammatory response may also contribute to disease severity. Inflammation induced by viral infection alone significantly affects lung pathology, potentially exacerbating the destruction of the respiratory tract. Interestingly, the role of inflammatory mediators such as inflammatory monocytes have been extensively studied during influenza infection alone; however, their role during secondary bacterial infection are still not fully established. The objective of this study was to analyze …

Surveillance Of Non-Fatal Agricultural Injuries Among Farm Operators In The Central States Region Of The United States, Ketki Patel

Theses & Dissertations

Agriculture is a major industry in the U.S. with high rates of fatal and non-fatal occupational injuries. The dynamic nature of the U.S. agriculture industry, regional variations in farming practices, and the diverse workforce make surveillance of injuries challenging. A recent National Academies (U.S.) evaluation reported that data for non-fatal agricultural injury are scarce, and mainly available through national surveys. Limited data are available for employees in the agriculture sector, especially farm owners and operators. The objectives of this study were to- 1) review and evaluate existing survey-based systems for surveillance of non-fatal agricultural injuries on U.S. farms, and 2) …