Investigative Techniques Commons^™

Development, Validation, And Testing Of A Novel Ergonomic Backpack, Lyndsey Kate Bouve

Theses and Dissertations (ETD)

Backpacks (BP) are one of the most common means for carrying loads but the loading mechanics that result from carrying heavy loads can have implications across the body. It has been suggested that loads in a BP should not excess 10-15% of the user’s body weight (BW) but that is not always feasible. The loads in a BP are transferred to the body via the shoulder strap which induce a shear and compressive force which act externally on the spine and transfer loads through it to the lumbar. Additionally, the weight of the bag induces an external moment that further …

The Effects Of Synovial Fluid And Inflammatory Cells On Orthopaedic Implant Alloys, Lisa Phan

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) is a common surgical procedure used to treat end-stage osteoarthritis. The implants used in TKA typically consist of a Cobalt Chromium Molybdenum (CoCrMo) femoral component and a Titanium Aluminum Vanadium (TiAlV) alloy baseplate. These metal alloys are chosen for their mechanical properties, corrosion resistance, high affinity for bone, and biocompatibility. However, they can be susceptible to mechanical and electrochemical wear, leading to the release of metal ions. Osteoarthritis and inflammation can alter the composition of Synovial Fluid (SF), potentially causing implant corrosion and the release of metal ions into the surrounding tissue. These metal ions …

Tcf4 Is A Key Mediator Of Cell Identity And Oncogenesis In Neuroblastoma, Nour Aljouda

Theses and Dissertations (ETD)

Neuroblastomas (NB) are embryonal childhood tumors that derive from the multipotent neural crest cells (NCCs) of the peripheral nervous system. NB accounts for more than 15% of all childhood cancer-related deaths. Despite the most intensive multimodal therapy, more than 50% of patients with high-risk NB relapse with often fatal, resistant disease. Novel therapies are desperately needed to improve cure rates. Previous studies proposed that the deregulation of normal neural crest developmental programs contributes to NB oncogenesis by retaining the highly migratory and proliferative traits of NCCs. Thus, activation or repression of neural crest developmental pathways have been implicated in NB …

A Comparative Analysis Of Human Insulin Versus Analog Insulin: Glycemic Control, Adherence, Utilization, And Cost-Effectiveness, Sohul Ahmed Shuvo

Theses and Dissertations (ETD)

Background: Despite being a lifesaving medicine for many patients with diabetes, insulin cost is growing out of reach for many. Of the two broad classes of insulin available in the US, analog insulin is newer, costlier, and more widely used than human insulin. The new mode of delivery with pen devices has shown promise in improving adherence and achieving glycemic control and gaining popularity. But comparing adherence to different insulins is challenging due to the lack of a validated insulin adherence method. Very little is known about the comparative benefits of different insulin types and different modes of delivery in …

Inhibition Of Kdm4 With Qc6352 To Target High-Risk Neuroblastoma, Ahmed M. Abuzaid

Theses and Dissertations (ETD)

Neuroblastoma (NB) is a malignancy of improperly maturated nerve tissues of the sympathetic nervous system. It is the most diagnosed extracranial solid tumor of childhood, and it accounts for roughly up to 10% of all childhood malignancies and 15% of all childhood malignancy-related deaths. MYCN amplification, occurring in 20-25% of all NB patients and 50% of all high-risk NB patients, is the well-characterized genetic abnormality and is associated with ill-fated outcomes. Regrettably, in spite of the contemporary therapeutic advances and aggressive combinatorial treatments, the overall 5-year event-free survival rate is roughly 51% with a 5-year overall survival rate of nearly …

Pkpd-Model Based Preclinical Characterization Of The Activity Of Spectinamide 1599 Against Mycobacterial Subpopulations. And The Identification Of Potential Partners For Combination Therapy, Zaid Hanif Temrikar

Theses and Dissertations (ETD)

Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent prior to COVID19. Mycobacterium tuberculosis (Mtb) is the causative agent of TB. The interaction between Mtb and the immune system leads to development of diverse environmental niches and physiology within the lung of the TB patients. Mtb is thought to adapt and thrive in such an environment by transforming to different phenotypic variants. Such variants are difficult to kill and are thought to prolong TB pharmacotherapy. Spectinamide 1599 is a synthetic modification of spectinomycin that has demonstrated excellent …

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …

Investigation Of Clinically Relevant Fluconazole Resistance Mechanisms In The Fungal Pathogen Candida Parapsilosis, Laura Anne Doorley

Theses and Dissertations (ETD)

Invasive candidiasis is a severe fungal infection associated with significant morbidity and mortality, particularly among the critically ill and immunocompromised. Candida parapsilosis is the most common non-albicans species causing invasive Candida infections in pediatric and neonatal populations worldwide and is particularly common in the countries of South America, Western Asia, Mediterranean Europe, and Southern Africa. For many of these countries, fluconazole and other triazoles are the first line antifungal agents used for effective treatment of invasive Candida infection. Until recently, rates of fluconazole resistance among C. parapsilosis isolates were relatively low, therefore the determination of clinically relevant resistance mechanisms in …

Molecular And Cellular Investigations Of Prader-Willi Syndrome, Anna K. Victor

Theses and Dissertations (ETD)

Prader-Willi syndrome (PWS) is a complex multigenic neurodevelopmental disorder resulting in hypotonia, developmental delay, hypogonadism, sleep dysfunction and childhood onset obesity affecting 1 in 10,000 to 30,000 individuals. PWS is an imprinting disorder that is caused by a loss of expression of maternally imprinted genes in the 15q11.2-q13 region including NDN, MAGEL2, SNRPN/SNURF, and a cluster of snoRNAs. The majority of cases are caused by inheriting a paternal allele deletion of this region (65-75%) and a smaller number are caused by chromosome 15 maternal uniparental disomy (UPD) (20-30%) or imprinting center defects (1-3%). Here, we used dental pulp stem cells …

Modulation Of Cerebral Artery Smooth Muscle Bk Channel Function By Neurosteroids, Kelsey Caroline Cleland North

Theses and Dissertations (ETD)

Voltage-gated and Ca2+ activated K+ channels of large conductance (BK) channels are essential for many key physiological processes, such as controlling the contraction of smooth muscle, including cerebrovascular smooth muscle. Importantly, BK channels are made up of a homotetramer of α subunits which associate with accessory β subunits. These β subunits alter the activity of the channel; this modulation is subunit-specific. Moreover, these accessory subunits have tissue-specific expression, such that the β1 subunit is highly expressed within cerebrovascular smooth muscle and greatly increases the open probability of BK channels. Increased BK channel open probability is linked to increased dilation of …

Vascular Mechanisms Of Rhabdomyolysis-Induced Acute Kidney Injury, Jeremiah Moyinolu Afolabi

Theses and Dissertations (ETD)

In patients with rhabdomyolysis, the overwhelming release of myoglobin into circulation is the primary cause of kidney injury. Myoglobin causes direct kidney injury as well as severe renal vasoconstriction. An increase in renal vascular resistance (RVR) results in renal blood flow (RBF) and glomerular filtration rate (GFR) reduction, tubular injury, and acute kidney injury (AKI). The mechanisms that underlie rhabdomyolysis-induced AKI are not fully understood but may involve the local production of vasoactive mediators in the kidney. Myoglobin stimulated endothelin-1 (ET-1) production in proximal tubular cells, an effect driven by NADPH oxidase-dependent oxyradical generation. Rats subjected to glycerol-induced rhabdomyolysis also …

Multimorbidity In Diverse Populations: Stratified Analysis Of Race/Ethnicity, Age, Obesity, And Healthcare Costs, Manal Alshakhs

Theses and Dissertations (ETD)

This research aims to fill an essential gap in understanding how Body Mass Index (BMI) cutoffs relate to multimorbidity across races in the United States (US). Given the significant and growing rates of obesity and multimorbidity, as well as the known differences in healthy fat distribution among different races, this is an important area of research. BMI is a widely used but imperfect measure of obesity, as it does not account for differences in body composition. However, it is still used as a diagnostic tool. It is vital to ensure that the cutoffs used to define obesity are appropriate for …

Impacts Of Habitat, Resource Addition, And Predator Exclusion On Rodent Community Structure And Hantaviruses In The Neotropics, Briana Spruill-Harrell

Theses and Dissertations (ETD)

Understanding how climate and human land use change impacts trophic interactions is essential in the face of ongoing biodiversity loss and the continued emergence of RNA viruses and zoonosis. Human land use changes such as agricultural expansion, deforestation, and habitat degradation all have been linked to zoonotic disease emergence. Despite these commonalities, our mechanistic understanding of what drives them is lacking. Moreover, genomic surveillance in wildlife populations is critical for risk assessment and mitigation. Herein, using data collected from field studies within the Reserva Natural del Bosque Mbaracayú (RNBM), a protected area of the Interior Atlantic Forest (IAF), I examined …

Transmission Competence Of B. Burgdorferi Infected Ixodes Ticks And Development Of An Ospc-Based Lyme Disease Vaccine, Samanta Kamalika

Theses and Dissertations (ETD)

Introduction. Lyme disease, otherwise called Lyme borreliosis, is a vector-borne infectious disease caused by the spirochete Borrelia burgdorferi (Bb). Studying the increase in overall Lyme disease incidence requires understanding the role of the vector Ixodes scapularis (I. scapularis) as the agent that carries the spirochete which is important to limit the occurrence of Lyme disease. Once we understand the vector-pathogen response, it also becomes important to determine the remedies for Lyme disease. Lyme disease can be treated with antibiotics if detected early, but the major obstacle lies in the early detection process. Therefore, it is important to investigate alternative preventive …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Comparison Of A Dynamic Ankle Orthosis To A Walking Boot For Preserving Ankle Joint Motion And Reducing Tibial Bone Load And Strain, Perri Johnson Jr.

Theses and Dissertations (ETD)

Tibial stress fractures are a common overuse injury accounting for 21.9 – 69% of stress fractures among runners and 24 – 51.2% of stress fractures in military cadets. Current treatment involves wearing a walking boot for 3 – 12 weeks, which limits ankle motion and causes lower limb muscle atrophy. A Dynamic Ankle Orthosis (DAO) provided a distractive force that offloaded the ankle and retained sagittal ankle excursion during walking. It remains unclear how tibial loading is affected by a walking boot or the DAO. This thesis presents a feasibility study confirming the offloading effects of the DAO on tibial …

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

The Uncertainty And Psychological Health Of Family Caregivers Of Patients With Delirium In Intensive Care Units, Amal Shokri Haji Assa

Theses and Dissertations (ETD)

Each year, more than 5 million patients are admitted to an intensive care unit (ICU) in the United States, and up to 80 % of these patients develop delirium. Delirium is a common indicator of acute brain dysfunction in the ICU and a predictor of mortality, longer ICU/hospital stay, and long-term cognitive impairment. Family caregivers are a valuable resource in preventing, detecting, and managing delirium in the ICU. However, witnessing delirium episodes can generate adverse psychological symptoms in family caregivers that may compromise their health and well-being. Research in this area has demonstrated a gap in the literature regarding how …

Methods Development In Inflammatory Bowel Disease, Andrew B. Steimke

Theses and Dissertations (ETD)

Inflammatory bowel disease (IBD) is a disease that is classified into two subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). Symptoms can range from mild discomfort to requiring surgical intervention and affects approximately 1-in-200 adults in America alone, with global incidence rates increasing. While many treatments exist for IBD, perhaps the main reason for the lack of a cure is that there are many different pathogeneses that all lead to a very similar expression of symptoms. Over 240 IBD loci have been identified to date, yet the causative allele that drives the association has only been identified in ~60 of …

Nursing Perspectives And Opinions On Early Or Delayed Sepsis Treatment: A Mixed Methods Approach, Pamela L. Harris

Theses and Dissertations (ETD)

Purpose. Each year at least 1.7 million adults in America develop sepsis. Sepsis can lead to life threatening organ dysfunction, severe hypotension, and death when severe sepsis or septic shock is involved. Sepsis is responsible for 50% of acute kidney injury (AKI), which is the most common form of organ dysfunction seen in critical care. Sepsis associated AKI results in loss of, or decreased renal function, is associated with adverse long-term outcomes, and carries a higher mortality rate than non-septic AKI, sepsis without AKI, or septic shock without AKI. Surviving sepsis guidelines suggests a 1-hour window from the time of …

Inflammatory Response Following Hemorrhagic Stroke: The Role Of Cytokines, Patrick Devlin

Theses and Dissertations (ETD)

Hemorrhagic stroke is a dangerous form of stroke resulting from the rupturing of weakened blood vessels, releasing blood that increases intracranial pressure and causes the death of surrounding tissue. Treatment options are improving but remain limited, as evidenced by this condition being characterized by high rates of mortality as well as long-term morbidity. Unregulated inflammatory responses that occur following injury may be partially to blame for these poor outcomes. In response to any injury, the immune system releases cytokines to recruit immune cell activation and promote inflammation. But after hemorrhagic stroke, whether aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH), …

Associations Between Postpartum Depression And Child Overweight And Obesity: Mediating Effect Of Maternal Feeding Behaviors And Beliefs, Michelle Harrison

Theses and Dissertations (ETD)

Purpose. Postpartum depression (PPD) is a mental condition that significantly affects 10% to 25% of women within the first year after the birth of their child. The mother-infant relationship is key to child growth. Previous studies have shown that PPD has a detrimental effect on children’s physical and psychological well-being as it affects the child through the mother’s parenting behavior. Depressed mothers show a lack of engagement with their children, which could extend to feeding practices influencing weight gain. The prevalence and severity of childhood overweight and obesity is a global public health problem. An increase in weight gain in …

A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer

Theses and Dissertations (ETD)

Real-world conversations are often accompanied by some sort of interference that challenges the clarity of the speaker’s message, causing listeners to exert more effort to understand speech. Previous research has demonstrated that when listening to speech becomes difficult, various regions of the brain are recruited beyond those which engage during optimal listening conditions. However, the neural correlates that underly listening effort are not fully understood. Importantly, the pupillary response can be used to index listening effort, such that pupil size increases with increasing cognitive demand. I proposed that pupillometry can be used to characterize the cortical response, such that changes …

Predictors Of Hyperkalemia And Outcomes Of Dyskalemia In Us Veterans With Advanced Chronic Kidney Disease Transitioning To Dialysis, Ankur Dashputre

Theses and Dissertations (ETD)

Background: The kidneys play a crucial role in maintaining homeostasis of serum potassium levels (K+). Patients with advanced chronic kidney disease (CKD) are at a higher risk of experiencing dyskalemia events (i.e. hyper- and hypokalemia; especially the former) and thus future adverse outcomes. Currently, there is a dearth of literature on prediction models for hyperkalemia and the effects of dyskalemia on outcomes such as incidence of ischemic stroke and short-term hospital/emergency room (ER) utilization in an advanced CKD population transitioning to dialysis. Objectives: Using a nationally representative sample of US veterans with advanced CKD transitioning to dialysis, in the pre-dialysis …

The Relationship Of Child Health And Parenting Stress To Child Neurocognitive Development, Nancy Alise Farrell

Theses and Dissertations (ETD)

Problem. Although the United States rates high in economic resources, the neurocognitive development (NCD) of children falls behind many other developed nations. Levels of parenting stress may be linked to sociodemographic factors such as the high incidence of poverty in children or health disparities in children, which in turn may affect NCD in children. Using the data from an observational, longitudinal cohort study of a diverse population could provide information related to parenting stress, child health, and related factors to guide and support interventions with families and policies to improve child NCD. Aims. The overall aim of this study was …

Developing Deep-Learning Methods For Diagnosis And Prognosis Of Pediatric Progressive Diseases Using Modern Imaging Techniques, Mahdieh Shabanian

Theses and Dissertations (ETD)

Purpose and Rationale. Central nervous system manifestations form a significant burden of disease in young children. There have been efforts to correlate the neurological disease state in tuberous sclerosis complex (TSC) neurological disease state with imaging findings is a standard part of patient care. However, such analysis of neuroimaging is time- and labor-intensive. Automated approaches to these tasks are needed to improve speed, accuracy, and availability. Automated medical image analysis tools based on 3D/2D deep learning algorithms can help improve the quality and consistency of image diagnosis and interpretation for cognitive disorders in infants. We propose to automate neuroimaging analysis …

Identifying The Molecular Cause Of Extreme Endoplasmic Reticulum Dilation In Pediatric Osteosarcoma And Its Relationship To The Disease, Rachael Wood

Theses and Dissertations (ETD)

Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology …

Ecology Of Hantaviruses In Rodent Reservoirs And Their Early Innate Immune Responses In Human Model Systems, Evan Peter Williams

Theses and Dissertations (ETD)

The spillover of zoonotic RNA viruses is responsible for a great deal of the disease outbreaks in human populations. These spillover events are set to continue due to anthropogenic and environmental changes that impact the distribution of these viruses. The viruses in the family Hantaviridae are classified as one of these emerging zoonotic RNA viruses. The spillover of the viruses in this family are responsible for two severe human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These viruses are distributed across the globe and are responsible for a large number of human disease cases with …

Examination Of Antiviral Resistance In Venezuelan Equine Encephalitis Virus, Jasper Lee

Theses and Dissertations (ETD)

Venezuelan equine encephalitis virus (VEEV) is a New World Alphavirus that causes Venezuelan equine encephalitis (VEE), which is characterized by a febrile illness that can progress to neurological disease and death. While no major outbreaks of VEE have occurred since 1995, VEEV is a virus of concern as, in addition to its spread through mosquitos, it can be aerosolized and used as a bioweapon. Unfortunately, there are currently no FDA-approved vaccines or antivirals against VEEV. Efforts have been made to discover small molecules with an inhibitory effect on VEEV, but the potential for emergence of antiviral resistance to these compounds …

Responding To The Pandemic: A Multicountry Study On Social-Political Factors And Health Outcomes Of Covid-19, Lan Yao

Theses and Dissertations (ETD)

Introduction. Coronavirus Disease 2019 (COVID-19) poses a major global threat to human beings, which has caused devastating consequences of population health, political, and economic crises in many countries. This dissertation was composed of three research activities to study the following aims: (1) review the existing literature focusing on political factors and health outcomes of COVID-19; (2) assess the relationship between democracy and case fatality rate of COVID-19 by controlling for the effect of age, comorbidity, health expenditure, healthcare workforce, and population density; and (3) identify the trajectory pattern cases peak days, deaths peak days, and peak periods.

Methods. We accessed …