Medicine and Health Sciences Commons^™

Identifying Micrornas Panel Associated With Hepatocellular Carcinoma In Serum Of Chronic Hepatitis C Patients, Areeg Dabbish

Theses and Dissertations

Introduction: early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this poorly diagnosed widely-spread disease. Dysregulation in microRNA (miRNAs) expression is associated with HCC progression. Objective: Is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Methodology: Candidate miRNAs were selected using bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE- miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424 and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV and 72 HCV-associated …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira

Arts & Sciences Electronic Theses and Dissertations

At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …

Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid

Arts & Sciences Electronic Theses and Dissertations

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …

The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil

Arts & Sciences Electronic Theses and Dissertations

ATP-sensitive potassium (KATP) channels link cellular metabolism and membrane excitability in many tissues, including brain and pancreas. Gain-of-function (GOF) mutations to KATP channels cause neonatal diabetes, with some patients exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Diabetic symptoms have been attributed to loss of membrane excitability and insulin secretion in pancreatic β-cells, though the origin of neurological deficits and the effects of neuronal KATP-GOF mutations more generally remain elusive. In this dissertation, I will present evidence that mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited predominantly learning and memory deficits. …

Impact Of Theory-Based Interventions On Meaningfulness Of Undergraduate Nursing Pharmacology Student Learning, Betsy L. Mauldin

Nursing Theses and Dissertations

Objective: Nursing pharmacology is a complex and content-dense course, often cited as difficult for nurse educators and students and a reason for not progressing in nursing curricula. Even nurses who experience high academic performance report feeling ill-prepared to adequately perform medication management for nursing practice in the current fast-paced environment. The objective of this five-chapter portfolio is to explain the development and implementation of a two-pronged intervention to facilitate meaningful learning of pharmacology principles within nursing students. Chapter 1 describes an overview of the approach to the intervention.

Methods: Chapter 2 describes one prong of the study intervention, the Pharmacology …

Antimicrobial Activity Of Bacterial Virus Components: An Empirical Investigation Of The Killing Capacity Of Toxins From Burkholderia, Kyle Walny

Honors Projects

Given the growing issue in healthcare of antibiotic resistance, effective and safe alternative treatment methods are required. One of these possible alternative treatment methods is bacteriotoxins including bacteriocins and tailocins. The focus of this study is a bacteriotoxin from Burkholderia cenocepacia (ATCC 25608), which was induced for toxin using a modified UV light induction procedure and tested against a variety of Pseudomonas and Burkholderia for its killing capacity. Various other pathogenic strains were then induced with UV light and tested. The results showed that the toxin from ATCC 25608 was very effective against most of the Burkholderia tested and warrants …

How Can Stem Retention Rates At Bgsu Be Increased Both In And Out Of The Classroom?, Josalyn A. Coffee

Honors Projects

Previous research in STEM student retention rates showed a gap in knowledge regarding why this group of student experience higher rates of burnout than other groups of students. This study investigated the barriers STEM students at BGSU experienced. A survey was sent out to STEM and non-STEM students alike that asked questions regarding student’s personal history before attending BGSU, their course experiences at BGSU, and the levels of support they have outside of BGSU. The survey data showed that there was little difference in the rates that students switch majors solely based on being in the STEM field. The data …

Examining The Need For Parental Satisfaction With The Msu Extension Equine Assisted Therapy Program, Ashlyn Ann Kiker

Theses and Dissertations

Animal assisted interventions are becoming more prevalent in our society. Animal interventions have become a popular therapy technique that exist to aid a variety of disabilities. Equine therapeutic riding has become one of the most popular forms of animal assisted therapy for both children and adults. While research shows the importance and benefits of animal assisted therapy for children, there is a lack of research concerning parental satisfaction within therapeutic riding programs.

This study tested a newly developed instrument for measuring parental satisfaction for therapeutic riding programs. The Parent/Caregiver Evaluation Tool (Kerr, 2021) was administered to parents/caregivers whose children participated …

An Investigation Of Chronic Pain As A Much-Neglected Symptom Of Hypermobile Ehlers-Danlos Syndrome, Sydney Collins

Honors Theses

Ehlers Danlos Syndrome is a group of heritable loose connective tissue disorders with 13 distinguished subtypes. The hypermobile type of Ehlers Danlos Syndrome (hEDS) is the most common subtype and is caused by a genetic mutation that leads to defective collagen fibrils. This leads to joint instability and hypermobility, skin elasticity, widespread pain, fatigue, and generalized tissue fragility. Chronic pain is reported to be a symptom in as high as 92% of the hEDS population (Voermans et al., 2010); despite this prevalence, there is a significant lack of research, awareness, and treatment standardization regarding pain in hEDS. This literature review …

A Review Of Calcineurin Biophysics With Implications For Cardiac Physiology, Ryan B. Williams

Theses and Dissertations

Calmodulin is a prevalent calcium sensing protein found in all cells. Three genes exist for calmodulin and all three of these genes encode for the exact same protein sequence. Recently mutations in the amino acid sequence of calmodulin have been identified in living human patients. Thus far, patients harboring these mutations in the calmodulin sequence have only displayed an altered cardiac related phenotype. Calcineurin is involved in many key physiological processes and its activity is regulated by calcium and calmodulin. In order to assess whether or not calcineurin contributes to calmodulinopathy (a pathological state arising from dysfunctional calmodulin), a comprehensive …

Investigating A Novel Receptor That Mediates Vasoconstriction In Mouse Femoral Arteries, Joselia Carlos

Electronic Thesis and Dissertation Repository

The synthetic peptide trans-cinnamoyl-leucine-isoleucine-glycine-arginine-leucine-ornithine-amide (tcLIGRLO) causes smooth muscle contraction in mouse femoral arteries. The identity of the receptor that mediates this response is undetermined. We hypothesize that the novel mechanism for tcLIGRLO-induced contractions involves a G-protein coupled receptor (GPCR) and a G_q-Ca²⁺ signalling pathway. Chapter 2 describes experiments using femoral arteries isolated from male and female systemic protease-activated receptor 2 (PAR2KO) mice (n=31; 21 – 39 weeks of age) using tcLIGRLO and the G_q-inhibitor, YM-254890 (YM). Contractions produced by tcLIGRLO did not differ by sex but decreased as age increased. YM inhibited tcLIGRLO-induced contractions. Chapter …

Genomic Epidemiology Of Clostridium Difficile Colonization And Transmission In An Intensive Care Unit Cohort, Brianne Ciferri

Dissertations and Theses

Abstract

Genomic epidemiology of Clostridium difficile colonization and transmission in an intensive care unit cohort

by Brianne Ciferri, MPH

Advisor: C. Mary Schooling, PhD

Introduction: Clostridiodes difficile (C. difficile) is a leading cause of healthcare associated infections (HAI) in the United States and responsible for an estimated incidence of 223,900 cases and 12,800 deaths per year^1,2. C. difficile can cause gastrointestinal illness with symptoms ranging from mild diarrheal illness to a life-threatening condition. C. difficile is an opportunistic pathogen in which spores can live in an undisturbed dormant state within the intestinal tract and become …

Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan

Electronic Thesis and Dissertation Repository

Kindlin-1 is a scaffold protein linking the cytoskeleton to the extracellular matrix. Loss of function mutations in the FERMT1 gene (encoding Kindlin-1) cause gastrointestinal and skin defects associated with increased susceptibility to aggressive epidermal squamous cell carcinoma (SCC). This study investigated the consequences of targeted FERMT1 inactivation in the SCC-13 cell line of epidermal SCC. My studies demonstrate Kindlin-1 is not essential for SCC-13 proliferation or clonogenic potential in culture. Kindlin-1 was required for cell spreading on collagen I, but not on laminin-332, and its absence enhanced SCC-13 directional migration. Finally, I identified several proteins involved in tumor formation and …

Atrx Inactivation And Idh1-R132h Drive Preferential Sensitivity To Proton Vs. X-Ray Radiotherapy In Glioma Stem Cells, Ángel Adrián Garcés

Dissertations & Theses (Open Access)

Background: Glioma Stem Cells (GSCs) are self-renewable, treatment resistant cells in the glioma tumor mass known to promote tumor development. In contrast to traditional photon-based radiation therapy (XRT), proton radiation therapy (PRT) may induce more complex DNA damage and therefore might have the potential to eliminate GSCs. Although previous studies have individually linked IDH mutations, specifically IDH1^R132H, and ATRX inactivating mutations to improved patient outcomes and suppressed DNA damage repair compared to their respective wild-types, the mechanisms by which these two genetic alterations interact in GSCs treated with PRT compared to XRT are currently unknown. We hypothesize that …

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations & Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …

Effects Of Seat And Axle Position On Pain, Pathology, And Independence In Pediatric Manual Wheelchair Users With Spinal Cord Injury, Hannah Frank

Theses and Dissertations

Manual wheelchair (MWC) users with spinal cord injury (SCI) rely heavily on their upperextremities to complete daily occupations. Due to repetitive shoulder use during wheelchair mobility and propulsion, MWC users are at greater risk of shoulder pain and shoulder pathology, and thus decreased independence, and lower quality of life. The relative fit of the wheelchair and its parameters are critical and can further impact the user’s propulsion biomechanics. Parameters such as seat angle and axle position may put the user in detrimental shoulder positions for longer periods of time, impacting health outcomes even more. Although the effects of wheelchair setup …

(R)-2,5-Dimethoxy-4-Iodoamphetamine [(R)-Doi] Influences Coping Strategies To An Escapable Social Stress, Kevin Thomas Krupp

Dissertations and Theses

Depressive mood disorders are a leading cause of disability worldwide and pharmacological treatments for these disorders are inadequate, requiring new compounds with greater efficacy be investigated. The etiology of depression is heterogeneous; however, it is well established that stress exposure, and the proinflammatory effects of stress have a major role. Psychedelic compounds have rapid and long-lasting anxiolytic and antidepressive effects in humans and animal models of stress induced affective behavior. However, it is not completely understood how these compounds produce such rapid effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A partial agonist with potent anti-inflammatory properties, …

Examination Of The Association Between C - Reactive Protein(Crp) And Covid-19 Infection Severity And Length Of Hospitalization, Abdulahi Aremu Ayanwale

Open Access Theses & Dissertations

Chronic stress can lead to many systemic complications and low-grade systemic inflammation including increased levels of inflammatory cytokines, such as C-reactive protein (CRP). CRP is a marker of systemic inflammation and is associated with depression and perceived stress. Elevations can result in ineffective immune responses, thereby increasing the risk of complications and mortality from infections. Recent evidence suggests that uncontrolled inflammatory responses associated with COVID 19 are a major determinant of disease severity.  The COVID 19 is transmitted from one person to another through droplets from coughing, sneezing, talking, touching droplets on surfaces and contamination by hand-to-mouth routes. The mechanism …

Impact Of Fish Oil On Intestinal Permeability, Inflammation, And Performance In Swine, Anthony Fernando Alberto

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Our research examined the effects of fish oil supplementation on intestinal permeability, systemic inflammation and performance in piglets. An lipopolysaccharide (LPS) challenge was done to stimulate the synthesis and release of the cytokines, in an effort to mimic the immune response that piglets would have when facing stress or pathogen challenge. Fish oil increased feed intake but did not affect growth when compared to control. Total fatty acid digestibility increased by 6% when fish oil was included in the diet. Also, we observed a 16% increase on 16-carbon fatty acids digestibility. Fish oil did not affect the plasma …

Impact Of Xenobiotics On Neuronal Outcomes, Gabriela Henriquez

Open Access Theses & Dissertations

Neurodegenerative diseases are a common affliction of the Central Nervous System. They are caused by age, genetics, and environmental factors. Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are well-known among the host of neurodegenerative disorders, with Alzheimer's disease and Parkinson's disease being the leading pathologies across this canvas. It is known that the pathogenesis of neurodegenerative diseases is multifactorial due to the involvement of genetic mutations, radical-induced protein damage, abnormal aggregation of misfolded proteins, and the formation of amyloid deposits. The amyloid proteins in neurodegenerative disease include Tau and Amyloid (Aβ) in Alzheimer's disease and α-Synuclein in …

Evaluation Of Two Neonatal Challenge Models For Broiler Chickens And Their Effects On Early Performance Parameters, Callie Selby

Graduate Theses and Dissertations

Formaldehyde fumigation in poultry hatch cabinets has been utilized for sanitation of hatching eggs for over a century. Formaldehyde is utilized to minimize pathogenic microbes on the surface of the egg as well as the microbial bloom during the hatching process. While formaldehyde is effective, its use is regulated in the United States and Europe due to its carcinogenic nature. Formaldehyde has been shown to damage the cuticle of the egg, cause embryonic death, and damage the epithelial lining of the respiratory tract of freshly hatched chicks, predisposing them for respiratory infection. Alternatives for formaldehyde fumigation must be identified and …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

Examining An Intersection Of Environmental Justice And Covid-19 Risk Assessment: A Review, Ashley Ellis

Honors Theses

This study views the risks associated with the novel coronavirus (COVID-19) as an environmental injustice issue due to the connection between existing environmental disparities and the disproportional negative impacts brought upon by the virus. The social and health determinants attributed to those environmental disparities have traditionally been evaluated as individual risk factors, an approach that fails to gauge the complexity of an environmental injustice issue. This study employs the emerging theory of intersectionality, a belief that phenomena cannot be linked to one principal cause but instead an interconnected web of influences, in order to synthesize the multitude of factors believed …

Discerning The True Dilemma Of Diabetes Among Hispanics, Ramon Ponce

Nursing | Senior Theses

There is a common misconception that the primary role of nurses is to follow doctors’ orders and treat patients who are currently suffering and experiencing pain. Chronic illnesses such as diabetes can be prevented and better managed if the population who is greatest at risk is better informed and educated on the disease. Different cultures and ethnicities have different foods that unfortunately puts them at risk to get diabetes. Hispanics typically follow a diet that is high in carbohydrates, saturated fats, and sugars that greatly contribute to the development of diabetes. Often, Hispanics are not educated enough to comprehend the …

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations & Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

Evaluating The Biological Activities Of Novel Histone Deacetylase Inhibitors (Hdaci) In Adherent And Nonadherent Tumor Cell Lines, Samer Alanani

Theses and Dissertations

Epigenetic dysregulations are linked to many human diseases including neurodegenerative disorders, immunodeficiencies, cardiac disease, and most notably cancer. Changes in the mechanisms of histone modifications have been recognized as hallmarks of carcinogenesis. One of these modifications is histone acetylation which is regulated by the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The reversible actions of these enzymes govern the acetylome and maintain its balance allowing for activation and repression of gene transcription. However, aberrant overexpression of HDACs in certain tumors is associated with decreased levels of transcription leading to tumor progression and survival. Hence, small-molecule histone deacetylase inhibitors …

Axon Initial Segment Morphology Across Typical Cortical Development And In Mouse Models Of Neurodevelopmental Disorders With A High Incidence Of Epilepsy, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) are commonly associated with a high incidence of epileptic seizures which result from excessive firing of neurons. The axon initial segment (AIS) is a neuronal compartment essential for the control of activity patterns of neurons. The AIS undergoes important modifications during development, but the molecular mechanisms that affect the development, morphology, and protein composition of the AIS are still not well understood. We examined AIS morphology of medial prefrontal cortex (mPFC) pyramidal neurons in wildtype mice across development and in two mouse models of NDDs. Results indicate restructurings at the AIS during typical development, some of which …

Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …