Medicine and Health Sciences Commons^™

Utilizing Bloodless Medicine To Decrease Infection Rates In Hematopoietic Stem Cell Transplantation: A Literature Review, Samantha Saint Fort

Honors Undergraduate Theses

Aim: To determine if a significant relationship exists between bloodless medicine practices and decreased infection rates in oncology patients following hematopoietic stem cell transplantation by performing a literature review.

Background: It is not uncommon for healthcare professionals to encounter Jehovah's Witnesses (JW) seeking medical treatment in the acute care hospital setting and outpatient clinics alike. However, JW's pose a unique challenge to healthcare providers. Their refusal of blood transfusions makes them a population of interest within the medical community. The refusal of blood transfusions also poses a serious challenge to successful treatment in oncology JW patients, and many hospitals will …

Plasmonic Sensor Based Detection Of Dopamine, Sang Lee

Electronic Theses and Dissertations, 2020-

With a rapidly ageing population, neurological diseases are becoming increasingly relevant in the design of public health policies and strategies in western societies. In the last decades, biochemical research has consistently shown the critical role that neurotransmitters and their associated metabolites play as biomarkers in tracking and diagnosis of different brain disorders and cancers. In particular, dopamine, an organic electrochemical neurotransmitter, has been shown to be paramount for the proper functioning of the neural system. Dopamine's dysfunction, has been shown to underlie the pathogenesis in several neurological disorders such as Parkinson's disease, depression, chronic schizophrenia and psychosis. Unfortunately, currently available …

A Retrospective Dosimetry Comparison To Define Uncertainties Found In A Novel Intensity Modulated Electron Therapy (Imet) Treatment Technique For Use In Radiation Therapy, Marco A. Masciantonio

Honors Undergraduate Theses

This study will investigate the difference in radiation at different volumes between traditional electron beam therapy and a novel IMET. The difference in dose will be recorded between the novel IMET and the IMET with a slight shift in the target area. The percent difference between this new model treatment and the model treatment with a shift will be calculated. The main goal of this project is to determine if the target area is still sufficiently treated with this slight shift of the patient in different directions. The percent difference is crucial for the success of this project. It will …

A Systematic Review And Meta-Analysis Of The Relationship Between The Creb Protein's Neuroplastic Functions And The Implications In Neurodegenerative Diseases: A Possible Link Between Synaptic Plasticity And Neurodegenerative Diseases, Mani Sarmast

Honors Undergraduate Theses

In this two-part study, I investigated whether the cyclic-adenosine monophosphate response element-binding (CREB) protein has the potential to be clinically modulated as a therapeutic target for the treatment of neurodegenerative diseases. Part one consisted of a systematic review that was conducted on select articles gathered through a stepwise method to explore (1) the relationship between diseased, neurodegenerative brains and levels of active, phosphorylated CREB (pCREB), (2) increased activation of CREB as a treatment for neurodegenerative symptoms, and (3) a potential therapeutic drug for neurodegenerative diseases that can target CREB signaling. The results of the systematic review showed evidence that suggested …

Mechanical Understanding And Optimization Of Template Guided Core Needle Biopsy, Isaac Girgis

Honors Undergraduate Theses

Prostate cancer is the second highest cause of cancer related deaths among men. According to the diagnostic pathway for prostate cancer, a prostate biopsy is performed if an individual showed signs of lesions through high prostate-specific antigen (PSA) concentration or suggestive digital rectal exam (DRE) results. The core biopsy mechanism involves inserting a beveled needle into the organ and removing a cylindrical fragment of tissue. Many factors affect the histological quality of the sample, including fragmentation, needle deflection, and needle insertion velocity. If a biopsy core is not clinically viable, an alternative core will need to be taken, resulting in …

Evaluation Of Interactions Of Covid Nonstructural Proteins 3, 5, And 6 With Human Proteins And Potentially Therapeutic Molecules, Jessica Huitsing

Honors Undergraduate Theses

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2, or SARS-CoV-2, has been ongoing for over two years. The virus spreads easily and is more unpredictable than well-known viruses like the flu, making it important to have reliable combative measures before we fully drop non-vaccine preventive actions, like mask-wearing.Therefore, we used computational protein modeling to investigate the interactions of three nonstructural proteins (abbreviated Nsp) encoded in the viral RNA genome– Nsp3, Nsp5, and Nsp6 – which are involved in the viral life cycle, with human P-type polyamine transporting ATPases ATP13A2 and ATP13A3, whose disease symptoms when mutated mimic …

Investigating The Relationship Between Biological Age And Mutant Huntingtin Misfolding, Ratnesh Kesineni

Honors Undergraduate Theses

Huntington Disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of a CAG trinucleotide repeat tract in the huntingtin (HTT) gene. This CAG tract expansion causes production of mutant HTT (mtHTT) protein, which misfolds and forms inclusions in the brain that accumulate with age. Misfolded mtHTT aggregates have been linked with increased cell death in neuron cell culture, leading to speculation that mtHTT aggregates cause cell death. However, there are mouse lines that have robust mtHTT inclusion deposition, but no HD-like signs or neurodegeneration. Furthermore, neuronal HD cultured cells with inclusions were found to be …

The Effect Of Young Blood Anti-Aging Treatment On Protein Markers Of Age And Huntington Disease, Sujena H. Koilpillai

Honors Undergraduate Theses

Huntington disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract within the huntingtin (HTT) protein, forming mutant HTT (mtHTT). HD patients suffer from psychiatric, behavioral, cognitive, and motor abnormalities, with death typically occurring 15-20 years after symptom onset. Currently, there are no treatments able to slow disease progression or delay onset. HD is a disease of aging. Despite the mtHTT protein being produced throughout life, symptoms do not typically appear until adulthood. Furthermore, many cellular effects of normal aging are also seen in HD, including altered intercellular communication and loss of proteostasis. Recently, our lab found …

Regulation Of The Protease Activity For The Mitochondrial Omi/Htra2, Simon Larson

Honors Undergraduate Theses

Human High Temperature requirement A2 (HtrA2) also known as Omi, is a serine protease located in the mitochondria with an important function in both cell survival and death. My results show the proteolytic activity of Omi/HtrA2 varies under different conditions. I characterized the optimal condition for Omi/HtrA2 protease activity using an in vitro assay system. Additionally, I identified a new allosteric regulation of Omi/HtrA2 through interaction with a specific substrate, the MUL1 protein. MUL1 is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with domains both inside mitochondria and in the cytoplasm. The data shown here strongly …

Automatic Posture Correction Utilizing Electrical Muscle Stimulation, Ravi Kiran Kattoju

Electronic Theses and Dissertations, 2020-

Habitually poor posture can lead to repetitive strain injuries that lower an individual's quality of life and productivity. Slouching over computer screens and smart phones, asymmetric weight distribution due to uneven leg loading, and improper loading posture are some of the common examples that lead to postural problems and health ramifications. To help cultivate good postural habits, researchers have proposed slouching, balance, and improper loading posture detection systems that alert users through traditional visual, auditory or vibro-tactile feedbacks when posture requires attention. However, such notifications are disruptive and can be easily ignored. We address these issues with a new physiological …

Development Of An Hipsc-Cortical Neuron Long-Term Potentiation Model And Its Application To Alzheimer's Disease Modeling And Drug Evaluation, Kaveena Autar

Electronic Theses and Dissertations, 2020-

Alzheimer's disease (AD) is commonly characterized by a loss of cognitive function due to the deterioration of neuronal synapses from the presence of senile amyloid beta-42 (Aß42) plaques. Evaluating cognitive deficits caused by Aß42 using human cortical neurons poses a challenge due to sourcing difficulties, and the use of animal models to assess drug efficacy creates biological hurdles from lack of species translatability. Recent advances in induced-pluripotent stem cell technology have enabled the development of mature, human-based cortical neuron models. The development of an hiPSC-cortical neuron differentiation protocol facilitates the exploration of disease onset and functional analysis from a patient-derived …

Investigating The Relationship Between The Microbiome And Neuroactive Metabolites In Huntington Disease Model Mice, Christian Millot

Electronic Theses and Dissertations, 2020-

Huntington Disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide repeat expansion mutation in the huntingtin (HTT) gene. HD is characterized by neurological symptoms, including motor, cognitive, and psychiatric decline. A non-neurological symptom, metabolic dysfunction, is also common in HD and can cause weight change, a feature recapitulated in HD mice. There is a need for a better understanding of the weight changes associated with HD, because patients with a higher body mass index show slower disease progression. Our lab has shown that metabolic dysfunction in HD mice is the result of a disrupted circadian feeding rhythm …

Downregulation Of Mir-34a Via Calorie Restriction Regulates Lipid Metabolism In The Liver Of Long-Living Ames Dwarf Mice, Sarah Ashiqueali

Electronic Theses and Dissertations, 2020-

Ames dwarf mice (df/df) display delayed aging relative to their normal siblings, living approximately 40-60% longer. As such, investigating the mechanisms that enable these organisms to have superior life expectancies may prove useful in developing therapies to slow aging and deter age-related disease. Nonalcoholic fatty liver disease (NAFLD) is a condition that is characterized by the accumulation of excess adipose tissue in the liver. Interestingly, its prevalence tends to increase with age with an incidence rate of greater than 40% in individuals over the age of 60. Previous studies highlight the potential of calorie restriction (CR) in promoting longevity, but …

Anti-Map Triple Therapy Supports Immunomodulatory Therapeutic Response In Crohn's Disease Through Downregulation Of Nf-Kb Activation In The Absence Of Map Detection, Erij Elkamel

Electronic Theses and Dissertations, 2020-

The triple antibiotic formulation, known as anti-MAP therapy, exhibits unique synergistic antimicrobial activity and should be effective for treatment of Crohn's disease (CD) associated with Mycobacterium avium subspecies paratuberculosis (MAP). The absence of MAP detection in some CD cases may be linked to poor diagnostics or lack of association with the disease. To understand the therapeutic response of some CD patients to anti-MAP therapy in absence of MAP detection, the immunomodulatory potency of anti-MAP therapy and its major ingredients, clarithromycin (CLA) and rifabutin (RIF), in THP-1, Caco-2, and Jurkat T-cells were investigated. Anti-MAP formulation at 2.0 µg/mL decreased MAP viability …

The Role Of Ms-818 In Altering Age-Related Characteristics Of An In Vitro Model Of Senescence In Neural Stem Cells, Sandeep Sreerama

Honors Undergraduate Theses

Aging of the brain is the leading risk factor for neurodegenerative diseases and brain cancers and has deleterious effects on brain functions. It follows that attempts to reverse the aging process may be therapeutically valuable. Neural stem cells (NSC) have been shown to play a critical role in maintaining brain functions, and their number is severely decreased with age. The development of senescence-like characteristics and declining functions in NSCs have been proposed to be responsible for brain aging and tumorigenesis. MS-818 is a pyrrolopyrimidine that has been shown to increase the NSC population and reverse the decline of behavioral function …

Developing A Targeted Ultrasound-Responsive Nanobubble-Based Gene Delivery System For Osteoporosis Treatment, Angela Shar

Honors Undergraduate Theses

The overall goal of this project was to develop, optimize, and test an ultrasound-responsive targeted nanobubble for delivering osteoporosis-related silencing genes such as Cathepsin K small interfering RNA (CTSK siRNA) for osteoporosis treatment. The nanobubbles were synthesized using an in situ sonochemical method. The nanobubble (NB) is composed of a gas core made from perfluorocarbon, stabilized with albumin, encapsulated with CTSK siRNA, and embedded with alendronate (AL) for bone targeting (CTSK siRNA-NB-AL). Following its development, the responsiveness of CTSK siRNA-NB-AL to a therapeutic ultrasound probe was examined. The results of biocompatibility tests with human bone marrow-derived mesenchymal stem cells proved …

Single Cell Forensic Genomics - Dna Profiling Of Micromanipulated Single Spermatozoa, Haley Hardin

Electronic Theses and Dissertations, 2020-

Current U.S. National guidelines allow for the collection of sexual assault evidence up to 5 days after the incidence occurs. In these cases, the ability to obtain an autosomal STR (aSTR) profile of the male donor in these cases diminishes as the time interval increases. This inability to recover an aSTR profile from the semen donor is not due to a complete lack of sperm cells, as studies have frequently shown that sperm persists in the vaginal canal or cervix up to 10 days post coitus. Thus, the inability to recover an aSTR profile of the sperm donor is likely …

Detection Of A Peptide Hormone - Somatostatin - Label-Free Split-Aptameric Probes, Charles A. Dowis

Honors Undergraduate Theses

Peptide hormones are important biomolecules that transduce downstream effects such as cell proliferation, regulation, and gene expression. Their levels have been upregulated in various disorders such as cancer, yet detection methods are lacking. We designed two split aptamer-based assays for the detection of a peptide hormone – Somatostatin (SST) – with different signal readouts: fluorescent readout based on light-up aptamers and the colorimetric readout of ABTS peroxidation from a G-quadruplex. We used an already selected split-aptamer –SSTA5–for SST for our designs and we had expected the developed detection systems to exhibit detection and quantification capabilities that would hopefully allow their …

Copper/N-Acetylcysteine Coated Iron Oxide Nanoparticles Synthesis, Characterization, And Antimicrobial Activities, Danya Belnour

Electronic Theses and Dissertations, 2020-

In recent years, there is a growing interest in developing metal based antimicrobial nanomaterials suitable for agricultural and biomedical applications. For centuries, Copper (Cu) biocide has been used for protecting a wide variety of crops from devastating bacterial and fungal diseases. However, prolonged and aggressive use of Cu led to the development of resistance and accumulation in soil. The latter has been linked to aquatic toxicity due to soil Cu leaching. Furthermore, copper build up in soil causes phytotoxicity and reduces uptake of micronutrient Zn through the root system. In biomedical field, Cu has been historically used as an antimicrobial …

Gelsolin-Mediated Actin Filament Severing In Crowded Environments, James Heidings

Electronic Theses and Dissertations, 2020-

Actin is an essential cytoskeletal protein that plays key roles in several cellular functions such as phagocytosis and cell motility with the help of actin binding proteins (ABPs). Gelsolin is a calcium regulated ABP that severs and caps actin filaments. Gelsolin helps control actin filament assembly dynamics that are required for cell survival. Cleavage products of gelsolin lead to Familial Amyloidosis, Finnish type, and conformational changes to gelsolin are implicated in disease progression. The majority of in vitro studies of gelsolin and actin have been performed in dilute buffer conditions which do not simulate the molecular interactions occurring in the …

Monitoring Pathological Gene Expression And Studying Endogenous Epigenetic Architecture By Crispr/Cas9-Based Tool Development Using Alpha-Synuclein As A Model, Levi Adams

Electronic Theses and Dissertations, 2020-

Until recently, complete understanding of the endogenous activity of pathologically relevant genes was out of reach and research was confined to in situ work, plasmid-based constructs and artificial model systems. The development and expansion of the CRISPR/Cas9 genome editing technique has enabled us to explore the molecular underpinnings of gene activation using the cell's own endogenous regulatory environment. In this work, we report on the development of a novel tool to monitor the endogenous activity of a causative gene in Parkinson's disease, a-synuclein. We use CRISPR/Cas9 to insert a highly sensitive engineered luciferase at the C-terminal of a-synuclein and assessed …

Nanopore-Based Metagenomic Comparison Of Airway Colonizers Between Cystic Fibrosis Patients And Healthy Individuals, Anita Samadabadi

Honors Undergraduate Theses

Cystic fibrosis (CF) is an autosomal recessive genetic disorder involving a mutation in the CF transmembrane conductance regulator protein (CFTR), which causes dysfunctional transport of chloride ions across cell membranes. CF affects multiple body systems and a few of its symptoms include chronic cough, difficulty breathing, obstructive airway disease, bacterial pulmonary infections, maldigestion, malabsorption, pancreatitis, and male infertility. Until recently, treatment options have been limited to alleviating symptoms, but a new classification of drugs, CFTR modulators, provide an opportunity to slow the progression of the disease and improve clinical outcomes. The effect of CFTR modulators may be attributed to the …

Systematic Literature Review Of Cognitive Behavioral Treatments For Patients With Classical, Secondary, And Idiopathic Trigeminal Neuralgia, Linnea B. Herzog

Honors Undergraduate Theses

Trigeminal neuralgia is a painful neuralgia with a complicated pathology that is not clearly understood. Due to the ambiguity of the condition, patients often have to search for medical providers that specialize in trigeminal neuralgia, and even with the guidance of a specialist, some patients do not respond well to treatment.¹ Despite the uncertainty surrounding the specifics of the disease, there are treatments available that can provide some level of pain relief for patients suffering from this disorder. When a patient does not respond well to medical therapy, surgery can be the next appropriate step in patient care management. …

Motor And Sensory Characterization Of A Mouse Model Of Charcot-Marie-Tooth Type 2o Disease, Swaran Nandini

Electronic Theses and Dissertations

Dynein is an essential motor protein required for the maintenance and survival of cells. Dynein forms a motor complex to carry intracellular cargoes like organelles, growth factors, peptides, and hormones along the microtubules inside the cells. In neurons, the dynein is the retrograde motor protein that moves cargoes from the neuronal tip to the neuronal soma along the length of an axon. Dynein has an established role in neuronal nuclear migration, transport of neuronal survival signals and growth factors, organelle positioning inside neurons etc. Hence, it is not very surprising that numerous mutations in dynein have been reported in association …

Ab Toxins: Recovery From Intoxication And Relative Potencies, Patrick Cherubin

Electronic Theses and Dissertations

AB-type protein toxins have a catalytic A subunit attached to a cell-binding B subunit. Ricin, Shiga toxin (Stx), exotoxin A, and diphtheria toxin are AB toxins that act within the host cytosol and kill the host cell through pathways involving the inhibition of protein synthesis. Our overall goal is to help elucidate the cellular basis of intoxication for therapeutic development. According to the current model of intoxication, the effect of AB toxins is irreversible. To test this model, we developed a system that uses flow cytometry and a fluorescent reporter to examine the cellular potency of toxins that inhibit protein …

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 …

Overview Of Direct Thrombin Inhibitors For Use In Staphylococcus Aereus Infections, Joseph C. Risler

Honors Undergraduate Theses

The pathogenicity and intractable nature of the microorganism Staphylococcus aureus (SA) has been long documented and highlighted by many health care agencies, with emphasis on its ability to exploit the human coagulation system to deadly effect. Two drugs from a class of inhibitors known as Direct Thrombin Inhibitors (DTI) have been shown to have a substantial effect on the enzyme secreted by SA known as Staphylocoagulase (SC), but up until now the application of this potential treatment has been limited. This paper strives to supply an overview of these clinical studies and propose a novel protocol for testing DTI's on …

Long-Term Outcomes Of Neonatal Herpes Simplex Virus Infection And Treatment, Genesis M. Brador

Honors Undergraduate Theses

The prevalence of herpes simplex virus (HSV) infection globally is high, and although there is no cure for it, the antiviral drug acyclovir is used to alleviate symptoms. There are two types of HSV: HSV-1, which typically infects the oral area, and HSV-2, which is associated with genital infections. A mother who carries the infection may transmit it to a neonate in different ways, most commonly via vaginal delivery in the presence of active lesions. There are three types of HSV disease that affect newborns: skin, eyes or mouth (SEM) disease, central nervous system (CNS) disease, or disseminated disease. The …

Impact Of Work-Life Balance On Health-Related Quality Of Life Among College Students, Emily Vernet

Honors Undergraduate Theses

Work-life balance involves the management of work and social responsibilities. Specifically, it describes the ability to meet the demands of multiple roles involving academics, social, personal, and professional life. Literature has shown that there is an increasing number of students who are working while taking classes at a university. Previous research has described how young adults balance working and going to school and how work hours influence student's mental, physical, and health behaviors. The purpose of this study is to examine the association between a student's ability to balance work demands, student and life responsibilities, and health outcomes. Using a …

It Takes Two To Tango: The Toxin-Chaperone Relationship, Alisha Kellner

Electronic Theses and Dissertations

Cholera toxin (CT) enters the cell via receptor-mediated endocytosis and travels in a retrograde fashion to the endoplasmic reticulum (ER). The catalytic A1 subunit (CTA1) is then displaced from the rest of the holotoxin, unfolds, and is exported to the cytosol where it regains an active conformation for the ADP-ribosylation of its G-protein target. We have shown that the cytosolic chaperones Hsp90 and Hsc70 are required for CTA1 translocation to the cytosol. We have also shown that both are able to independently bind and refold CTA1. Using libraries of CTA1-derived peptides, we have identified a single Hsc70 binding site, YYIYVI …