Medical Sciences Commons^™

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

Investigation Of Macrod2 As A Biomarker Of Treatment Resistance In Human Papillomavirus-Related Head And Neck Cancer, Alice Anne Dawson

Electronic Thesis and Dissertation Repository

Head and neck squamous cell carcinoma (HNSCC) is the 6^th most common cancer worldwide. Infection by human papillomavirus (HPV) has caused a rise in HNSCC cases. Unfortunately, a cohort of HPV+ HNSCC patients exhibit treatment resistance. At present, no known treatment resistant biomarkers have been identified. We completed genomic characterization of a local HPV+ HNSCC cohort and observed MACROD2 deletions in the treatment failure dataset. Functional validation revealed siRNA and shRNA MACROD2 knockdown in HNSCC cells led to elevated cell viability and colony formation. Interestingly, shMACROD2 caused no change in cisplatin sensitivity, but a significant increase in radiation resistance …

Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro

Dissertations & Theses (Open Access)

DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …

Mechanisms Underlying Stem Cell Depletion In Ageing., Mackenzie Hsu

Electronic Thesis and Dissertation Repository

As we age, our bodies lose the ability to repair damaged tissues. This impairment may be due to age-related deficits in our regenerative stem cells. Stem cells reside in specialized areas called stem cell niches. Ageing may cause alterations in the stem cells directly or may alter the stem cell niche to generate deficits. However, systematic studies mapping stem cell deficits and alterations to stem cell niche are lacking. Here, I investigated the bone marrows of young and aged mice to determine age-related changes in the microenvironment that may alter resident stem cells.

To achieve my research objective, I examined …

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz

Theses and Dissertations

The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the Kras^G12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …

Diagnostic Accuracy Of High-Sensitivity Cardiac Troponin In The Diagnosis Of Acute Myocardial Infarction At The Aga Khan University Hospital Nairobi, Kenya, Assumpta Wanjiru Chege

Theses & Dissertations

Methodology: This cross-sectional study was carried out at Aga Khan University Hospital, Nairobi between July 1st 2020 and December 31st 2021. Participants were adults aged 18 years and above presenting to the emergency department with signs and symptoms suggesting an acute myocardial infarction. Patients were identified on the hospital management information system (CARE 2000) using test results for baseline high-sensitivity cardiac troponin I. The final diagnosis as well as secondary clinical data was obtained from both physical and electronic patient medical records. The reference standard for the diagnosis of acute myocardial infarction was taken as the final clinical diagnosis made …

Perioperative Risks Of The Patient With Heart Failure, Gabrielle Metoyer

Nursing Student Class Projects (Formerly MSN)

Perioperative Risks of the Patient with Heart Failure

Gabrielle Metoyer

Department of Nursing, Otterbein University

NURS 6810 – Advanced Pathophysiology

Dr. Deanna Batross and Dr. Shivani Bhatnagar

August 5, 2022

Abstract

According to the CDC (2020), heart failure occurs when the heart cannot pump enough blood and oxygen to support other organs in your body. Heart failure is an epidemic disease affecting 1-2% of the population worldwide (Schwinger, 2020). It is one of the leading causes of morbidity and mortality worldwide with an estimated 6.5 million adults with heart failure in the United States (Lo et al., 2021). Medical advances …

Anthracyclines Attenuate The Nrf1-Mediated Bounce-Back Response, Bader Albalawi

Theses and Dissertations

Proteasome inhibitors, such as carfilzomib, are FDA-approved to treat multiple myeloma and mantle cell lymphoma. Unfortunately, proteasome inhibitors have only produced clinically significant results in patients with hematologic cancers, despite their predicted pan-cancer utility, and even hematologic cancer types frequently show intrinsic and acquired resistance.

One proposed mechanism responsible for the proteasome inhibitors' shortcomings is the NRF1-mediated bounce-back response. Identification of drugs that can potentiate the action of proteasome inhibitors could overcome resistance in patients with hematologic cancers and expand proteasome inhibitors' use to treat solid tumors. Our previous studies have identified anthracyclines as potential compounds that interfere with the …

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …

Mechanisms Underlying Enhanced Bone Marrow Adipogenesis In Diabetes, Jina J.Y. Kum

Electronic Thesis and Dissertation Repository

Morbidity and mortality associated with diabetes are due to secondary vascular complications that include both micro- and macro-vascular organ dysfunctions. Our recent studies show that vascular dysfunction and inadequate vessel repair in diabetes may potentially be due to impaired vasculogenesis (de novo vessel formation). Specifically, we have shown that diabetes enhances adipogenesis in the bone marrow and reduces the number of marrow-resident vascular regenerative stem cells. In this study, I have determined the mechanisms of deleterious bone marrow adipogenesis, which may alter the cellular composition of the marrow and lead to the depletion of vascular regenerative stem cells.

My …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

The Utility Of An Initial Point-Of-Care Lactate In Predicting In-Hospital Mortality Among Adult Patients With Sepsis And Septic Shock At The Emergency Department Of A Tertiary Hospital In Nairobi, Gicheru B. Nyachira

Theses & Dissertations

Background: Sepsis is a leading cause of death and now a global health priority. Rapid identification, diagnosis and intervention can result in reduced in-hospital mortality. Elevated lactate has been shown to be a strong predictor of in-hospital mortality. However, the optimal cut-off has not been well defined. Identification of the optimal Point-of-Care (POC) lactate cut off that best predicts in-hospital mortality can therefore be used to rapidly risk stratify patients with suspected sepsis and septic shock presenting to the emergency department allowing for immediate intervention.

Objective: To determine the lactate cutoff from an initial Point-of-Care lactate result from a GEM …

Imaging Based Prediction Of Pathology In Adult Diffuse Glioma With Applications To Therapy And Prognosis, Evan Gates

Dissertations & Theses (Open Access)

The overall aggressiveness of a glioma is measured by histologic and molecular analysis of tissue samples. However, the well-known spatial heterogeneity in gliomas limits the ability for clinicians to use that information to make spatially specific treatment decisions. Magnetic resonance imaging (MRI) visualizes and assesses the tumor. But, the exact degree to which MRI correlates with the actual underlying tissue characteristics is not known.

In this work, we derive quantitative relationships between imaging and underlying pathology. These relations increase the value of MRI by allowing it to be a better surrogate for underlying pathology and they allow evaluation of the …

Trna Regulation In Humans: The Cellular Effect Of A Pathological Hars Y454s Mutation, Rosan Kenana

Electronic Thesis and Dissertation Repository

tRNAs are the adapter molecules involved in translating the genetic code into functional protein in a living cell. tRNAs are charged with their cognate amino acids - by aminoacyl-tRNA synthetases (aaRS or ARS) - which are then transferred to a growing peptide in a process called mRNA translation. The efficiency of translation is dependent on the ratio of ARS enzymes to their cognate tRNAs and the availability of correctly amino acylated tRNAs. Disruptions of this process, caused by mutations in ARS genes, in particular, have been linked to complex inherited diseases. USH3B syndrome, a recessively inherited disorder among consanguineous families …

Novel Imaging Tools Reveal The Dynamics Of The Myocardial Growth Hormone Secretagogue Receptor In Heart Disease And Heart Failure, Rebecca Sullivan

Electronic Thesis and Dissertation Repository

Heart disease (HD) is the leading cause of mortality worldwide. Currently, diagnosis is based on clinical features, imaging, and circulating cardiac biomarkers. Cardiac imaging technologies, such as echocardiography and cardiac magnetic resonance imaging (cMRI), enable the non-invasive detection of changes in heart function. Although these modalities can detect changes in structure and anatomy, it is usually at later stages, where prevention may not be possible. In conjunction with imaging, circulating biomarkers of heart failure (HF), notably B-type natriuretic peptide (BNP) and cardiac troponin I and T, can be detected with increased levels in the blood. These biomarkers are associated with …

Evaluating Soluble Axl As A Biomarker For Glioblastoma, Daniel Raymond

All NMU Master's Theses

AXL, a receptor tyrosine kinase, is known to promote malignant phenotypes in various types of cancer. AXL overexpression is commonly observed in glioblastoma and correlates with a worse prognosis. Detectable in most biological fluids, the extracellular domain of AXL, sAXL, is the product of enzymatic cleavage by ADAM10/17. Here we used ELISA, BCA and BCG assays to characterize blood serum from 23 newly diagnosed GBM patients which was collected roughly 24 hours before and after surgery as well as every three months post-surgery, corresponding to follow-up treatment visits. Immunoblotting was used to determine relative AXL expression in 13 patient tumor …

Implications Of Long Non-Coding Rnas In The Pathogenesis Of Diabetic Retinopathy: A Novel Epigenetic Paradigm., Saumik Biswas

Electronic Thesis and Dissertation Repository

With the rising incidence of diabetic retinopathy (DR), there is an urgent need for novel therapies. Presently, several altered metabolic pathways have been implicated in the pathogenesis of DR. Recent advances in genomic technologies have identified considerable epigenetic alterations that also contribute to DR progression. Long non-coding RNAs (lncRNAs; >200 nucleotides), critical regulators of gene expression, are aberrantly expressed in DR and have not been comprehensively characterized. Our microarray analyses using human retinal endothelial cells (HRECs) revealed thousands of differentially expressed lncRNAs following high glucose (HG) exposure, with profound increases in the lncRNAs MALAT1 and HOTAIR. Using multiple techniques, …

Malignant Hyperthermia For The Nurse Anesthetist, Victor Clark

Nursing Student Class Projects (Formerly MSN)

Malignant Hyperthermia (MH) is a rare, autosomal dominant skeletal muscle disorder that can have an insidious onset in susceptible patients exposed to the triggering agents succinylcholine, halothane, desflurane, sevoflurane, and isoflurane. MH can occur in patients who have received anesthesia with these agents in the past (Nagelhout & Plaus, 2018, p 775). Patients with a family history of MH or associated skeletal muscle disorder must be treated as MH-susceptible until proven otherwise. Failure to detect an MH crisis can lead to kidney failure, profound acidosis, coagulopathies, rhabdomyolysis, cardiac dysrhythmias, cardiovascular collapse, and death (Seifert et al., 2015). It is the …

Fall Prevention Assessment In The Intermediate Care Patient Population, Dawn Rose

Doctor of Nursing Practice Final Manuscripts

Fall Prevention Assessment in the Intermediate Care Patient Population

Falls cause greater than 600,000 deaths per year and are the most common injury in people over 65 years of age. Fall prevention in the acute care setting has been identified as key goal in the most recent JCAHO review process. Falls on an intermediary care unit lead to an increased rate of morbidity, delayed discharge, and excess cost expenditure.

Even with appropriate evidence-based tools in place, Hospital A’s intermediate care unit, recorded an increased rate of falls; the highest rate in its health care system. An investigation identified factors contributing …

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

Investigating Medical Examiners' Practices: Genetic Evaluation For Fatal Acute Aortic Dissection, Bradley Power

Dissertations & Theses (Open Access)

Acute thoracic aortic dissection (TAD) is a life-threatening event with a hereditary component. Currently, pathogenic variants in 11 genes associated with aortic aneurysm and dissection predispose to a heritable form of disease thereby conferring an increased risk for TAD. Genetic testing plays a pivotal role not only in diagnosis, but also in risk stratification for relatives and medical management to prevent premature death from dissection. Due to its high fatality rate, medical examiners and coroners (ME/Cs) may be the first to identify TAD cases and initiate genetic testing for the decedent and at-risk relatives. ME/Cs were surveyed using three clinical …

Fomo, Liquid Courage, And The Intoxicated Self, Lindsay Pressman

Senior Theses and Projects

“Binge-drinking” cannot simply be recognized as a feature of campus culture, but as the product of a profoundly alienating one, made strikingly evident by our creation of a separate world (“drunk world”). We have created a small world of impossible possibles that exists in the corners of the actual; a separate world, in which the imagining of the self, other, and the world, is not only permissible but promoted. At the heart of college students’ “partying hard” is a longing, hope, and dogged determination that the liberating and unifying aspects of this world can overwhelm the actual...and in the meantime …

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.¹ Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Analyzing The Effects Of Opioids On Cortical Pore Networks In Rabbit Tibiae And Femora, Kassidy Wilson

Williams Honors College, Honors Research Projects

The following project was approved by the Institutional Animal Care and Use Committee (IACUC) (Protocol number #18-11-12 ARC). This study was completed as a subset of Dr. Andronowski's overarching lab project. Femora and tibiae were procured from New Zealand White rabbits to study the prolonged effects of opioid use in bone remodeling. This specific project analyzed the effects of opioids on the pore networks and the pore orientation.

Discovery Of Novel Mechanisms Regulating Cancer Extravasation In The Chorioallantoic Membrane Model, Yohan Kim

Electronic Thesis and Dissertation Repository

Cancer metastasis is a multistep process that begins with the invasion of tumour cells into the stroma and migration towards the blood vessels. Tumour cells that have entered the bloodstream must then survive and leave by a process known as extravasation. Finally, extravasated cells proliferate and establish the secondary site in the metastatic cascade. Although extravasation encompasses key events during cancer cell invasion to aid in the development of effective treatments, an in vivo model that rapidly, reproducibly and economically recapitulates cancer cell extravasation is needed. Therefore, the objectives of my research were to 1) establish and validate an in …

The Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer

Electronic Thesis and Dissertation Repository

Cytoplasmic inclusions and fibrils of the microtubule-associated protein tau (tau protein) are a key neuropathological hallmark in tauopathies, including Alzheimer’s disease, chronic traumatic encephalopathy, and amyotrophic lateral sclerosis with cognitive impairment. Previous research has demonstrated that the phosphorylation of tau protein at Thr¹⁷⁵ is sufficient for the initiation of fibril formation both in vitro and in vivo. Here we use mutated tau protein constructs to demonstrate that phosphorylation at Thr¹⁷⁵ results in the aberrant exposure of an N-terminal phosphatase-activating domain (PAD). The tau PAD interacts with protein phosphatase 1 (PP1) leading to the activation of glycogen synthase …

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found …

Agent Based Model Of Cavitation In Spinal Cord Injury, Rahma Ahmed

Senior Projects Spring 2019

Annually, approximately 375,000 people suffer from spinal cord injury (SCI) worldwide and many SCI patients develop secondary health conditions such as respiratory, cardiovascular, and urinary/bowel complications which negatively impact their daily lives. SCI occurs when there is damage to the spinal cord resulting in decreased motor functions, decreased sensory functions, or paralysis. Days to weeks after initial impact, the lesion (area of injury) continues to increase in size in a process called progressive cavitation which demyelinates axons and inhibits effective axonal regeneration. In an in vitro model of progressive cavitation, Fitch et al. showed that activated macrophages cause cavities to …