Disease Modeling Commons^™

Determinants Of Hypertension Awareness And Control In Kenya: A Secondary Analysis Of National Survey Data, Alexander K. Davis

Poster Presentations

No abstract provided.

Oral Pathogens Reprogram Endothelial Barrier And Angiotensin-Converting Enzyme2/Endothelial Nitric Oxide Synthase-Nitric Oxide Signaling To Promote Blood Pressure Dysregulation, Ming-Shou Hsieh, Tung-Nien Hsu, Chin-Sheng Huang, Ting-Yi Renn, Kuang-Tai Kuo, Kuo-Yao Lin, Wei Jen Chang

Journal of Dental Sciences

Background/purpose: Although periodontal disease is associated with an increased risk of hypertension, the endothelial mechanisms linking oral inflammation to vascular dysfunction remain unclear. We investigated whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) can directly disturb endothelial homeostasis and whether macrophage–endothelial crosstalk further worsens endothelial injury.

Materials and methods: Human umbilical vein endothelial cells (HUVECs) were exposed to Pg-LPS alone or co-cultured (transwell system) with Pg-LPS-primed human monocytic cells -derived macrophages. Endothelial dysfunction was assessed through nitric oxide (NO) production, endothelial nitric oxide synthase (eNOS) phosphorylation, inflammatory and adhesion molecule expression, as well as junctional and cytoskeletal changes. Macrophage …

Arrhythmogenic Right Ventricular Cardiomyopathy: A Comprehensive Review, Taha Shaikh, Darren Nguyen, Jasmine Dugal, Michael Dicaro, Brianna Yee, Nazanin Houshmand, Kachon Lei, Ali Namazi

Department of Internal Medicine Faculty Research

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by structural abnormalities, arrhythmias, and a spectrum of genetic and clinical manifestations. Clinically, ARVC is structurally distinguished by right ventricular dilation due to increased adiposity and fibrosis in the ventricular walls, and it manifests as cardiac arrhythmias ranging from non-sustained ventricular tachycardia to sudden cardiac death. Its prevalence has been estimated to range from 1 in every 1000 to 5000 people, with its large range being attributed to the variability in genetic penetrance from asymptomatic to significant burden. It is even suggested that the prevalence is underestimated, as the presence of genotypic mutations …

Blunt Cerebrovascular Injury (Bcvi): Universal Cta Neck Screening At Level 2 Trauma Center, Tamine Gogel

Doctor of Nursing Practice Projects

Blunt Cerebrovascular Injury (BCVI) refers to injuries to the vessels supplying blood to the brain, primarily carotid and vertebral arteries, and can result from trauma, resulting in stroke by vessel dissection, thrombus formation, embolization, and hemorrhage. Timely identification is crucial for effective intervention and improved outcomes. This doctoral project proposes the implementation of universal screening using Computed Tomography Angiography (CTA) of the neck during initial workup for blunt force trauma at a Level II ACS-verified trauma center. The primary objective is to mitigate potential delays in diagnosing and treating BCVI, thereby reducing the likelihood of complications. Patients ≥ 15 years …

The Effects Of Circadian Misalignment On Astrocyte Morphology In The Nucleus Tractus Solitarius, Kush C. Patel, Mina Shenouda, Diana Martinez

Rowan-Virtua Research Day

Circadian misalignment, as experienced by shift workers, was found to increase the number of astrocytes in the nucleus tractus solitarius (nTS) - a brain region crucial for autonomic control of blood pressure. Sprague Dawley rats subjected to a 6-hour light-dark phase delay every 2 days to simulate shift work exhibited a significant increase in astrocyte cell bodies compared to control rats, both at 9am and 9pm timepoints. The increase in astrocytes may lead to greater glutamate uptake, reducing extracellular glutamate levels in the nTS. Decreased glutamatergic neurotransmission in this region has been linked to the development of hypertension. These findings …

Code For Care: Hypertension Prediction In Women Aged 18-39 Years, Kruti Sheth

Electronic Theses, Projects, and Dissertations

The longstanding prevalence of hypertension, often undiagnosed, poses significant risks of severe chronic and cardiovascular complications if left untreated. This study investigated the causes and underlying risks of hypertension in females aged between 18-39 years. The research questions were: (Q1.) What factors affect the occurrence of hypertension in females aged 18-39 years? (Q2.) What machine learning algorithms are suited for effectively predicting hypertension? (Q3.) How can SHAP values be leveraged to analyze the factors from model outputs? The findings are: (Q1.) Performing Feature selection using binary classification Logistic regression algorithm reveals an array of 30 most influential factors at an …

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …

Sex Dimorphisms Of Aldosterone And High Salt Induced Aortic Aneurysms In Mice, Xufang Mu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aortic aneurysms, a permanent enlargement in the aorta, is a devastating disease with a high mortality rate after rupture. Aortic aneurysms exhibit strong sex dimorphisms: men are at higher risk than women while women experience worse outcomes if diagnosed. Currently, the only intervention is by open surgery or endovascular repair, and no drugs are approved for blunting the disease progression. This highlights the needs for mechanistic studies for sex-specific therapeutic targets.

Our lab established the mouse model in which mineralocorticoid receptor (MR) agonist aldosterone induces aortic aneurysms in the presence of high salt in male mice age-dependently, mimicking the aging …

Heart Disease Prediction Using Stacking Model With Balancing Techniques And Dimensionality Reduction, Ayesha Noor, Nadeem Javaid, Nabil Alrajeh, Babar Mansoor, Ali Khaqan, Safdar Hussain Bouk

School of Cybersecurity Faculty Publications

Heart disease is a serious worldwide health issue with wide-reaching effects. Since heart disease is one of the leading causes of mortality worldwide, early detection is crucial. Emerging technologies like Machine Learning (ML) are currently being actively used by the biomedical, healthcare, and health prediction industries. PaRSEL, a new stacking model is proposed in this research, that combines four classifiers, Passive Aggressive Classifier (PAC), Ridge Classifier (RC), Stochastic Gradient Descent Classifier (SGDC), and eXtreme Gradient Boosting (XGBoost), at the base layer, and LogitBoost is deployed for the final predictions at the meta layer. The imbalanced and irrelevant features in the …

A Machine Learning Approach For Early Diagnosis Of Transthyretin Amyloid Cardiomyopathy Among Heart Failure Patients, Tanjim Ahmed

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, progressive, and fatal disease. Prevalence of ATTR-CM ranges from 4 to 17 per 100000 cases where the mean survival time is less than 4 years. It has a history of being underdiagnosed and misdiagnosed. The diagnosis delay has a weighted mean of 6.1 years for wild-type ATTR-CM. Low awareness, the necessity of invasive procedures, and lack of treatment are the key reasons for delayed diagnosis. But, with the introduction of non-invasive tests like nuclear scintigraphy with ^99mTC-PYP and the disease modifying drug Tafamidis, the diagnosis delay signifies a missed opportunity to increase …

Building An Artificial Intelligence Framework For Hypertension Diagnosis: A Use Case Of The Problem List Curation, Ketemwabi Yves Shamavu

Theses & Dissertations

Hypertension is the world's leading factor in cardiovascular disease. Forty-seven percent or close to one in two Americans aged 18 and older are affected. It predicts approximately a thousand deaths per day. Based on recent statistics from the Centers for Disease Control and Prevention, one in three patients with hypertension does not know they are hypertensive. Seventy-five percent of hypertensive patients have uncontrolled hypertension - meaning that they are not treated to target. While there is extensive literature on hypertension diagnosis and management, there is an apparent gap in understanding and acknowledging that a person is hypertensive. Moreover, blood pressure …

Alternate Site Pacing And The Impact On Intracellular Calcium Handling During The Post-Extrasystolic Cardiac Cycle, Kent Ozcan, Lawrence Mulligan

Rowan-Virtua Research Day

Objective: Previous work has shown that alternate site (RV apex) results in myocardial dysfunction. With the development of tools to place endocardial pacing leads in locations that create physiological pacing activation, we sought to evaluate how ventricular trans-septal or left ventricular apical placement pacing differs from right atrial pacing. We will evaluate how these chronic pacing modes impact the PR and RF at baseline, 0, and 16 weeks in the canine heart.

Methods: Quantitative analysis will be performed on previously generated data. The data set includes pacing of 15 dogs total (8 with trans-septal leads & 7 with left ventricular …

Coronary Artery Disease: An Analysis Of Its Biochemical, Physiological, And Sociological Causes And Effects, Alexander Velazquez

Honors Theses

Coronary Artery Disease (CAD) is a serious condition caused by a buildup of plaque in your coronary arteries, the blood vessels that bring oxygen-rich blood to your heart. It disproportionately affects millions of Americans and thousands of Mississippians. This study presents the results of an evaluation of causation factors of CAD, the physiological impact on the body, and the contributing determinants of CAD on Mississippi populations. Data on Mississippi populations were collected using the Center for Population Studies at the University of Mississippi. A multitude of individuals were evaluated when examining the causes and effects of CAD including men, women, …

The Impact Of Prolonged Estrogen Deficiency On Cardiac Hypertrophy Following Chronic Sympathetic Stimulation, Isabelle Krueger

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of death for both men and women in developed countries. Compared to age-matched males, premenopausal women experience lower rates of CVD but this increases after menopause. A central feature in CVD is changes in sympathetic regulation leading to pathological changes such as cardiac hypertrophy characterized by changes in cardiomyocyte size due to overcompensation of the muscle following injury. The goal of this research is to study the effect of prolonged estrogen loss on cardiac hypertrophy following chronic sympathetic stimulation. Female mice were ovariectomized at 10 weeks of age and treated with Isoproterenol to …

Examination Of Strain-Dependent Differences In S. Sanguinis Virulence And Growth, Shannon Baker

Theses and Dissertations

Streptococcus sanguinis, an abundant and benign inhabitant of the oral cavity, is an important etiologic agent of infective endocarditis, particularly in people with pre-disposing cardiac valvular damage. Although commonly isolated from patients with IE, little is known about the factors that make any particular S. sanguinis isolate more virulent than another or, indeed, whether significant differences in virulence exist among isolates. To investigate the virulence of multiple isolates, a variation of the Bar-seq (barcode sequencing) method was employed. A conserved chromosomal site was identified for subsequent insertion of a barcode identifier, unique for each strain. Barcode insertion did not …

Modeling In The Physiology Classroom, Sowmya Anjur

Faculty Publications & Research

Physiology and Disease is a Biology elective at IMSA that has been developed to be mostly student-centered. Some examples of student projects include modeling heart structure to reflect function and creating LED arduino monitors to measure heart rate. Students also measure their lung capacity and blood pressure to demonstrate correlation of these values with heart rate, and trace the correlation back to neuronal controls. Projects such as these integrate other disciplines such as engineering and conform to NGSS Science and Engineering standards and NGSS Cross cutting Concepts standards. Students take responsibility for their own learning and articulate better on tests.

In Vitro Aortic Arch Flow Model For Vector Flow Imaging Testing, Jackson Mosley

Biomedical Engineering Undergraduate Honors Theses

Pediatric stenosis is the narrowing of the aorta at the aortic valve, above the aortic valve, or below the aortic valve. Typically, this disease’s severity is diagnosed by conventional Doppler ultrasound methods, or echocardiography. Conventional Doppler can sometimes overestimate the pressure gradient over the area of stenosis, diagnosing some cases of PAS to be more severe than they actually are. This causes earlier intervention than is desired in children. A new US modality, Vector Flow Imaging (VFI), is an angle-independent US imaging method that can potentially more accurately quantify peak blood flow velocities and pressure gradients across stenotic sections of …

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …

A Mixed-Methods Study: Self-Efficacy And Barriers To Participation In Workplace Wellness Programs, Massiel Perez-Calhoon

Dissertations

America needs a healthy workforce to sustain the country. The scourge of obesity continues to plague Americans despite government initiatives such as the Affordable Care Act and wellness programs in the workplace to combat this epidemic. However, despite initiatives to make America healthy, barriers continued to impede the nation’s health. Lack of awareness and sensitivity to what motivates individual participants versus group participants built formidable barriers to accessing all workplace employees equitably. The purpose of this study was twofold. First, the intent of this study was to explore the relationship between self-efficacy and the impact on participation and engagement when …

Orthogonal Decomposition Of Left Ventricular Remodeling In Myocardial Infarction, Xingyu Zhang, Pau Medrano-Gracia, Bharath Ambale-Venkatesh, David A. Bluemke, Brett R. Cowan, J. Paul Finn, Alan H. Kadish

Office of the President Publications and Research

BACKGROUND: Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices.

RESULTS: Six clinical remodeling indices (end-diastolic volume index, sphericity, relative wall thickness, ejection fraction, apical conicity, and longitudinal shortening) were evaluated using cardiac magnetic resonance images of 300 patients with myocardial infarction, and 1991 asymptomatic subjects, obtained from …

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Using Mathematical Modeling To Unmask The Concealed Nature Of Long Qt-3 Syndrome, Steven Poelzing, Amara Greer-Short, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Low Energy Defibrillation By Synchronization; 90 % Less Energy Compared To One Shock., Flavio H. Fenton, Yanyan Ji, Ilija Uzelac, Niels Otani, Elizabeth M. Cherry

Biology and Medicine Through Mathematics Conference

No abstract provided.

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations and Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

Information Maximizing Component Analysis Of Left Ventricular Remodeling Due To Myocardial Infarction, Xingyu Zhang, Bharath Ambale-Venkatesh, David A. Bluemke, Brett R. Cowan, J. Paul Finn, Alan H. Kadish, Pau Medrano-Gracia

Office of the President Publications and Research

Background: Although adverse left ventricular shape changes (remodeling) after myocardial infarction (MI) are predictive of morbidity and mortality, current clinical assessment is limited to simple mass and volume measures, or dimension ratios such as length to width ratio. We hypothesized that information maximizing component analysis (IMCA), a supervised feature extraction method, can provide more efficient and sensitive indices of overall remodeling.

Methods: IMCA was compared to linear discriminant analysis (LDA), both supervised methods, to extract the most discriminatory global shape changes associated with remodeling after MI. Finite element shape models from 300 patients with myocardial infarction from the …

The Role Of Angiotensinogen In Atherosclerosis And Obesity, Congqing Wu

Theses and Dissertations--Nutritional Sciences

Angiotensinogen is the only known precursor in the renin-angiotensin system, a hormonal system best known as an essential regulator of blood pressure and fluid homeostasis. Angiotensinogen is sequentially cleaved by renin and angiotensin- converting enzyme to generate angiotensin II. As the major effector peptide, angiotensin II mainly function through angiotensin type 1 receptor.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and more recently renin inhibitors are widely known as the 3 classic renin-angiotensin system inhibitory drugs against hypertension and atherosclerosis. Here, we developed an array of regents to explore the effects of angiotensinogen inhibition. First, we demonstrated that genetic deficiency of …

Atlas-Based Quantification Of Cardiac Remodeling Due To Myocardial Infarction, Xingyu Zhang, Brett R. Cowan, David A. Bluemke, J. Paul Finn, Carissa G. Fonseca, Alan H. Kadish, Pau Medrano-Gracia

Office of the President Publications and Research

Myocardial infarction leads to changes in the geometry (remodeling) of the left ventricle (LV) of the heart. The degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. In this paper, we present a novel analysis framework for characterizing remodeling after myocardial infarction, using LV shape descriptors derived from atlas-based shape models. Cardiac magnetic resonance images from 300 patients with myocardial infarction and 1991 asymptomatic volunteers were obtained from the Cardiac Atlas Project. Finite element models were customized to the spatio-temporal shape and function of each case using guide-point modeling. Principal component analysis …

Atlas-Based Analysis Of Cardiac Shape And Function: Correction Of Regional Shape Bias Due To Imaging Protocol For Population Studies, Pau Medrano-Gracia, Brett R. Cowan, David A. Bluemke, J. Paul Finn, Alan H. Kadish, Daniel C. Lee, Alistair A. Young

Office of the President Publications and Research

Background: Cardiovascular imaging studies generate a wealth of data which is typically used only for individual study endpoints. By pooling data from multiple sources, quantitative comparisons can be made of regional wall motion abnormalities between different cohorts, enabling reuse of valuable data. Atlas-based analysis provides precise quantification of shape and motion differences between disease groups and normal subjects. However, subtle shape differences may arise due to differences in imaging protocol between studies.

Methods: A mathematical model describing regional wall motion and shape was used to establish a coordinate system registered to the cardiac anatomy. The atlas was applied …

Hypoxia-Sensitive Gene Expression In The Gastrocnemius Muscle Following Chronic Hind Limb Ischemia, Andrew Tilton

Biological Sciences

Chronic ischemia, caused by the formation atherosclerotic plaque occlusions in major conduit arteries, is the leading cause of morbidity and mortality in western societies. Vascular remodeling can help compensate for the adverse effects of atherosclerotic plaque formation. Vascular remodeling relies heavily on vascular endothelial growth factor (VEGF), a critical protein that contributes to all forms of vascular formation and remodeling including angiogenesis, arteriogenesisand vasculogenesis. VEGF itself is up-regulated by the transcription factor, hypoxia inducible factor 1 alpha (HIF-1α), which becomes activated in low oxygen environments.

Through the use of animal chronic hindlimb ischemia models, these genes can be evaluated as …

Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers

Master's Theses

Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.