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Full-Text Articles in Diseases

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du May 2022

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du

Theses & Dissertations

The prevalence of nonalcoholic fatty liver disease (NAFLD) among Chinese young adults (CYA) aged 18-25 years ranges from 4.7% to 15.1% and has kept increasing in recent years. Previous studies reported limited awareness and knowledge of NALFD among middle-aged and older Chinese populations, however, they have not investigated awareness in CYA, for which there is no well-validated questionnaire. There is currently no efficacious educational intervention on NAFLD for CYA.

The objectives were 1) to develop and validate a questionnaire which can be used to assess the awareness and knowledge of NAFLD among CYA; 2) to assess the awareness and knowledge …


Building An Artificial Intelligence Framework For Hypertension Diagnosis: A Use Case Of The Problem List Curation, Ketemwabi Yves Shamavu May 2022

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 …


Frailty And Neurocognition In Prostate Cancer, Lindsey Hanson May 2022

Frailty And Neurocognition In Prostate Cancer, Lindsey Hanson

Theses & Dissertations

Prostate cancer (PCa) treatment often leads to distressing side effects ranging from muscle loss, physical inactivity, and fatigue to cancer associated cognitive decline (CACD). Evidence suggests that men treated with androgen deprivation therapy (ADT) may have a specifically high risk of CACD, partially due to increased frailty. However, the current literature on cognitive effects of ADT is equivocal. Therefore, the primary objectives of this study were to (1) compare cognitive function, physical activity (PA), and fitness in men receiving ADT, men scheduled to receive radiation, and men under active surveillance for PCa; (2) examine changes in cognitive performance and PA …


Fortuitous Diagnosis Of Total Anomalous Pulmonary Venous Return In A Newborn With Hypoglycemia, Joseph Maes, Terence Zach May 2022

Fortuitous Diagnosis Of Total Anomalous Pulmonary Venous Return In A Newborn With Hypoglycemia, Joseph Maes, Terence Zach

Child Health Research Institute Pediatric Research Forum

No abstract provided.


Interrogating Race And Place-Based Inequities In Hiv And Covid-19, Rohan Khazanchi Apr 2022

Interrogating Race And Place-Based Inequities In Hiv And Covid-19, Rohan Khazanchi

EMET Projects

Over the last four years, I have developed a research focus examining the intersections of race, place, and health. My M.D. Honors Thesis reflects a snapshot of these efforts. In this collection of brief research reports, I leverage area-based measures to investigate structural inequities in three contexts: the HIV epidemic in our hyperlocal community, the early stages of the COVID-19 pandemic, and clinical trials for novel COVID-19 therapeutics. I apply novel social epidemiologic tools to measure and explore disparate outcomes. And, in reflecting upon my findings, I discuss concrete implications for clinicians, researchers, and policymakers alike.

Chapter 1: Neighborhood-Level Deprivation …


Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth Jan 2022

Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

OBJECTIVE: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

METHODS: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples. Image registration and machine learning algorithms were developed to largely automate an imaging analysis pipeline identifying distinct cell …


Dually Active Polycation/Mirna Nanoparticles For The Treatment Of Fibrosis In Alcohol-Associated Liver Disease, Chuhan Zhang, Yu Hang, Weimin Tang, Diptesh Sil, Heather Jensen Smith, Robert G. Bennett, Benita L. Mcvicker, David Oupicky Jan 2022

Dually Active Polycation/Mirna Nanoparticles For The Treatment Of Fibrosis In Alcohol-Associated Liver Disease, Chuhan Zhang, Yu Hang, Weimin Tang, Diptesh Sil, Heather Jensen Smith, Robert G. Bennett, Benita L. Mcvicker, David Oupicky

Journal Articles: Eppley Institute

Alcohol-associated liver disease (AALD) is a major cause of liver disorders worldwide. Current treatment options are limited, especially for AALD-associated fibrosis. Promising approaches include RNA interference for miR-155 overexpression in Kupffer cells (KCs), as well as the use of CXCR4 antagonists that inhibit the activation of hepatic stellate cells (HSCs) through the CXCL12/CXCR4 axis. The development of dual-functioning nanoparticles for the effective delivery of antifibrotic RNA together with a CXCR4 inhibitor thus promises to improve the treatment of AALD fibrosis. In this study, cholesterol-modified polymeric CXCR4 inhibitor (Chol-PCX) was synthesized and used to encapsulate anti-miR-155 or non-coding (NC) miRNA in …


Modified Chitosan For Effective Renal Delivery Of Sirna To Treat Acute Kidney Injury., Weimin Tang, Chinmay M. Jogdeo, Sudipta Panja, Siyuan Tang, Ling Ding, Ao Yu, Kirk W. Foster, Del L. Dsouza, Yashpal S. Chhonker, Heather Jensen Smith, Hee-Seong Jang, Erika I. Boesen, Daryl J. Murry, Babu Padanilam, David Oupicky Jan 2022

Modified Chitosan For Effective Renal Delivery Of Sirna To Treat Acute Kidney Injury., Weimin Tang, Chinmay M. Jogdeo, Sudipta Panja, Siyuan Tang, Ling Ding, Ao Yu, Kirk W. Foster, Del L. Dsouza, Yashpal S. Chhonker, Heather Jensen Smith, Hee-Seong Jang, Erika I. Boesen, Daryl J. Murry, Babu Padanilam, David Oupicky

Journal Articles: Eppley Institute

Acute kidney injury (AKI) is characterized by a sudden decrease in renal function and impacts growing number of people worldwide. RNA interference (RNAi) showed potential to treat diseases with no or limited conventional therapies, including AKI. Suitable carriers are needed to protect and selectively deliver RNAi to target cells to fully explore this therapeutic modality. Here, we report on the synthesis of chitosan modified with α-cyclam-p-toluic acid (C-CS) as a novel siRNA carrier for targeted delivery to injured kidneys. We demonstrate that conjugation of the α-cyclam-p-toluic acid to chitosan imparts the C-CS polymer with targeting and antagonistic properties to cells …


Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan Jan 2022

Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Pulmonary & Critical Care Med

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.

Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.

Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on …


Retropharyngeal Abscess And Pott’S Disease Due To Tuberculosis: A Case Report, Bailey N. Hassman, Steven D. Curry, Jonathan H. Ryder, Angela L. Hewlett, Jayme R. Dowdall Dec 2021

Retropharyngeal Abscess And Pott’S Disease Due To Tuberculosis: A Case Report, Bailey N. Hassman, Steven D. Curry, Jonathan H. Ryder, Angela L. Hewlett, Jayme R. Dowdall

Graduate Medical Education Research Journal

Introduction: Extrapulmonary mycobacterial infection can lead to vertebral spondylitis and osteomyelitis (Pott’s disease). Retropharyngeal abscess with concurrent spinal osteomyelitis is a rare presentation of tuberculosis in the US. Chart review on a patient was completed, and the relevant published literature was reviewed.

Case Presentation: A previously healthy 34-year-old male originally from Sudan presented to an outside hospital with a 2-month history of neck pain, sore throat, odynophagia, fevers, and chills. MRI showed a retropharyngeal abscess and suspected cervical spine osteomyelitis. Acid-fast bacillus (AFB) smear was positive from a neck drain specimen, but sputum was negative. Chest imaging did not show …


Point Of Care Spirometry Assessment For Pediatric Asthma Prevalence In A Family Homeless Shelter In Omaha, Nebraska, Nathaniel Mattison, Dale Agner, Breanne Parets, Haley Mathews, Emily Saliga, Maria Vacha, Jamicah Harris, Ryan Saliga Dec 2021

Point Of Care Spirometry Assessment For Pediatric Asthma Prevalence In A Family Homeless Shelter In Omaha, Nebraska, Nathaniel Mattison, Dale Agner, Breanne Parets, Haley Mathews, Emily Saliga, Maria Vacha, Jamicah Harris, Ryan Saliga

Graduate Medical Education Research Journal

Abstract:

Introduction: The few studies on pediatric asthma in US homeless shelters describe a 27.9 – 39.8% prevalence, and historically Omaha has had a high incidence of fatal pediatric asthma. Thereby, Clarkson Family Medicine (CFM) residency began a pediatric asthma outreach to a local family-homeless shelter to assess the prevalence of pediatric asthma and follow-up appointment attendance.

Methods: We obtained a voluntary parent-child assessment of the child’s respiratory history and an Asthma Control Test (ACT) between ages 4-18 for children residing at the family-homeless shelter. We obtained a pre-albuterol and post-albuterol mobile spirometer assessment using the Global Initiative for …


Evaluation Of Stratified Antibiograms For Use In Laboratory And Antimicrobial Stewardship, Linsey Donner Dec 2021

Evaluation Of Stratified Antibiograms For Use In Laboratory And Antimicrobial Stewardship, Linsey Donner

Theses & Dissertations

Antibiograms are critical for choosing empiric antimicrobial therapy. Cumulative antibiograms, which aggregate susceptibility data, can mask differences within specific patient subsets or clinical syndromes. This dissertation was done to determine if antibiotic susceptibilities showed substantial differences when comparing stratified antibiograms to cumulative antibiograms.

Antibiotic susceptibility data was retrospectively obtained from Nebraska Medicine January 1, 2017 – December 31, 2019 for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The University of Nebraska Medical Center’s web antibiogram clinical decision support tool was used to export the data. Bacteria-antibiotic susceptibility rates of stratified antibiograms …


The Role Of Micrornas In The Pathophysiology Of Neonatal Hypoxic-Ischemic Brain Injury, Eric S. Peeples Dec 2021

The Role Of Micrornas In The Pathophysiology Of Neonatal Hypoxic-Ischemic Brain Injury, Eric S. Peeples

Theses & Dissertations

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. The subsequent metabolic failure and cellular injury in the brain can be partially attenuated by rapid initiation of therapeutic hypothermia, but even with prompt induction of hypothermia, more than one in four survivors suffer from major developmental disabilities – an indication of the critical need for more effective therapies. MicroRNAs (miRNA) may be able to act as therapeutic targets in neonatal HIBI; however, very little is known about the endogenous expression of miRNAs …


Humanized Mice For Brain Infection Of Emerging Viruses, Edward Makarov Dec 2021

Humanized Mice For Brain Infection Of Emerging Viruses, Edward Makarov

Theses & Dissertations

Studies on the pathogenesis of emerging viruses that present a global threat are critical for pathogen classification and therapeutic development. Humanized mice enable investigation of viral pathogens, including Human immunodeficiency virus (HIV-1), Zika virus (ZIKV), Coronavirus 2 (SARS-CoV-2), and Dengue virus (DENV), offering an advanced understanding into the mechanisms of viral perseverance in its natural human host cells and for therapeutic discovery. Realizing the diverse dynamics of various viral infections with the capacity to establish an innovative acuity for therapeutics and mechanics when utilizing humanized mice contributes a formerly inaccessible insight into human-specific viral pathogenesis and treatment. We recently developed …


Derivation And Validation Of A General Predictive Model For Long Term Risks For Mortality And Invasive Cardiovascular Interventions In Congenital Heart Disease, David A. Danford Dec 2021

Derivation And Validation Of A General Predictive Model For Long Term Risks For Mortality And Invasive Cardiovascular Interventions In Congenital Heart Disease, David A. Danford

Capstone Experience

Introduction. Accurate assessment of prognosis is a key driver of clinical decision making in congenital heart disease (CHD), but is complicated because CHD represents such a diverse collection of conditions. The aim of this investigation is to derive, validate, and calibrate multivariable predictive models for time to surgical or catheter-mediated intervention (INT) in CHD and for time to death in CHD. Methods. 4108 unique subjects were prospectively and consecutively enrolled, and randomized to derivation and validation cohorts. Total follow up was 26,578 patient-years, with 102 deaths and 868 INTs. Accelerated failure time multivariable predictive models for the outcomes, based on …


Mycobacterium Avium Pulmonary Infection Disguised As A Urinary Tract Infection, Megan Rolfzen, Allison Ashford Oct 2021

Mycobacterium Avium Pulmonary Infection Disguised As A Urinary Tract Infection, Megan Rolfzen, Allison Ashford

Graduate Medical Education Research Journal

In the United States, Mycobacterium avium complex (MAC) has been found to be the most common isolate in non-tuberculous disease, and pulmonary infection is the most frequent presentation. It is ubiquitous in the environment, particularly in soil and manufactured water supply sources. Worldwide, M. avium infections, both pulmonary and disseminated, are steadily increasing. Due to MAC’s ability to cause non-specific symptoms and its pervasiveness within the environment, it is paramount to incorporate this diagnosis in the differential, especially in those most susceptible. We report a case of a Mycobacterium avium complex pulmonary infection in 72-year-old Caucasian male with history of …


The Role Of Photography In Increasing Efficiency Of Dermatologic Inpatient Consulting Service, Ritu Swali, Tyler D. Evans, Dillon Clarey, Corey Georgesen, Ashley Wysong Oct 2021

The Role Of Photography In Increasing Efficiency Of Dermatologic Inpatient Consulting Service, Ritu Swali, Tyler D. Evans, Dillon Clarey, Corey Georgesen, Ashley Wysong

Graduate Medical Education Research Journal

Abstract

Introduction:

Inpatient dermatology consultations can bring a mixed bag of pathologies. Due to the highly specialized nature of dermatology and the lack of dermatologic training in medical school, the dermatologic team is consulted for matters that range from non-urgent to pressing. Pictures are a critical component of dermatology and greatly aid in the diagnosis of cutaneous diseases. In the inpatient setting, pictures can help streamline diagnosis and prevent unnecessary tests or procedures. The purpose of this study was to evaluate for the presence of pictures in patients’ chart after a dermatology consult had been placed through EPIC at the …


Alcohol Consumption Is Associated With Increased Cea Levels In Male Patients With Stage Iv Colorectal Cancer- A Single-Institution Retrospective Analysis, Lauren M. Keim, Alexander W. Praus, Walter S. Campbell, Kaeli K. Samson, Ashley M. Mohr, Martin Tobi, Benita L. Mcvicker Oct 2021

Alcohol Consumption Is Associated With Increased Cea Levels In Male Patients With Stage Iv Colorectal Cancer- A Single-Institution Retrospective Analysis, Lauren M. Keim, Alexander W. Praus, Walter S. Campbell, Kaeli K. Samson, Ashley M. Mohr, Martin Tobi, Benita L. Mcvicker

Graduate Medical Education Research Journal

Introduction: Alcohol use is an independent risk factor for liver metastasis, a major cause of morbidity and mortality in colorectal cancer (CRC) patients. Serum CEA level is an established prognostic indicator in CRC, yet the correlation with behavioral factors such as alcohol use remains to be defined. In a single-center review, we evaluated alcohol use, gender, and CEA levels in predicting advanced disease in CRC patients.

Methods: Retrospective analysis of UNMC patients diagnosed with CRC as the primary cancer between 2012-2019, stages I-IV, and age >19 with documentation of alcohol use. Univariable statistics were performed using Chi-Square and non-parametric tests. …


Health Service Utilization And Expenditure In Cardio-Metabolic Conditions In The United States Adults, Kavita Mosalpuria Aug 2021

Health Service Utilization And Expenditure In Cardio-Metabolic Conditions In The United States Adults, Kavita Mosalpuria

Theses & Dissertations

Metabolic syndrome is multicomponent risk factor for cardiovascular diseases (CVD) and type 2 diabetes that reflects the clustering of at least 3 cardiometabolic risk factors, among hypertension, impaired glucose regulations, hypercholesterolemia, and obesity. CVD are the leading cause of death in the U.S. CVD occur at earlier age and is a major cause of death and disability among people with diabetes. As compared to Japan, 13.3% to 44% of the excess CVD mortality in the U.S. can be explained by the metabolic syndrome. The prevalence of metabolic syndrome was 34.3% in 2007 to 2014 and it increases with age. Metabolic …


Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker Aug 2021

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …


How The Covid-19 Pandemic May Have Impacted Hospital Acquired Infection Rates, Mackenzie Lecy-Schoenherr Aug 2021

How The Covid-19 Pandemic May Have Impacted Hospital Acquired Infection Rates, Mackenzie Lecy-Schoenherr

Capstone Experience

Background: Hospital Acquired Infections (HAIs) are preventable; however, they continue to occur. Many HAI’s can be prevented by adhering to the Centers for Disease Control and Prevention (CDC) Healthcare Infection Control Guidelines. In late 2019 a novel virus, known as SARS-CoV-2, or COVID-19, emerged and spread across the globe. CDC recommended additional infection prevention and control practices during the COVID-19 pandemic, in addition to standard practices. This study will compare HAI rates before and during the COVID-19 pandemic as well as between COVID and non-COVID units.

Methods: HAI data collected pre-COVID-19 and during COVID-19 will be compared to determine …


Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson May 2021

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …


Fire Service Covid-19 Infection Prevention And Control Policy Comparison, Saaddedine Dichari May 2021

Fire Service Covid-19 Infection Prevention And Control Policy Comparison, Saaddedine Dichari

Theses & Dissertations

To date, there have been over 2.7 million deaths and more than 126 million cases attributed to the COVID-19 pandemic (JHU, 2021). This pandemic has affected nearly every aspect of daily life. Among those impacted are U.S. firefighters, as they provide many services beyond simply extinguishing structure fires and are frequently dual certified as emergency medical technicians. Many of the victims of this pandemic have relied on first responders to provide them with emergency medical care and hospital transport. When caring for these infected patients, firefighters have an increased risk of exposure and must be provided with adequate …


Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind May 2021

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …


Neurocognitive Impairment In People Living With Human Immunodeficiency Virus (Hiv): Risk Factors And Mortality, Zaeema Naveed May 2021

Neurocognitive Impairment In People Living With Human Immunodeficiency Virus (Hiv): Risk Factors And Mortality, Zaeema Naveed

Theses & Dissertations

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH) with clinical and public health implications. Studies have generated inconsistent results regarding etiological factors for NCI in PLWH and a brief user-friendly predictive tool is desirable in clinical practice to assess the probability of having NCI in PLWH. Furthermore, factors associated with clinically meaningful decline in neurocognitive status and survival disadvantage for patients with NCI are understudied in the post-cART era. The goal of this dissertation was to investigate factors associated with baseline NCI and neurocognitive decline and the association …


Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner May 2021

Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner

Theses & Dissertations

Despite effective regimens of combination antiretroviral therapy, individuals with HIV are still at higher risk for developing forms of cognitive impairment, with one of the most common behavioral abnormalities to manifest being motor dysfunction. This is an important consideration, as deficits in motor control likely contribute to higher-order cognitive impairments, which together, lead to functional dependencies in the ever-growing aging population of HIV-infected adults. While the neuroanatomical bases of motor dysfunction have recently been illuminated in people living with HIV (PLWH), there remains an open question regarding the molecular processes supporting the circuit-level neuronal dynamics that potentially serve these behavioral …


Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew May 2021

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …


Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb May 2021

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …


Characterization Of Di-Aryl Urea Compounds Against Acute And Chronic Toxoplasma Gondii, Austin Sanford May 2021

Characterization Of Di-Aryl Urea Compounds Against Acute And Chronic Toxoplasma Gondii, Austin Sanford

Theses & Dissertations

Toxoplasma gondii is an obligate intracellular parasite that has infected nearly 60 million individuals in the United States alone. Acute infection causes ill effects to the fetus in utero when mothers are primarily infected, and to immunocompromised individuals. Chronic infection consists of quiescent tissue cysts located primarily in brain tissue and is capable of reverting back to the acute stage causing severe toxoplasma encephalitis in immunocompromised individuals. Current treatments for acute infection are lacking while there are no approved treatments for the clearance of chronic infection. The aim of this research was to evaluate a family of di-aryl urea compounds …


Novel Mouse Model For Analysis Of Macrophage Function In Neuroblastoma, Gabrielle L. Brumfield, Shelby M. Knoche, Alaina C. Larson, Brittany Poelaert, Benjamin T. Goetz, Poomy Pandey, Don W. Coulter, Joyce C. Solheim May 2021

Novel Mouse Model For Analysis Of Macrophage Function In Neuroblastoma, Gabrielle L. Brumfield, Shelby M. Knoche, Alaina C. Larson, Brittany Poelaert, Benjamin T. Goetz, Poomy Pandey, Don W. Coulter, Joyce C. Solheim

Child Health Research Institute Pediatric Research Forum

Background: Neuroblastoma is the third most common childhood cancer and accounts for 12% of cancer-associated deaths in children under the age of 15. Patients with high risk neuroblastoma have a poor 5-year survival rate of less than 50%. Neuroblastoma tumors treated with the histone deacetylase inhibitor (HDACi) vorinostat have increased infiltration of macrophages with upregulated immune cell-surface receptors. Neuroblastoma cells release VEGF and M-CSF, which may alter intratumoral macrophage populations. VEGF has also been implicated in alteration of amyloid precursor protein family processing. Our lab demonstrated that amyloid precursor protein 2 (APLP2), a member of the amyloid precursor protein …