Digital Commons Network^™

Angiopoietin-Like4 Is A Novel Marker Of Covid-19 Severity, Pavan K. Bhatraju, Eric D. Morrell, Ian B. Stanaway, Neha A. Sathe, Avantika Srivastava, Radu Postelnicu, Richard Green, Adair Andrews, Martin Gonzalez, Christopher J. Kratochvil, Vishakha K. Kumar, Tien-Ying Hsiang, Michael Gale, George L. Anesi, David Wyles, M. Jana Broadhurst, David Brett-Major, Vikramjit Mukherjee, Jonathan E. Sevransky, Douglas Landsittel, Chi Hung, William A Altemeier, Sina A. Gharib, Timothy M. Uyeki, J. Perren Cobb, Janice M. Liebler, David R. Crosslin, Gail P. Jarvik, Leopoldo N. Segal, Laura Evans, Carmen Mikacenic, Mark M. Wurfel

Journal Articles: Epidemiology

IMPORTANCE: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.

OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes.

DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New …

Understanding The Perceived Risk And Biopsychosocial Impact Of The Covid-19 Pandemic On People Living With Hiv And Pre-Exposure Prophylaxis Users In Nebraska: A Mixed Methods Approach, Titilola O. Labisi

Theses & Dissertations

The COVID-19 pandemic disrupted HIV care and prevention services. COVID-19 guidelines required physical and social distancing, resulting in movement restrictions and limited healthcare services. People living with HIV (PLWH) may be more vulnerable to the pandemic’s impact due to immune suppression and socioeconomic status than people without HIV. Consistent use of pre-exposure prophylaxis (PrEP), condoms, and regular sexually transmitted infection tests are critical strategies for HIV prevention. The pandemic’s impact on PLWH have not been thoroughly studied, and whether PLWH may be more impacted than PrEP users is inconclusive.

This research aimed to use an explanatory sequential mixed methods design …

Hepatocyte-Hepatic Stellate Cell Axis In Potentiation Of Alcohol And Hiv-Induced Liver Injury, Moses O. New-Aaron

Theses & Dissertations

Human Immunodeficiency Virus (HIV) remains a global threat, with approximately 38.4 million active infections and 33 million HIV-related deaths since the first case. While many may be tempted to think of HIV as a relic of the past, emerging data suggests otherwise. By the end of 2021, approximately 1.5 million HIV incidences and 650 000 mortalities were reported globally. The etiologies of HIV-related mortality are numerous. Liver disease is one of the leading etiologies of HIV-related mortality, especially in recent times of antiretroviral therapy (ART)-induced longevity among people living with HIV (PLWH). While co-infections with hepatotropic viruses notoriously contribute to …

Gender Differences In Breast Cancer Treatment Decisions And Related Survival: A Study Using The National Cancer Database, Shamim Shahi

Theses & Dissertations

Despite increasing incidence, male breast cancer (MBC) remains understudied in almost all aspects of disease management. MBC patients are more likely to be diagnosed with larger tumors, at an advanced stage, and to experience poorer survival than female patients. There is a need to identify modifiable factors that can improve MBC patients’ survival.

This dissertation aimed to investigate whether there was a difference in the refusal of recommended treatments and related survival, by gender, in breast cancer patients enrolled in the National Cancer Database. Specifically, we conducted separate analyses for four treatments: hormone therapy, chemotherapy, radiation therapy, and surgery. Then, …

A Study To Determine The Most Important Leadership Skills For Entry-Level Public Health Practitioners, Taelyr Weekly

Theses & Dissertations

Objective: This study 1) identifies the top leadership skills needed for entry-level local public health department employees, 2) provides employee self-assessment ratings in importance, preparation, and proficiency of select leadership skills, and 3) compares the self-assessment and supervisor ratings of select leadership skills to assess how prepared and proficient employees are. Participants: A sample of positional leaders (n=15) from Nebraska’s local health departments provided results for the top leadership skills for entry-level local public health department employees. Employee self-assessment ratings (n=18) and paired samples of employees and supervisors (n=12) produced results on the importance, preparation, and proficiency of …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige

Theses & Dissertations

Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …

Crispr Technology As An Antiviral In Dsdna And Ssrna Viruses, Cathryn Mayes

Theses & Dissertations

The COVID-19 pandemic highlights the necessity of emergency response and pandemic preparedness, especially for emerging viral threats. Currently, virus-specific vaccines and antivirals are the primary tools to combat viral diseases; however, broad-spectrum antivirals that target more than one virus species could provide additional protection from emerging and re-emerging viral diseases (Andersen et al. 2020; Zhu et al. 2015; Hickman et al. 2022).

Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated endonucleases have become recently utilized as potential antiviral strategies due to their high specificity, efficacy, and versatility (Najafi et al. 2022). While CRISPR-based antivirals have previously been used to target specific …

Aerosols In Orthodontics: Characterization Of Particle Size And Travel Distance, Donte Jochum-Nesbitt

Theses & Dissertations

Introduction: Aerosol production is a key contributor to occupational risk and disease transmission in the dental clinic. These aerosols can host harmful pathogens, such as SARS-CoV-2. Considering the 2020 pandemic, researchers endeavored to bolster the existing body of literature related to disease transmission via aerosols and droplets to provide better recommendations for infection control. This investigation aims to support that mission by characterizing the risk to orthodontic professionals and patients based on aerosolized particle size and travel distance. Methods: The experimental protocol used in this study was validated through a smaller scale pilot study in 2021. High- and Low-risk orthodontic …

Essential Protections For Essential Workers: Ethical Considerations For Infection Prevention And Control, Abigail E. Lowe

Theses & Dissertations

Prior to the COVID-19 pandemic, ethical guidance for workers during epidemics and pandemics centered on healthcare workers, which meant there was not guidance to address critical contextual issues for many on the frontlines of the pandemic. Meat processing workers are a key example of workers deemed essential during the COVID-19 pandemic and facing conditions of elevated risk without adequate public health guidance or resources to control disease spread. Meat processing workers are an underserved, resource-limited, and vulnerable workforce that face occupational health and safety risks. Meat processing and other essential workers have heightened health disparities due to the social determinants …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

An Epidemiological Synthesis Of Emerging And Re-Emerging Zoonotic Disease Threats In Cameroon, 2000-2022 And Community Stakeholder Mapping, Nancy Tahmo

Capstone Experience: Master of Public Health

Introduction: Population factors such as urbanization, socio-economic, and environmental factors are driving forces for emerging/re-emerging diseases in Cameroon, and the effects of these are experienced differently across demographics. Indigenous rainforest communities in the Congo Basin, for example, suffer worse health outcomes compared to neighboring communities, like the Pygmies, who have a life expectancy of 22 years less than neighboring Bantus. It is important to characterize the risk of exposure of these vulnerable communities and map out, through a systematic review, descriptive epidemiological data around zoonoses, to inform preparedness and research efforts.

Methods: Following the PRISMA guidelines, a protocol was registered …

Evaluating How Physical Activity Affects The Perception Of Resilience In Box Butte County, Nebraska, Eric Pulver

Capstone Experience: Master of Public Health

Physical activity is one of the modern hallmarks for good health in individuals and the public, in general. Resiliency is a growing concentration in all levels of disaster preparedness where the focus is on how to deal with the growing number of disasters stemming from global climate change. This research project’s aim is to look at the possible relationships between physical activity and resiliency in a rural Nebraska population. This was done with the use of a cross-sectional study utilizing a fifteen-question survey to gather demographics, assess the amount of physical activity, and then apply a perception of resilience tool …

Evaluating How The Impacts Of Climate Change On Arizona's Water Supply Will Influence Public Health, Patricia Wrona

Capstone Experience: Master of Public Health

Over the last century, Arizona’s climate has increased more than 1.1 to 1.4 degrees Celsius or 2 to 2.5 degrees Fahrenheit. The temperature in Arizona is expected to increase an additional 2.2°C to 2.8°C in the next 40 years. Climate change poses various health and environmental hazards for the residents of Arizona. One of the most significant impacts is on water supply. As temperatures continue to rise in the desert, the demand for water will increase while the water supply will reduce. A literature review and program evaluation were conducted to evaluate how the impacts of climate change on Arizona’s …

An Analysis Of Climate Factors And Their Relationship With Lyme Disease And West Nile Virus In California From 2011 To 2020, Emma Dubas

Capstone Experience: Master of Public Health

The World Health Organization estimates that approximately one-sixth of illnesses and disabilities suffered worldwide are due to vector-borne diseases, and more than half of the world’s population is at risk. Additionally, vector-borne diseases have significant socioeconomic impacts and inflate health inequities, with the greatest burden on poor populations. Lyme disease is the top tick-borne disease in the state of California and West Nile virus (WNV) is the top mosquito-borne disease in the state of California. Vector-borne diseases have a high sensitivity to climatic factors. Research shows that ongoing trends of increasing temperature and varying weather conditions will weaken recent global …

Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez

Theses & Dissertations

Pancreatic cancer is currently the 3rd leading cause of all cancer-related deaths, with a 5-year survival rate remaining at 10%. The current standard treatment of care and a lack of effective diagnostic markers leaves patients with a dismal prognosis at advanced stages of the disease. This thesis research evaluated the effect of ApoE-expressing macrophages in the spleen. First, we aimed to assess the ApoE expression in the spleen of pancreatic tumor-bearing mice. Results showed that ApoE expression in splenic macrophages increased as the disease progressed. In addition, we saw a significant increase in marginal zone metallophilic macrophages and red pulp …

Investigating The Role Of Sphingosine Kinases During Alphavirus Infection, Opeoluwa Oyewole

Theses & Dissertations

Several alphaviruses, critical human pathogens, have re-emerged in recent years. Alphaviruses are found on all continents and infect both invertebrates and vertebrates, including some aquatic animals. They are classified as arboviruses because hematophagous arthropods transmit them. Based on the symptoms they cause, alphaviruses are classified as either arthritogenic or encephalitic.

Rising global travel has led to outbreaks of infections in new regions, increasing the geographical ranges of alphaviruses and causing new infections in susceptible hosts. Currently, there are no approved prophylactic or therapeutic measures to prevent or treat alphavirus infections; prevention measures have focused on vector control. These measures are …

Applications Of Population Pharmacokinetic Modeling In People Living With Hiv, Michelle M. Pham

Theses & Dissertations

Population pharmacokinetic modeling has become an important tool for the individualization of medicine in HIV care and clinical pharmacology in general. This dissertation explores many applications of population pharmacokinetic modeling to help identify drug exposure, drug-drug interactions, and sources of variability in populations living with HIV. Comprehensive HIV care involves simultaneous treatment of the disease and any co-infection and/or co-conditions.

The first objective was to identify potential drug-drug interactions affecting combination antiretroviral therapy (ART) consisting of efavirenz, tenofovir disoproxil fumarate and emtricitabine, from concomitant use of chemotherapy agents. Three models were developed with sparse sampling to characterize efavirenz, emtricitabine, and …

Optimizing Antiretroviral Therapy With Modern Rifapentine Containing Tb Treatment, Anthony T. Podany

Theses & Dissertations

In the past decade there has been a multitude of phase 3 clinical trials targeting treatment shortening for tuberculosis (TB). The synthetic rifamycin derivative rifapentine (RPT) has been at the forefront of many of the treatment shortening approaches. RPT possesses greater potency and a longer pharmacokinetic (PK) half-life (t_1/2) as compared with the long used rifamycin, rifampin (RIF). For TB preventative treatment, a 3-month, once weekly regimen of RPT and isoniazid (INH; 3HP) was shown to be as effective as 9-months of daily INH therapy in the PREVENT TB trial. Similarly, a 4-week course of daily RPT and …

Examining Mental Health Disparities In A Rural County: A Community Health Needs Assessment Analysis, Dustin M. Schulz

Capstone Experience: Master of Public Health

Over 20% of adults in the United States experience some form of mental illness each year. Those residing in rural areas can see increased prevalence of mental illness, and typically face disparities in access and availability of services for mental health. The goal of this project was to examine the impact of mental health in Woodford County, Illinois using data collected through the 2022 Community Health Needs Assessment (CHNA) process, with the intent of identifying areas of improvement that could be implemented at the local level. Analysis of the CHNA data was conducted using frequency analysis in SAS 9.4 through …

An Analysis Of Demographics And Risk Factors Associated With Increasing Syphilis Cases In Iowa, Eleanore H. Nelson

Capstone Experience: Master of Public Health

Background:

Syphilis is easily detectable and treatable with the appropriate medical attention, yet national incidence rates have been on the rise since reaching an all-time low in 2000 (Shockman et al, 2014). Similar to HIV, men who have sex with other men (MSM), represent most syphilis transmission, yet in recent years, syphilis rates have concerningly increased among both genders and among all racial/ethnic groups (CDC, 2019).

Methods:

Surveillance data was collected on all syphilis cases reported to the Iowa Department of Public Health (IDPH) regarding demographics and risk factors of cases. Variables were analyzed using chi-square and Fisher’s exact tests, …

Back Cover Vol 4 Issue 1

Graduate Medical Education Research Journal

No abstract provided.

Introducer-Free Mis-Assisted Ventriculoperitoneal Shunt Placement: A Technical Document, Eric Chen, Patrick Opperman, Edson Deoliveira, Priscila Rodrigues Armijo, Vishal Kothari, Daniel Surdell

Graduate Medical Education Research Journal

Background

The placement of the distal catheter of a ventriculoperitoneal shunt (VPS) can be challenging in patients with a large body habitus. Given the complications associated with ventriculoperitoneal shunts and known infection risk of obese patients, new techniques for VPS placement that bypass the abdominal fat must be sought. By avoiding the abdominal fat, decreased complications and infection risk may be possible.

Objective

The objective of this technical document is to describe a laparoscopic approach to the abdominal cavity during ventriculoperitoneal shunt surgery that makes use of a direct tunneling technique into the peritoneal space.

Methods

We perform a ventriculoperitoneal …

Scholarly Activity In Residency: A Needs Assessment Of Challenges And Proposed Solutions, Jonathan Hall, Jana L. Wardian Phd, Jasmine R. Marcelin

Graduate Medical Education Research Journal

Introduction

Resident physician participation in scholarly activity is associated with significant benefits ranging from trainees’ personal development to improved quality of patient care. Residency programs have taken varied approaches to improve resident engagement in scholarship, though interventions have demonstrated mixed results regarding objective measures of scholarly productivity. Concerns regarding waining interest in scholarship amongst internal medicine residents prompted a department-wide needs assessment to evaluate opportunities for scholarship and challenges preventing resident participation.

Methods

A web-based survey was developed and distributed to Department of Internal Medicine faculty and residents at the PGY2 level or higher and recent graduates within the last …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Exploring Host-Pathogen Interactions Of The Ebola Virus Ribonucleoprotein Complex, M. Jane Morwitzer

Theses & Dissertations

Ebola virus (EBOV) causes a severe hemorrhagic fever in humans that is oftentimes lethal, emerging as a global public health threat in recent years. Understanding the host factors that contribute to the dynamic states and functions of the EBOV ribonucleoprotein (RNP) complex could potentially advance the development of therapeutics. The viral architecture of the EBOV RNP complex has been defined but host protein interactions that modulate viral replication have largely gone unaddressed. EBOV nucleoprotein (NP) and viral protein 35 (VP35) play critical roles in viral replication and capsid assembly, comprising two major components of the RNP complex. Elucidation of host …

Development Of Perfluorocarbon Nanoemulsions For Delivery Of Therapeutic Nucleic Acids, Ling Ding

Theses & Dissertations

Local pulmonary administration of therapeutic siRNA represents a promising approach to the treatment of lung fibrosis, which is currently hampered by inefficient delivery. Pancreatic cancer (PC) is a fatal human cancer whose progression is highly dependent on the nervous tumor microenvironment. siRNA delivery has been well studied as a promising therapeutic agent for several disease, including the pulmonary fibrosis and cancer. Perfluorocarbon nanoemulsions have been studied in the treatment of various diseases as drug delivery systems. We report development of perfluorooctylbromide (PFOB) nanoemulsions as a platform to facilitate delivery and penetration of a therapeutic siRNA to pulmonary fibrosis lung and …

Leukocyte Subsets In The Peripheral Blood And Spleen Of Gastrointestinal Cancer Patients, Kathryn E. Cole

Theses & Dissertations

In 2022, an estimated 62,210 people will be diagnosed with pancreatic ductal adenocarcinoma (PDAC) and approximately 49,830 will die from the disease. Current treatment strategies for gastrointestinal (GI) cancer patients, such as PDAC, have shown limited benefit, suggesting the need to develop novel, multimodality therapeutic approaches. Adoptive cellular therapy (ACT) using autologous tumor infiltrating lymphocytes (TILs) has shown efficacy in patients with melanoma; however, this approach is costly and requires extensive cell culture for sufficient numbers of T-cells for infusion. GI cancer patients with borderline resectable disease, whose primary tumor is adjacent to the splenic vasculature, can sometimes undergo a …

1-Check Unmc Mobile App Usage: A Quantitative Analysis Of The Data, Molly Pofahl

Theses & Dissertations

As COVID-19 cases continued to rise in Nebraska, universities and colleges were faced with unique challenges in the effort to continue providing quality education for students. The University of Nebraska Medical Center (UNMC) took on especially difficult challenges due to its status as an academic medical center. By the Fall of 2021, students, faculty, and staff were beginning to return to campus. The 1-Check UNMC app was created to help keep sick people from coming to campus. The UNMC community was expected to screen themselves for COVID-19 using this app each day before coming to campus. This thesis is an …

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

MD Honors Theses

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 …