Diseases Commons^™

Colorectal Cancer Screening: Implementation And Evaluation Of A Screening Algorithm In A Rural Family Practice Clinic, Mollie M. Tate, Whitney Dubas

Doctor of Nursing Practice Projects: College of Nursing

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States and disproportionately affects rural populations. Although more than 90% of cases occur in adults older than 50 years, increasing incidence among younger adults prompted an update to national guidelines recommending screening beginning at age 45. Rural residents face multiple barriers to colorectal cancer screening (CRCS), including limited access to care, transportation challenges, lack of insurance, and absence of standardized screening processes in primary care. These barriers contribute to lower screening rates, delayed diagnosis, and poorer outcomes. Evidence demonstrates that CRCS reduces CRC morbidity and …

Z Variant Heterozygosity In Alpha-1 Antitrypsin Deficiency: Disease Risk And Treatment Implications, Craig P. Hersh, Jeffrey H. Teckman, Pavel Strnad, Aaron Hakim, Tomás P. Carroll, Ian P. Hall, Auyon J. Ghosh, Igor Barjaktarevic, Noel G. Mcelvaney, Joseph E. Kaserman, David A. Lomas, Charlie Strange, M Bradley Drummond, Stephen I. Rennard, Kathi E. Hanna, Virginia C. Clark, Monica P. Goldklang, Peg Iverson, Andrew A. Wilson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Individuals heterozygous for alpha-1 antitrypsin deficiency (AATD) have one copy of the normal "M" allele and one copy of an abnormal allele ("Z", "S", or another variant) in the SERPINA1 gene. Historically, evidence has been lacking to support the concept that heterozygotes are at increased risk for liver and/or lung complications compared to individuals homozygous for the M allele. However, growing evidence suggests that inheritance of a single Z allele increases the risk of disease in some individuals. The Alpha-1 Foundation convened a workshop on October 27, 2023, in Bethesda, Maryland that included stakeholders from the research, pharmaceutical, and …

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

Assessing Access To Orthopaedic Care For Patients With Osteogenesis Imperfecta, Annemarie K. Leonard, Kara Ayers, Lauren Faokunla, Kaeli Samson, Erika Carter, Tracy Hart, Maegen Wallace

Graduate Medical Education Research Journal

Background. Osteogenesis Imperfecta (OI) is a rare disorder caused by variations in collagen. Clinical manifestations include multiple fractures, short stature, scoliosis, blue sclera, hearing loss, and opalescent teeth. Patients often need many different medical providers frequently, which may place financial burdens on families. This study sought to identify and understand barriers to care for children with OI.

Methods. We utilized an Institutional Review Board (IRB)-approved survey for primary caregivers of children with OI. Questions included demographic data, type of health insurance, history of and reasons for insurance denials, access to multidisciplinary OI care, and travel to receive OI care. The …

Salt Vs. Scalpel: A Surprisingly Simple Solution To Pyogenic Granulomas, Richard M. Regester, Kimberly Eisenstein

Graduate Medical Education Research Journal

Background. Pyogenic granulomas (PGs) are benign vascular lesions commonly encountered in primary care settings. They are often linked to trauma, hormonal changes, infections, or medications. While traditional treatments such as excision, curettage, and silver nitrate application are the treatment of choice, recurrence is possible, and they may result in discomfort, anxiety, or scarring. This case highlights the successful use of salt packing, a low-cost, minimally invasive alternative, for a PG resistant to conventional therapy.

Case. A 57-year-old female presented with a 10 mm PG on the right ventral thumb, which bled intermittently and increased in size over three months. An …

Human Papillomavirus Vaccine Uptake Among U.S. Medical Residents In High-Exposure-Risk Specialties – A National Study, Madison Oxford, Christina Stetter, Arpit Dave

Graduate Medical Education Research Journal

Background. HPV vaccination is not required for the United States (U.S.) medical residents, despite their potentially high risk of iatrogenic exposure to the virus. We aim to evaluate vaccination status, patterns of HPV vaccine uptake, and perceived risk of iatrogenic infection among residents in high-exposure-risk specialties.

Methods. In spring 2023, an anonymous online survey was distributed via program directors and coordinators of all Accreditation Council for Graduate Medical Education (ACGME)-accredited Obstetrics & Gynecology, Family Medicine, Otolaryngology, and Dermatology training programs to assess residents’ vaccination status, HPV exposure, and HPV vaccine knowledge.

Results. Responses from 537 residents at programs located in …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Assessing The Association Between Total Cholesterol And Hospitalized Myocardial Infarction In Women Ages 32-70: An Analysis Of The Framingham Heart Study, Jolene L. Stapleton Duree

Capstone Experience: Master of Public Health

Objective

Heart disease is the leading cause of death in women that may go undiagnosed due to unexpected symptoms. The purpose of this analysis was to assess the effect of total cholesterol on the odds of hospitalized myocardial infarction (MI).

Methods

This analysis used a sample of 2,445 women from the Framingham Heart Study, an observational prospective cohort study. The exposure was total cholesterol, and the outcome was hospitalized MI. Logistic regression was used to estimate crude and adjusted odds ratios (OR). The adjusted models controlled for age, blood pressure, and diabetes. Effect modification by diabetes status was evaluated in …

Persistent Barriers To Implementation Of Long-Acting Injectable Antiretroviral Therapy, Jessica Hack, Adati Tarfa, Harlan Sayles, Nada Fadul

EMET Projects

No abstract provided.

Electronic And Regular Cigarettes Induce Transcriptional And Physiological Changes In Cardiomyocytes, Hesham Basma, Kajari Dhar, Jason Payne, Stephen I. Rennard, Brian D. Lowes

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Cigarette smoking is an important etiology for cardiac diseases and electronic cigarettes are increasing in popularity. In the current study, we assessed physiological and transcriptional changes in human induced pluripotent stem cell derived cardiomyocytes (iPS-CMs) after exposure to electronic cigarette extract (ECE) and conventional cigarette extract (CSE).

METHODS: iPS-CMS were plated on multi-electrode array plates (MEA), electrical and contractile properties were determined by Maestro Edge and computer assisted video analysis (MuscleMotion). Transcriptional profiles were accessed by direct digital mRNA detection of heart failure targeted genes.

RESULTS: Both ECE and CSE extracts significantly prolong beat period from baseline compared to …

Zinc Promotes Mitochondrial Health Through Pgc-1alpha Enhancing Bacterial Clearance In Macrophages Infected With Mycobacterium Avium Complex, Ruxana Sadikot, Prabagaran Narayanasamy, Zhihong Yuan, Deandra R. Smith, Daren L. Knoell

Journal Articles: Pulmonary & Critical Care Med

Mitochondria are increasingly recognized as important contributors to immune function, in addition to energy production. They exert this influence through modulation of various signaling pathways that regulate cellular metabolism and immune function in response to pathogens. Peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PGC-1α) is the primary transcription factor and regulator involved in mitochondrial biogenesis. Long known to be involved in immune function, zinc (Zn) is also required for proper mitochondrial function. It is increasingly recognized that many cellular immunometabolic activities are also Zn-dependent. Taken together, we investigated the role of Zn deficiency, both dietary and genetically induced, and Zn …

Gallium Β-Cyclodextrin Nanoparticles Containing Both Gallium Protoporphyrin And Gallium Nitrate Exhibit Antimicrobial Activity Against Nontuberculous Mycobacteria In Vitro And In Vivo, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pulmonary & Critical Care Med

Effective and safe antibiotics active against pathogenic mycobacterial species are needed. Iron is an essential element for bacterial survival. Ga(NO₃)₃ (GN) and Ga protoporphyrin (GP) as iron mimetics have each been shown to inhibit the iron metabolism and growth of various mycobacterial species. In this study, the dual cyclodextrin nanoparticle (CDGPGN) is prepared that carries GP and GN using a sonication homogenization technique to increase the efficacy of the combination therapy. CDGPGN shows a long-acting antimicrobial activity against Mycobacteroides abscessus residing in monocyte-derived macrophages (MDM). A murine pulmonary study showed that the CDGPGN also inhibited the growth …

Editing Approaches To Treat Alpha-1 Antitrypsin Deficiency, Derek M. Erion, Leah Y. Liu, Christopher R. Brown, Stephen I. Rennard, Humam Farah

Journal Articles: Pulmonary & Critical Care Med

TOPIC IMPORTANCE: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder most commonly due to a single G to A point mutation (E342K), leading to debilitating lung and/or liver disorders and is associated with increased mortality. The E342K point mutation causes a conformational change of the AAT protein resulting in its retention in liver hepatocytes. This reduces AAT secretion into the serum resulting in higher protease activities due to the lack of inhibition from AAT, causing damage to healthy lung tissue. The current standard of care for lung manifestations involves weekly IV augmentation therapy and is considered suboptimal for these patients. …

Pumping Iron, Straining Hearts: Androgen Building Cardiomyopathy In A Middle Aged Bodybuilding Enthusiast, Milan Terzic, Yash B. Patel

Graduate Medical Education Research Journal

A 46-year-old bodybuilder presenting with new onset dyspnea found to have a new onset non-ischemic cardiomyopathy (CM) attributed to exogenous trenbolone and testosterone use. Steroid cessation and guideline-directed heart failure therapy led to notable recovery in left ventricular function supported by global longitudinal strain, ejection fraction and symptomatology.

Anabolic steroid-induced CM involves multiple mechanisms including lipid disturbances, hypertrophy, reduced receptor sensitivity, and cell damage. This case emphasizes the importance of recognizing anabolic steroid misuse as a potential cause of non-ischemic cardiomyopathy in middle aged men. With prompt discontinuation of steroids, remained abstinence and early initiation of guideline-directed medical therapy, myocardial …

Association Between Agrichemical Mixtures And Pediatric Health Outcomes: Evidence From A Nebraska Population-Based Surveillance, Jabeen Taiba

Theses & Dissertations

Human exposure to environmental contaminants is associated with various pediatric health outcomes. Agrichemicals are a significant environmental risk factor for childhood cancers and congenital anomalies, and reduced exposure could improve pediatric health outcomes. Previous studies in Nebraska have explored the association between single pollutants and pediatric cancers and birth defects. However, it is important to estimate the overall effect of the agrichemical mixture on these pediatric health outcomes. In addition to environmental risk factors, several social vulnerability factors also contribute to increased agrichemical exposure and show disparities in pediatric cancers and birth defects. The objectives of this dissertation are to …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Trends, Predictors, And Outcomes Of Hepatic Encephalopathy Treatment At A Quaternary Transplant Center From 2012-2022, Patrick Twohig, Thoetchai Peeraphatdit, Kaeli Samson, Makayla Schissel, Lynette M. Smith, Kyaw Min Tun, Ellen Tan, Kyle Scholten, Jason Barbaretta, Kevin Brittan, Timothy Mccashland

Graduate Medical Education Research Journal

Background: Hepatic encephalopathy (HE) is a devastating complication of cirrhosis that increases mortality. Many patients do not receive guideline recommended HE treatment.

Our aim is to evaluate trends in HE treatment over time, variables associated with receiving treatment, and outcomes based on the type of treatment received.

Methods: Retrospective single-center cohort study of hospitalized patients with HE from July 2012 – June 2022. HE treatment was defined as receiving lactulose, rifaximin, or combination therapy.

Results: A total of 1,683 unique patients were included, 72% of patients received HE treatment. Fewer HE patients received any treatment in 2022 (65.9%) compared to …

Management Of Variceal Hemorrhage From Extensive Portal Vein Tumor Thrombus In Hepatocellular Carcinoma And Untreated Pheochromocytoma: A Case Report, Patrick Twohig, Kishan Patel, Tomoki Sempokuya, Chijoke Enweluzo, Lyudmila Muinov, Ishfaq Bhat

Graduate Medical Education Research Journal

Background: Over 600,000 people in the United States (U.S.) have liver cirrhosis. It is estimated that 30% of patients with compensated cirrhosis and 60% of patients with decompensated cirrhosis will develop varices in their lifetime, with an incidence rate of new varices at 9% per year. Fifty percent of patients with esophageal varices will experience bleeding at some time. Pheochromocytoma is a rare catecholamine secreting adrenal gland tumor that occurs in 2-8 people per every 1 million people in the general population. Standard treatment for variceal bleeding includes endoscopic band ligation and/or radiologic embolization along with non-selective beta blockers. However, …

Impact Of Sepsis Education For Emergency Department Staff: A Quality Improvement Project, Shayna E. Thoene, Shannon Mills

Doctor of Nursing Practice Projects: College of Nursing

Background: Sepsis continues to be a critical issue worldwide. New sepsis guidelines instituted by the Centers of Medicare and Medicaid Services (CMS) list evidence-based standards to comply with regarding care for sepsis patients. To help a new acute care facility meet compliance, a sepsis educational program has been developed to assess staff knowledge and confidence in caring for these patients.

Methods: This quality improvement (QI) project was developed using a pre-post study design to assess the impact of implementing a sepsis educational program for emergency department staff at this new acute care institution. A sepsis educational program was derived from …

Patient-Centered Preimplant Education Session And Bi-Weekly Text Message Adherence Reminders In Patients With A Newly Implanted Cardiomems® Device: A Quality Improvement Study, Elizabeth M. Miller, Alicia Abboud, Audrey Cooper

Doctor of Nursing Practice Projects: College of Nursing

Rationale

Heart failure is a deadly disease, affecting over 6.2 million individuals and costing the United States an estimated 30.7 billion dollars (Virani et al., 2020). By 2023, heart failure costs in the United States are estimated to grow to 70 billion dollars with 75-80% of these costs attributed to inpatient hospitalizations (Heidereich et al., 2022). The CardioMEMs® is a small device placed in the patient’s pulmonary artery via a minimally invasive procedure by an interventional cardiologist. The use of remote patient data from the CardioMEMs® device has been shown to reduce hospital re-admissions, facilitate tailored medication management, detect increased …

Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar

Theses & Dissertations

Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection …

The Physiological Significance Of Nitric Oxide Synthase In Staphylococci, Ryan M. Singh

Theses & Dissertations

Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO^•), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO^•, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

The Effect Of Repetitive Transcranial Magnetic Stimulation On Brain And Cognitive Variables In Patients With Amnestic Mild Cognitive Impairment, Connor J. Phipps

Theses & Dissertations

Healthy and pathological aging processes can impact human memory. Current interventions for clinical memory impairment offer little opportunity for restoration of memory ability. Fortunately, a novel therapy in the form of repetitive transcranial magnetic stimulation (rTMS) has exhibited promise in this regard. In healthy adults, rTMS of the angular gyrus (AG) has been reported to improve memory. The current study sought to determine the generalizability of these findings to individuals with clinical memory impairment by administering a clinical trial replicating an rTMS protocol reported to improve hippocampal-dependent memory in healthy individuals to individuals with amnestic mild cognitive impairment (aMCI). Individuals …

Unraveling The Role Of Gjb3 In Lung Adenocarcinoma, Swathi M. Priyanka

Theses & Dissertations

Lung cancer stands as a leading cause of cancer-related mortality worldwide, with small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) comprising its primary categories. NSCLC, representing nearly 85% of cases, exhibits a 5-year survival rate of less than 21%. Among NSCLC subtypes, lung adenocarcinoma (LUAD) prevails as the most common, followed by squamous cell carcinoma and large cell carcinoma. Gap junctions are crucial for intercellular communication and cellular homeostasis maintenance, demonstrate altered expression patterns in various diseases, including cancer. Gap junction beta 3 (GJB3 or Connexin31) exhibits significant expression in both preclinical and clinical LUAD samples, prompting investigation into …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Multimodal Investigations For The Identification Of Surgically Relevant Brain Areas, Kevin Tyner

Theses & Dissertations

Epilepsy is a neurological disease leading to recurrent and unpredictable seizures. Patients can be diagnosed as focal onset, where the seizure focus resides in one hemisphere; generalized onset, where seizure foci reside in both hemispheres; or unknown onset. Anti-seizure medications are the first line of treatment, and those whose seizures cannot be controlled with medication are diagnosed with drug-resistant epilepsy (DRE). For patients diagnosed with focal onset epilepsy to achieve seizure freedom, surgical resection of the epileptogenic zone (EZ), the region of the brain that is both necessary and sufficient for initiating seizures, is required. The EZ is a theoretical …

Cardiovascular Disease Risk Reduction Program For Hispanics In The Us Midwest: A Culturally Adapted Intervention, Armando De Alba

Theses & Dissertations

Cardiovascular disease (CVD) represents the second leading cause of death in Nebraska (NE), accounting for approximately one in every five deaths. In the state, there are marked ethnic and rural-urban disparities in the prevalence of chronic diseases and resultant deaths. For instance, while the rates in NE of coronary heart disease and myocardial infarction between 2001 and 2010 decreased among non-Hispanic Whites, the rates for Hispanics almost tripled. There is little evidence of CVD risk factor reduction strategies being implemented in Midwestern areas and Hispanic populations.

One promising approach for reducing CVD risk involves health education and lifestyle modification programs …