Virus Diseases Commons^™

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 …

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

EMET Projects

No abstract provided.

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)]. …

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 …

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 …

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 …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Understanding And Quantifying Bioaerosol Fate Within The Aerobiological Pathway: Physical Transport, Environmental Decay, And Mitigation, Sean Kinahan

Theses & Dissertations

The recent COVID-19 pandemic has highlighted the need for better tools to understand and characterize phases of the aerobiological pathway, a model for understanding how infectious bioaerosols are sourced, generated, transported, deposit, and affect human health. This dissertation presents validation of methodologies for studying transport of airborne biological agents and variations on their consequences, especially focusing on their physical and chemical fate. Chapter 1 focuses on a parallel comparison of two methods of aging bioaerosols in real-world outdoor environments with complex sunlight, atmospheric chemistry, and pollutants. Both capture on microfibers and the use of Goldberg rotating drums to keep a …

Center Based Cardiac Rehabilitation Outcomes Associated With Covid-19 Pandemic: A Retrospective Comparative Cohort Study, Haley Williams, Kayla Woodworth

Doctor of Nursing Practice Projects: College of Nursing

Background: Traditional cardiac rehabilitation (CR) is a multidisciplinary, multifaceted program for cardiac patients. Throughout the Covid-19 pandemic, health care, including center-based CR (CBCR) programs, were closed to in-person sessions. Even with the return to CBCR participation, patient outcomes may have been affected by this disruption in care. The goal of this study was to determine if CR participation outcomes differed before and after CBCR program closure due to Covid-19.

Methods: A retrospective comparative cohort design was used to examine CR participant outcome data before and after the Covid-19 pandemic. Convenience sampling of CR participants at a large, urban …

Assessing The Impact Of Ebola Virus Inoculum Size On Likelihood Of Infection, Joseph Lukowski

Capstone Experience: Master of Public Health

Background: Indirect transmission of Ebola virus disease (EVD) is not uncommon but is poorly understood. Improving the understanding of the potential risk of EVD transmission from fomites should result in new or updated prevention or control measures for suspected or confirmed EVD cases or outbreaks.

Objective: This study aims to compile and understand pertinent data from peer-reviewed literature, establish the dose-response relationship between inoculum doses introduced to mucous membranes, and finally estimate the risk of EVD transmission from fomites.

Methods: A literature search was conducted through PubMed to obtain relevant data. This study employed this data to perform Poisson regression …

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 …

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 …

Characterization Of Aerosols Produced By Common Orthodontic Procedures, Anna R. Schoettger

Theses & Dissertations

Introduction: Aerosols can harbor active viruses, including SARS-CoV-2, making it vital that clinical protocols implemented in the orthodontic office be based on which procedures produce aerosols. Research shows that various procedures in the field of orthodontics generate aerosols, however, there is a lack of consensus as to which procedures should be deemed aerosol-generating procedures (AGPs). The current study aimed to better understand aerosol production of various orthodontic procedures. Methods: Orthodontic procedures were performed in a closed-room dental operatory on acrylic teeth mounted onto a dental manikin. Procedures performed included: debonding, bonding, and repositioning of one bracket. Variations introduced included: high-speed …

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 …

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 …

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 …

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 …

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 …

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 …

Customized Blister Packaging For Patients Living With Hiv: Assessment Of Patient Attitudes And Satisfaction, Holly Groteluschen, Harlan Sayles, Rebecca Osborn, Joshua P. Havens, Sara Bares, Jasmine R. Marcelin

Graduate Medical Education Research Journal

Adherence to antiretroviral medication results in reduced HIV transmission and improved health outcomes, yet challenges with medication adherence remain. A Collaborative Care Program was developed with a community pharmacy integrating a multi-dose adherence packaging service. We surveyed program participants to assess their satisfaction with this program and found an overall positive sentiment toward the program, that the program helped with reducing missed doses, and all patients would recommend the program to others.

Endoscopic Removal Of Fractured 3d-Printed Nasopharyngeal Swabs From The Olfactory Cleft During Covid-19, Matthew Miller, Kristy Carlson, Jayme Dowdall, Christie Barnes, Sam Pate

Graduate Medical Education Research Journal

The severe acute respiratory syndrome SARS-CoV-2 pandemic has posed significant challenges to hospital and public health systems in the United States. In response to a shortage in nasopharyngeal swabs, our institution developed, tested, and deployed 3D-printed swabs to obtain a specimen for testing. A patient was tested in preparation for a scheduled Esophagogastrodeuodenoscopy. During the procedure the swab broke and a portion remained in the superior meatus and olfactory cleft. This case study describes the process of locating and removing the broken sections of the 3D-printed swab. In response to this incident, 3D-printing teams test swabs for sample collection and …

Effect Of Cigarette Smoking On Cd4 Count And Viral Load Among Hiv Patients Attending Treatment At Nebraska Medicine, Chacha Josiah Mwita

Capstone Experience: Master of Public Health

Background

Smoking is known to have a negative impact on both morbidity and mortality in people living with HIV (PLHIV). However, there is inconsistent information about the role of smoking on markers of HIV disease progression (CD4 count and HIV viral load). This study examined the effects of cigarette smoking on markers of HIV disease progression among PLHIV at Nebraska Medicine.

Methods

A retrospective cohort study was conducted utilizing electronic health information of 604 PLHIV who attended treatment at Nebraska Medicine between 2012 and 2020. Multiple linear regression was used to model the effects of smoking on the mean change …

Sé Un Héroe Tú También, Samantha S. Rohe, Sophie Cemaj

Books: Pediatrics

This children's book explains COVID-19 and how to decrease the incidence of transmissions.

Be A Hero Too, Samantha S. Rohe, Sophie Cemaj

Books: Pediatrics

This children's book explains COVID-19 and how to decrease the incidence of transmissions.

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Hiv-1 Elimination In Humanized Mice, Hang Su

Theses & Dissertations

Human immunodeficiency virus type one (HIV-1) exclusively infects humans and chimpanzees. Therefore, animal models are required for all investigations of viral pathogenesis, therapy and cure. Immunodeficient mice transplanted with human hematopoietic stem cells, termed humanized mice, support the development of multiple human cell lineages throughout the cell’s life span. To this end, we used humanized mice to evaluate the dynamic changes of host immunologic and viral profiles during both acute and chronic HIV-1 infection. We identified the temporal and spatial distribution of HIV-1 cell and tissue compartment infections and outlined correlations made between viral progression and host immunity by comparing …

Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire

Theses & Dissertations

Antiretroviral therapy (ART) requires lifelong daily dosing to suppress viral replication, restore or maintain immune function and improve quality of life. As an alternative, long-acting (LA) antiretrovirals (ARVs) aim to deliver therapeutic drug concentrations over an extended period, ultimately requiring monthly or even more extended dosing intervals. Specifically, the success of recent clinical trials examining LA cabotegravir and rilpivirine (CAB and RPV LA) highlight the advent of these novel HIV-1 therapeutics. Further optimization of LA dosage forms are required and rests upon improving dosing frequency, injection volumes and tissue distribution to viral compartments. To this end, we report the synthesis …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Examining The Impact Of Hiv Medical And Social Case Management Program On Viral Load For Clients Living With Hiv/Aids In Nebraska, Abdulla Munir

Capstone Experience: Master of Public Health

Abstract

Case management (CM) is one of the standard practices that has been implemented since 1990 to help people living with HIV/AIDS (PLWHA) in the United States. The program is designed for low-income populations and it aims to address the barriers related to access to health care and improve the HIV outcomes. Previous studies identified a positive association with the provision of CM and improvement in viral outcomes. Increasing the viral suppression rates among HIV diagnosed individuals proved to reduce the risk of transmitting the infection, and disease incidence. Although CM program is provided to Nebraskans diagnosed with HIV, but …