University of Nebraska Medical Center
University of Nebraska Medical Center Research: DigitalCommons@UNMCNot a member yet
10909 research outputs found
Sort by
Quaternized Chitosan Derivatives Inhibit Growth and Affect Biofilm Formation of Staphylococcus Aureus
Antimicrobial resistance (AMR) poses a global health threat, severely impeding the effective treatment of bacterial infections and jeopardizing the safety of routine medical procedures. Methicillin-resistant Staphylococcus aureus (MRSA) is particularly problematic because of its resistance to beta-lactams and the ability to form resilient biofilms. Conventional antibiotics, including last-resort options, have serious side effects and may contribute to further resistance. Chitosan, a natural biopolymer, offers a promising alternative due to its biocompatibility and antimicrobial properties, though its effectiveness against biofilms is limited. Recent studies suggest that increasing the positive charge density and adding hydrophobic moieties to chitosan, can enhance its antimicrobial properties. In this work, the antibacterial activity of quaternized chitosan derivatives against AMR S. aureus strains was assessed. Quaternization of chitosan\u27s amino group and introduction of hydrophobic side chains was found to significantly inhibit bacterial growth in both methicillin-sensitive (MSSA) and MRSA strains. Notably, nanofibrous materials composed of polyethylene oxide and hexyl-modified chitosan demonstrate alterations in S. aureus biofilm development, leading to significant accumulation of dead cells. Combined, these results highlight the potential of modified chitosan derivatives as effective antimicrobial agents for surface treatments and medical device coatings, particularly in applications where antibiotics are traditionally used, such as biofilm-prone environments
Electronic and Regular Cigarettes Induce Transcriptional and Physiological Changes in Cardiomyocytes
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 control after 2 days of exposure (0.74 ± 0.14 s for ECE and 0.78 ± 0.02 s for CSE). Prolonged time to peak in ECE and CSE were also significantly prolonged compared to control with a P \u3c 0.05 (487 ± 44, 373 ± 21 and 312 ± 8 ms respectively). In addition, both ECE and CSE decrease cardiomyocyte contractility in a similar fashion. ECE exposed cells have 25 genes in discovery and 33 genes in validation experiments that were significantly different compared to control with P \u3c 0.05. CSE exposed cells, however, do produce more profound effects on transcriptional profiles of heart failure with 53 genes in discovery and 40 genes in validation compared to control group with P \u3c 0.05. In summary, both ECE and CSE are sufficiently toxic to impair cardiac physiology and alter myocyte gene expression. Transcriptional profiles of heart failure related genes are consistent with cigarettes altering expression of sarcomeric proteins and calcium handling.
CONCLUSION: Human cardiomyocytes can be utilized to study the molecular biology and toxicology of electronic and conventional cigarettes
Restoring Trust in Public Health: An Analysis of the Lasting Implications of the COVID-19 Pandemic Response on Community Trust in Public Health in Nebraska
Background and Significance
Public trust is essential for effective public health efforts. In Nebraska, as in many regions, the pandemic response exposed strengths and vulnerabilities in the public health system. Misinformation, political discourse, inconsistent messaging, and poor communication contributed to growing mistrust, threatening the long-term success of public health programs and initiatives. While national trends have been studied, Nebraska-specific research remains limited.
Methods
An original descriptive survey was designed and administered to public health professionals in Nebraska to assess their perceptions of public trust in the local public health system before and after the COVID-19 pandemic. The survey also explored the ongoing impact of mistrust on public health initiatives and identified strategies implemented in Nebraska to rebuild and maintain trust. A total of 54 public health professionals completed the survey.
Results
Survey results indicate that maintaining public trust during the COVID-19 pandemic response was a challenge for 92.5% of local health department respondents in Nebraska. Additionally, 74% indicated that mistrust continued to negatively impact non-COVID public health programs to some degree. Despite efforts to rebuild trust, 81.5% of respondents emphasized that trust-building strategies must be a priority for local health departments. While many respondents (48.1%) believe their department has the capacity to restore public trust, significant challenges remain in regaining public confidence.
Conclusion
This study highlights the lasting impact of the COVID-19 pandemic on public trust in public health in Nebraska. While many departments are actively working to rebuild trust, persistent challenges, including political polarization, misinformation, and resource limitations, continue to hinder progress. Addressing these barriers through strategies such as community engagement and enhanced communication will be crucial for strengthening trust in public health and improving the effectiveness of future programs
Breaking Barriers to Smoking Cessation: Applying the Baby & Me - Tobacco Free Program to Improve Maternal and Child Health in Omaha, Nebraska
Smoking during pregnancy remains a pressing public health concern, contributing to adverse outcomes such as preterm birth, low birth weight, and developmental complications. In Nebraska, about 10% of pregnant women continue to smoke throughout pregnancy—above the national average, highlighting a critical gap in maternal health interventions. The Baby & Me – Tobacco Free (BMTF) program provides an evidence-based solution through structured counseling, carbon monoxide (CO) monitoring, and incentive-based rewards to support smoking cessation among pregnant women. This capstone project utilized the Getting to Outcomes framework to develop a detailed implementation plan to support Tobacco Free Nebraska (TFN) in launching the BMTF program in Omaha, Nebraska. A comprehensive needs assessment evaluated existing cessation resources, identified service gaps, and developed a logic model to guide program planning and align implementation efforts with desired outcomes. Key components of BMTF include monthly counseling sessions addressing socioeconomic and psychosocial barriers to quitting, CO monitoring to verify abstinence, and incentives—such as diaper vouchers—for participants who remain smoke-free. Guided by the Getting to Outcomes framework, this project outlines an implementation plan, while the CDC’s Program Evaluation Framework proposes an evaluation strategy. The program is expected to reduce smoking rates among pregnant women, improving maternal and child health outcomes and birth outcomes by reducing risks like low birth weight and preterm delivery. By addressing gaps in Nebraska\u27s public health resources, BMTF offers a scalable, replicable model for community-based smoking cessation interventions
Drivers and Mechanisms of Golgi Fragmentation as a Modulator of Disease
The Golgi apparatus plays a pivotal role in post-translational modification, trafficking, and secretion of proteins, ensuring proper cellular function. As a result, its fragmentation has been implicated in multiple pathological conditions, including alcohol-induced liver injury and prostate cancer (PCa). Despite its known impact on cellular homeostasis, the molecular mechanisms governing Golgi fragmentation remain to be clarified. Additionally, we have only just begun to understand the vast consequences of Golgi disorganization on disease progression.
This dissertation investigates the drivers and mechanisms of Golgi fragmentation, with a focus on its role as a modulator of disease. Using both in vitro and in vivo models, I demonstrate that chronic alcohol exposure triggers Golgiphagy (a selective form of autophagy that degrades Golgi membranes) through downregulation of the Rab GTPase, Rab3D. The loss of Rab3D results in p230 extension and dissociation of NMIIB from the Golgi. Ultimately, NMIIB dissociation gives way for NMIIA to associate with the Golgi and promote autophagy of the Golgi membranes. This Golgi disorganization leads to endoplasmic reticulum (ER) stress by activating the activating transcription factor 6 (ATF6)-mediated unfolded protein response (UPR). Additionally, the glycosyltransferase MGAT3 loses Golgi localization, but its competitor MGAT5 remains. This results in abnormal integrin glycosylation and binding to Galectin-3, increasing cluster formation and retention on the plasma membrane (PM). In addition to MGAT5-mediated glycosylation, underglycosylated integrins arrive at the PM carrying high-Man glycans due to alternative trafficking. This non-canonical route bypasses the Golgi and depends on STIM1- and ORP5-mediated ER-PM contact sites, which are involved in relieving ER stress and maintaining Golgi architecture.
The findings presented in this dissertation underscore a novel link between Golgi fragmentation, ER stress, and alternative protein trafficking routes, revealing how these pathways contribute to disease pathogenesis. I demonstrate that Golgi integrity can be restored by autophagy inhibition with hydroxychloroquine (HCQ) and ER stress inhibition by ATF6 depletion. Importantly, by restoring compact Golgi morphology, I have reduced tumor growth and progression of alcohol-induced liver injury. These results highlight Golgi disorganization as both a driver of pathology and a potential therapeutic target, offering new insights into the development of interventions for alcohol-related liver disease and aggressive PCa
Recycling Infrastructure and its Benefits: A Literature Review of Economic and Community Impact
Lincoln currently relies on a recycling system with private haulers and limited recyclables collection sites. To increase recycling rates and waste diversion, this review focused on the economic benefits of implementing city-wide recycling, the costs of implementing that recycling program, and the economic effects of making no change to the recycling program. Subjects of job creation, landfill costs, and virgin materials are discussed, along with the analysis of the economic, environmental, and social costs of each recycling program scenario. By the end of this project, I have identified the best recycling program option for the City of Lincoln to implement from an economic value standpoint. Methods included a comprehensive literature review on different recycling programs, landfill costs, tipping fees, recycling rates, operational costs, and economic impacts. The City of Lincoln Waste Diversion team directly participated in this project, helping me understand Lincoln’s waste programs, landfill space, and economic status. This project will help the community stakeholders in the City of Lincoln become knowledgeable about the different recycling opportunities it could have and how feasible they are
Integrating Human and Animal Health in the STOP Spillover Outbreak Scenarios
OBJECTIVES: To generate and employ scenarios of sentinel human and animal outbreak cases in local contexts that integrate human and animal health interests and practices and facilitate outbreak risk management readiness.
METHODS: We conducted a scoping review of past outbreaks and the strengths and weaknesses of response efforts in USAID STOP Spillover program countries. This information and iterative query-and-response with country teams and local stakeholders led to curated outbreak scenarios emphasizing One Health human:animal interfaces at sub-national levels.
RESULTS: Two core scenarios were generated adapted to each of 4 countries’ pathogen priorities and workflows in Africa and Asia, anchoring on sub-national outbreak response triggered by either an animal or human health event. Country teams subsequently used these scenarios in a variety of local preparedness discussions and simulations. The process of creating outbreak scenarios encourages discussion and review of current country practices and procedures. Guideline documents and lessons learned do not necessarily reflect how workflows occur in outbreak response in countries at highest risk for spillover events.
CONCLUSIONS: Discussion-based engagement across One Health stakeholders can improve sub-national coordination, clarify guidelines and responsibilities, and provide a space for interagency cooperation through use of scenarios in tabletop and other exercises