University of Nebraska Medical Center
University of Nebraska Medical Center Research: DigitalCommons@UNMCNot a member yet
10909 research outputs found
Sort by
Development and Characterization of Non-Viral Delivery Systems for Pulmonary Delivery of Nucleic Acid Therapeutics
No full textThe development of non-viral delivery systems for pulmonary delivery of nucleic acid therapeutics is driven by the need for safer and more accessible approaches to treat lung diseases, while avoiding the systemic side effects and immune responses associated with viral vectors. Such systems encompass both non-invasive inhalation-based platforms, and systemically administered platforms designed to achieve localized lung delivery. These strategies aim to enable high drug concentrations at the site of action, rapid onset of therapeutic effect, and greater therapeutic efficacy than existing treatments. Designing effective pulmonary delivery systems requires precise optimization of particle properties—including size, morphology, surface characteristics, cell-specific targeting, and evasion of host defenses. Rigorous formulation development and characterization are essential to ensure the safety, stability, and therapeutic efficacy of these complex systems.
This dissertation focuses on the development of delivery platforms that enable lung-selective delivery of nucleic acid therapeutics through two distinct routes: (1) perfluorocarbon (PFC)-based RNA nanocapsules for inhaled administration of microRNA (miRNA) therapeutics, and (2) macrocyclic ionizable lipid–based lipid nanoparticles (LNPs) for intravenous administration of mRNA and gene-editing therapeutics.
The first part of the dissertation focuses on the development and characterization of inhalable PFC-based RNA nanocapsules for the selective delivery of miRNAs to metastatic lung tumors. These nanocapsules are stabilized by PAMD-C, a cholesterol-modified polymeric analog of the FDA-approved CXCR4 antagonist AMD3100 (plerixafor), which confers tumor-targeting capability by recognizing CXCR4-overexpressing cancer cells. The PFC nanocapsules demonstrated remarkable ability to evade immune cell-mediated clearance while achieving passive targeting to type II alveolar and bronchial epithelial cells. In an orthotopic lung metastasis model, a single aerosolized dose resulted in more than 60% of cancer cells internalizing the nanocapsules, with pulmonary retention lasting over 48 hours. The platform induced negligible cytokine release, thus enabling repeated dosing. Treatment with therapeutic miR-34a delivered via this platform suppressed metastatic outgrowth, enhanced anti-tumor immunity, and doubled median survival relative to control paclitaxel chemotherapy. Collectively, this platform addresses key biological barriers to inhalable RNA medicines - including mucus entrapment, immune clearance, navigating through heterogeneous lung tissue architecture - and provides a promising and translatable path for treating a broad range of lung diseases.
The second part of the dissertation focuses on the synthesis and pharmacological evaluation of a LNP library derived from ten cyclam-based ionizable lipids, incorporating three distinct linker chemotypes and varied hydrophobic tails. Unlike conventional LNPs that predominantly accumulate in the liver, all cyclam-based formulations demonstrated remarkable lung tropism following intravenous administration, with lead candidates exhibiting lung-to-liver delivery ratios exceeding 100-fold. The cyclam-based LNPs distinguish themselves from standard DLin-MC3-DMA formulations by exhibiting improved safety profile, as they achieve lung-selective delivery without the need for cationic lipids like DOTAP, thereby circumventing lung thrombosis and other toxicities. Lipids incorporating benzylmethyl carbonate (BMC) linkers produced LNPs with compact sizes, higher RNA encapsulation efficiency, greater RNA recovery, and superior lung transfection potency compared to other linker types. In Ai9 reporter mice, two intravenous doses of Cre mRNA formulated with the lead cyclam lipid achieved ~30% lung-specific gene editing with minimal off-organ activity. Structure-activity analyses revealed that increased lipophilicity and aromatic content were inversely correlated with particle size and positively correlated with encapsulation efficiency. These findings establish design rules for macrocycle-guided delivery and provide a rational framework for engineering next-generation LNPs optimized for pulmonary gene therapy
Linking Training to Confidence: A Literature Review on Advancing Nutrition Environments in Child Care Programs
No full textThis comprehensive literature review examined child care nutrition training interventions using the Health Belief Model (HBM) to understand how to increase providers’ ability to serve nutritious food. By analyzing HBM constructs such as perceived severity, benefits, and barriers, the review assessed how training influences provider abilities and identified barriers and facilitators to consistently offering healthy meals and snacks. Studies were 1) published in English; 2) research conducted in the United States; 3) population involved home-based or center-based child care providers caring for children from birth to age 5; 4) articles published from January 1, 2015, to October 5, 2025; 5) training as a central part of the study; and 6) articles published in peer-reviewed journals. The final selection included 20 peer-reviewed articles published in English, all of which examined providers in the United States. Findings emphasized opportunities to enhance business practices, address common barriers, and tailor support to provider needs. Twelve studies demonstrated a direct impact of training and highlighted the importance of ongoing technical assistance in adopting nutrition practices. To maximize impact, public health leaders should customize interventions for both home-based and center-based providers. States and territories can further promote consistency by aligning Child and Adult Care Food Program standards, licensing regulations, and quality benchmarks
Ambient Air Pollution and Survival among Black Women with Epithelial Ovarian Cancer across Diverse Geographical Regions of the United States
No full textBackground: Ovarian cancer is a leading cause of gynecologic cancer mortality, with Black women experiencing 5-year survival rates of only 41%. Disproportionate air pollution exposure may impact survival. We evaluated associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) exposure with survival among Black women with epithelial ovarian cancer using data from the California Cancer Registry (CCR, n = 540) and the multi-state African American Cancer Epidemiology Study (AACES, n = 766).
Methods: Annual PM2.5 and NO2 levels were estimated at a 1 km resolution using well-validated ensemble-based prediction models derived from the Socioeconomic Data and Application Center and assigned to the participants\u27 residential addresses per their year of diagnosis (2004-2016). Weibull accelerated failure time models with participant-level frailty were used to assess air pollutant exposure associations with overall survival.
Results: Average PM2.5 and NO2 exposures were 11.3 μg/m³ and 25.8 ppb in CCR and 9.7 μg/m³ and 17.5 ppb in AACES. There was little evidence of an association between air pollution exposures and survival, with event time ratios (\u3e 1 indicate longer survival) in CCR of 1.08 (95% CI = 0.97, 1.20) per 1 μg/m³ PM2.5 and 1.07 (95% CI = 0.99, 1.15) per 10 ppb NO2, and in AACES of 1.00 (95% CI = 0.93, 1.07) per 1 μg/m³ PM2.5 and 1.04 (95% CI = 0.91, 1.19) per 10 ppb NO2.
Conclusions: Findings were modest and consistent across both cohorts and sensitivity analyses, supported by the use of advanced exposure modeling. Future research should use time-varying, long-term exposure data and examine interactions with occupation, physical activity, and neighborhood stressors
Multimodal Longitudinal Assessment of the Developmental Trajectory of Resting State Connectivity and Neural Oscillatory Dynamics Supporting Executive Function
No full textPsychiatric disorders are the most prevalent debilitating illnesses across the lifespan. Importantly, epidemiologic studies indicate that 75% of all diagnosable psychiatric disorders begin prior to age 24, highlighting the need for investigations of the developing brain. A critical mission of developmental cognitive neuroscience is to characterize normative developmental trajectories of neural physiology, alongside the adoption of dimensional models to mitigate longstanding categorical representations of neurotypical and atypical (i.e., psychiatric diagnoses) development. This dissertation harnesses the complementary strengths of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to better characterize longitudinal trajectories of neurodevelopment. Specifically, in Chapter 1 we identified the relationship between subclinical levels of trauma-related symptomatology and longitudinal trajectories of resting-state fMRI connectivity, highlighting the importance of investigations across subclinical levels of symptomatology in normative samples, prior to achieving diagnostic levels. In Chapter 2, we identify relationships between a biological measure of age (i.e., pubertal timing) and longitudinal changes in neural oscillatory dynamics supporting executive function, above and beyond the effects of chronological age. Finally, in Chapter 3 we assess sexually dimorphic relationships between salivary testosterone measures and trajectories of oscillatory activity in brain regions that are critical for executive function. Overall, these novel results enhance the characterization of neurodevelopmental trajectories and may enhance future diagnosis, prognosis, and monitoring of mental health disorders that emerge during childhood and adolescence
Disability as both a Source of Marginalization and a Tool for Agency In the Work of William Shakespeare
Get PDFThis program is presented in conjunction with the exhibition “’And there’s the humor of it!’ Shakespeare and the Four Humors,” created by the National Library of Medicine and on display at McGoogan Library (Level 6) through March 15. An online exhibition is also available.
Historically disability is ignored or absent in literature, art, culture, and media. While limited, representation of disability has been critiqued for perpetuating both inaccurate and demeaning stereotypes, leading to prejudice and discrimination against the disability community. William Shakespeare’s works often reflect the complex attitudes toward disability present in early Modern England. While not explicitly defined by Shakespeare, his works explore disability through a variety of characters and themes, reflecting both the prejudices and attitudes toward disabled people during this time.
During this program, Davi Kallman, PhD will review the two most prominent and modern models of disability (medical and social models) and will discuss how Shakespeare’s work has influenced the creation of both these widely accepted models.
Additionally, she will discuss how Shakespeare’s plays contain references to disabilities and non-normative bodies. This includes a review of these common themes addressed by disability and media scholars in William Shakespeare’s work: Disability as a Marker of Character Empathy and Humanity of Disability Social Stigma and Marginalization of Disability Disability as a Source of Power or Agency
Lastly, she will reflect on how Shakespeare’s treatment of disability is multifaceted, blending prejudices of his era with moments of insight and empathy toward the disabled community. While his works do not advocate for progressive understanding of disability by modern standards, they offer nuanced portrayals that ask us to reflect on our own understanding of the social and personal implications of non-normative minds and bodies.
About Dr. Davi Kallman
Davi Kallman, PhD is a Mexican, Jewish, Disabled Woman whose intersecting identities amplify her advocacy for traditionally marginalized communities. She is a published author, an award-winning speaker, and a powerful institutional change-maker.
Dr. Davi Kallman is the District Dean of Student Engagement at Pierce College in Lakewood Washington. Kallman also serves as Pierce College’s 504/ADA Coordinator. In this role she works with Pierce College District students, faculty, and staff to ensure that student disability rights are upheld. In her spare time, she serves as an adjunct Professor of Communication at Tacoma Community College (TCC).
She earned her PhD in Health Communication from the Edward R. Murrow College of Communication at Washington State University, following her master’s and bachelor’s degrees in communication from the University of Texas at El Paso (UTEP). Dr. Kallman leverages her expertise in media literacy and other interventions to dismantle stereotypes in institutional settings, fostering environments that are more inclusive and equitable.
A key part of her journey has been informed by her own experiences as a dyslexic individual. Her work reflects her commitment to ensuring that individuals with disabilities—both visible and “hidden”—receive the support they need to thrive. Dr. Kallman’s experiences inform her vision for a more inclusive and accessible higher education system.https://digitalcommons.unmc.edu/mcgoogan_lectures/1012/thumbnail.jp
Multilevel Considerations for Youth Attention-Deficit/Hyperactivity Disorder Prognosis and Management: Examining the Relationship between Health Care Factors and Familial Factors in Families of Children and Adolescents with ADHD
No full textAttention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder impacting up to 10% of U.S. youth, and is associated with several negative social, health, and academic or occupational outcomes. Risk and prognostic factors for ADHD are multifactorial, and the management of youth ADHD is multimodal. Familial environments are one prognostic factor for ADHD, with family resilience being positively associated with youth ADHD prognosis. Researchers exploring multilevel interventions for the management of youth ADHD have proposed health care systems as a setting for interventions targeting family resilience, however little research examines the relationship between health care system factors and family factors in families of children and adolescents with ADHD. The studies in this dissertation examine the relationship between three health care system factors, including family-centered care, care coordination, and parental emotional support from a health care provider, and family resilience, using the Family Resilience and Connection Index (FRCI) as an outcome measure. Outcomes demonstrate a statistically significant relationship between family-centered care and FRCI, as well as care coordination and FRCI. There was not a statistically significant relationship between parental emotional support from a health care provider and FRCI. As models of care for youth with ADHD, such as the Medical Home Model, include multiple health care system factors, future research should examine the comparative and/or cumulative impacts these health care system factors have on family resilience to better inform health care system practices in the management of children and adolescents with ADHD
Improving Information Literacy and Research Skill Instruction Through Peer Consultation
Get PDFThe team at McGoogan Health Sciences Library at the University of Nebraska Medical Center utilized Design Thinking methodology to improve instructional training of library faculty. The Education & Research Services team developed a 5-step peer consultation process to standardize how feedback on instruction is solicited and given. The instigation of this process has led to increased discussions on instructional pedagogies and assessment of instruction, collaboration, and instructional innovation across multiple departments within the library. The process has been adapted to provide feedback in multiple contexts, led to the standardization of certain aspects of instructional design, and has assisted with the onboarding of new faculty. The peer consultation process, once incorporated into policy and procedure, leads teams to develop a culture of trust and collegial collaboration in the improvement of instruction and library services
Translating Knowledge of Functional Cognition into Occupational Therapy Practice
Get PDFFunctional cognition is a critical component for safely and effectively performing daily occupations. Occupational therapy (OT) practitioners are uniquely positioned and trained to address functional cognition while considering a client’s abilities and environments. A multimedia e-learning module was developed as a teaching modality to enhance understanding and application of functional cognition concepts for OT students and practitioners. As educators, it is important to assess the effectiveness of the teaching and learning experiences we create. We evaluated the multimedia e-learning module for quality, value, and usefulness using critical reflection perspectives. These perspectives included a literature review, as well as from learner, educator, and module developer user groups. These perspectives included a literature review, as well as from learner, educator, and module developer user groups. User groups rated the module using the Nebraska E-learning Scorecard and a modified version of Brookfield’s Critical Incident Questionnaire. Results indicate this e-learning module is a worthwhile teaching and learning tool for functional cognition across all perspectives. Overall, the module was found valuable compared to traditional learning methods. This study contributes to the OT education literature by demonstrating the effectiveness of multimedia e-learning in teaching functional cognition. The findings can inform the development of future e-learning modules within OT and other healthcare disciplines. We explain how the knowledge to action framework guided our translational science practice for the module’s creation, evaluation, and use. This multimedia e-learning module serves as a valuable resource for learners and practitioners, addressing a critical gap in OT education related to functional cognition
Medical Impact of the College World Series on the Omaha Community
Get PDFhttps://digitalcommons.unmc.edu/emet_posters/1043/thumbnail.jp
The Impact of Stigma on Individuals Affected by Leprosy: A Pilot Study
Get PDFBackground: Leprosy, while a treatable condition, continues to be associated with significant stigma, which adversely influences the physical, psychological, social, and economic well-being of affected individuals throughout their lives. The stigma linked to leprosy leads to social exclusion, mental health difficulties, and obstacles to accessing healthcare and employment opportunities (Brakel et al., 2019; Sermrittirong & Van Brakel, 2014). This research employs Life Course Theory to describe the long-term experiences of stigma, coping strategies, and social support individuals living with leprosy. By synthesizing findings from existing literature and conducting a qualitative interview, the study offers an in-depth understanding of how various life stages and social environments shape the experiences of stigma associated with leprosy.
The Public Health Triad (agent, host, and environment) is a critical framework for understanding the interplay of biological, individual, and environmental factors contributing to stigma and its management. In the context of leprosy, the agent Mycobacterium leprae not only causes physical manifestations of the disease but perpetuates societal misconceptions and fear due to its historical associations. The host, representing individuals affected by leprosy, often endures psychosocial challenges compounded by these misconceptions (Bassey, 2012). Finally, the environment, shaped by cultural, economic, and healthcare infrastructures, influences the severity and persistence of stigma. For instance, in Africa, traditional beliefs and fears exacerbate stigma, whereas in the United States, a lack of awareness about leprosy reinforces ignorance and prejudice. It\u27s important to note that the unique cultural contexts in different regions present distinct challenges for individuals affected by leprosy, highlighting the need for culturally sensitive interventions. Addressing these dimensions collectively can inform more effective stigma-reduction strategies.
Methodology: This study employs a triangulated research design, which integrates a comprehensive literature review with an interview with an individual affected by leprosy. The literature search was carried out using databases such as PubMed, PsycINFO, and Embase, with specific inclusion criteria targeting studies on leprosy stigma, coping strategies, and social support networks. Meanwhile, the interview provided valuable personal and professional perspectives on the experience of stigma across various life stages. The analysis was guided by Life Course Theory, facilitating an exploration of how factors such as the timing of diagnosis, the evolution of social relationships, and cumulative stigma-related experiences influence coping strategies and resilience over time (Bryman, 2016; Creswell, et al., 2016).
Findings: The interview and literature review results reveal the enduring stigma associated with leprosy and its significant social, psychological, and economic ramifications. The interview provided insights into the participant\u27s experiences, which included delayed diagnosis, societal judgment, self-imposed isolation, and dependence on religious coping mechanisms. Similarly, the literature highlights how stigma results in social exclusion, courtesy stigma experienced by caregivers, and the perpetuation of misconceptions about the disease. Both the interview and the literature stress the necessity for comprehensive mental health support, which should be a key component of any intervention strategy. This support is crucial in alleviating the psychological effects of stigma and enhancing the quality of life for those affected. The Life Course theory perspective further elucidated how stigma can impact crucial life transitions, including education and employment, ultimately influencing long-term mental health outcomes and resilience (Chatters, 2014).
Conclusion: This research demonstrates that Life Course Theory provides significant insights into the persistent impact of leprosy stigma throughout various life stages, thereby informing the creation of culturally appropriate interventions and public health strategies. Mitigating stigma necessitates the education of both communities and healthcare professionals, the establishment of support networks, and the empowerment of individuals affected by leprosy to more effectively navigate social transitions. Subsequent investigations should focus on the long-term psychological effects of stigma and evaluate the efficacy of community-based interventions across different cultural settings (Sottie & Darkey, 2019). By integrating a literature review and an interview, this study emphasizes the critical need for holistic strategies to diminish the stigma surrounding leprosy. It supports formulating actionable strategies to enhance the quality of life for affected individuals.
Integrating Life Course Theory into the Results underscores the critical role of timing, social relationships, cumulative impacts, and societal attitudes in shaping the stigma experienced by individuals with leprosy. For example, delayed diagnosis during formative years disrupts educational and social development, while cumulative stigma impacts long-term psychological resilience. The Public Health Triad also provides a structured lens to examine how biological, individual, and environmental factors interact to perpetuate stigma and its consequences. Both frameworks collectively elucidate how individuals navigate the challenges of stigma across life stages, emphasizing the importance of timely and culturally sensitive interventions