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A Stakeholder Analysis for Engagement: a PESTLE Framework for the Nebraska Coalition for Patient Safety
Get PDFThe Nebraska Coalition for Patient Safety (NCPS) is a not-for-profit organization designed to collaborate with Nebraska’s hospitals and healthcare organizations to benefit patient safety. NCPS, as do all organizations, have varying types of stakeholders who are engaged at some level in the function of NCPS or the services of NCPS. Research across industries demonstrates the importance of stakeholder assessment and evaluation and it has been shown that collaborative efforts with stakeholders can improve outcomes (Newig et al., 2023). Acquiring input from those who are directly affected by the organization’s strategic planning can help determine and shape future direction. This capstone project provided NCPS with a stakeholder analysis that is intended to offer guidance in its future strategic planning and communication efforts. The completed analysis used aspects of the validated PESTLE method, which organized information and sought input from stakeholders around Political, Economic, Social, Technological, Legal, and Environmental categories. Stakeholders were applied to a power-interest matrix, and a SWOT analysis of internal perspectives from NCPS relating to the PESTLE categories was completed. A survey was developed and administered to stakeholders on their expectations and directional input for NCPS. A report was developed from the survey analysis to inform NCPS if their efforts satisfy stakeholders’ desires for data management, educational offerings, and organizational priorities. The analysis revealed that NCPS is valued as an investment and seen as an important means of advocacy. However, some stakeholders reported a disinterest in employee engagement with patient safety programs. Active services of NCPS are underutilized and lead to a lack of reporting. The tools provided by this project will help guide NCPS on future goals to address concerns
Surge Scramble: An Evaluation of Combining the Medical Response and Surge Exercise with the Centers for Disease Control and Prevention’s Pan Flu Scramble
No full textThis report analyzes how Hospital Preparedness Program funding recipients in Nebraska adapted the Center for Disease Control’s Pan Flu Scramble format to meet Medical Response and Surge Exercise (MRSE) requirements in the 2023-2024 fiscal year. By combining the MRSE and Pan Flu Scramble, the recipients created an in-person functional exercise format for the six Nebraska health care coalitions to test their respective chemical plans and the Health Care Crisis Protocol for the State of Nebraska. The report explains the design and conduct of the exercises and provides a comprehensive evaluation of the exercise design and conduct. This report will outline the methods, tools, and lessons learned to support the use of Surge Scrambles in other states to help meet the annual MRSE requirement
Multi-Modal MRI for the Pre-Clinical Evaluation of HIV-Linked Changes in the Central Nervous System
Get PDFThough the inception of anti-retroviral therapy (ART) has fundamentally changed the life expectancy of human immunodeficiency virus (HIV) patients, accessibility and outcomes vary enormously along demographic lines. Even for people living with HIV (PLWH) with perfect access and adherence to anti-retroviral drugs (ARVs), modern treatment plans are fundamentally unable to secure complete viral remission for patients. The cause of this perpetual infection is the persistence of viral reservoirs in the central nervous system (CNS), hidden beyond the reach of modern ARVs, leaving patients to deal with lifelong medication side-effects and risks of developing HIV-associated neurodegenerative disorders (HAND). Despite improving outcomes in many nations, a lack of understanding of HAND and ARV efficacy causes a significant decline in the quality of life for PLWH. Fortunately, the utilization of the chemical exchange saturation transfer (CEST) effect as a novel contrast method for magnetic resonance imaging (MRI) offers complementary utility to mature methods leveraging water diffusion and metabolic spectroscopy. The power of multi-modal MRI allows for robust, non-invasive assessment of neuroimmune health and drug biodistribution in HIV mouse models through endogenous contrast agents alone. This thesis investigates the intersection of multi-modal magnetic resonance imaging and HIV theranostics, in hopes of accelerating the development of effective and accessible immunological care
Development and Evaluation of the Cystiene Cathepsin Trapping Approach Incorporated in NTSR1- and FAP-Targeted Radiotherapeutics
No full textFibroblast activation protein (FAP) and neurotensin receptor subtype 1 (NTSR1) are highly expressed in multiple malignancies, making them promising targets for radiopharmaceutical therapy. FAP is a membrane-bound serine protease predominantly expressed in cancer-associated fibroblasts within the tumor stroma of over 90% of epithelial cancers. Its restricted expression in normal adult tissues makes it an ideal candidate for targeted radionuclide therapy. However, existing FAP-targeted agents, such as 177Lu-FAPI-46, exhibit rapid tumor washout, limiting their potential for sustained radiation dose delivery. Similarly, NTSR1, a G-protein-coupled receptor overexpressed in pancreatic, colorectal, and prostate cancers, has been explored as a radiopharmaceutical target. Although peptide-based 177Lu-3BP-227 has shown clinical feasibility, its limited tumor retention has hindered therapeutic efficacy.
To address these challenges, we developed 177Lu-FAPI-ET1 and 177Lu-NA-ET1, two novel radiopharmaceuticals incorporating a cysteine cathepsin trapping agent designed to prolong tumor retention via endolysosomal trapping. This strategy utilizes an epoxysuccinyl peptide inhibitor that selectively and irreversibly binds to the catalytic cysteine residue of endolysosomal cysteine cathepsins, forming stable high-molecular-weight adducts. Since cysteine cathepsins are highly expressed in the tumor microenvironment and play a role in extracellular matrix remodeling and cancer progression, leveraging their proteolytic activity for intracellular trapping enhances the retention of radiopharmaceutical constructs within tumor cells.
In vitro studies confirmed that both constructs maintained high binding affinity to their respective targets and efficiently formed covalent adducts with cysteine cathepsins. Biodistribution studies in glioblastoma cancer xenograft models demonstrated significantly prolonged tumor retention, with 177Lu-FAPI-ET1 showing a five-fold increase in tumor residence at 168 hours post-injection compared to 177Lu-FAPI-46. Similarly, 177Lu-NA-ET1 displayed 1.9- to 4.4-fold enhanced tumor retention relative to 177Lu-3BP-227 across multiple cancer models. Human radiation dosimetry estimates indicated that these modifications improve the therapeutic index while maintaining tolerability.
These findings validate the endolysosomal trapping approach as an effective strategy to overcome rapid clearance in small-molecule targeted radiopharmaceuticals. By leveraging cysteine cathepsins to facilitate intracellular trapping, this approach significantly enhances tumor retention and radiation dose delivery. Future work will focus on optimizing specificity to minimize off-target effects, but this strategy holds substantial promise for advancing precision radiopharmaceutical therapy in FAP- and NTSR1-expressing malignancies
Optimizing Geranylgeranyl Diphosphate Synthase Inhibitor (GGSI) Therapy for Multiple Myeloma
Get PDFMultiple myeloma (MM) remains an incurable cancer despite significant therapeutic advances, constituting roughly 13% of all blood cancers. It is characterized by accumulation and proliferation of plasma cells in the bone marrow. Currently available potent anti-myeloma drugs have several limitations, including off-target toxicity and poor physiochemical properties. This dissertation focuses on optimizing geranylgeranyl diphosphate synthase inhibitor (GGSI) therapy, which targets geranylgeranyl diphosphate synthase (GGDPS) in the isoprenoid biosynthetic pathway, using polymer-drug conjugates and combination therapy strategies. Several triazole bisphosphonate-based GGSIs have demonstrated metabolic stability and anti-tumor activity in myeloma xenograft models, but hepatotoxicity limits the therapeutic potential. To overcome this, we have developed and optimized PEGylated GGSI and hyaluronic acid-drug conjugates to enhance circulation and improve targeting to MM cells. Various parameters, including PEG or HA chain length, activation agents, and reaction conditions, have been optimized to create polymer-drug conjugates that has potential to improve drug circulation and targetability while reducing liver uptake and associated toxicity.
Recognizing the potential of combination therapy in MM, targeting isoprenoid biosynthetic pathway and fatty acid synthesis pathway could be beneficial, given their impact on MM proliferation. GGDPS plays a pivotal role in isoprenoid biosynthetic pathway that helps in Rab-mediated protein trafficking. Similarly, fatty acid synthase (FASN) is a key enzyme involved in neoplastic lipogenesis and may be associated with tumor growth and survival. Cytotoxicity assays revealed synergistic or additive effects in MM cell lines and enhanced induction of apoptosis was also observed following combination treatment. When effects on energy metabolism were evaluated, the combination therapy inhibited mitochondrial function more effectively than either drug alone. Metabolomics studies utilizing an LC-MS/MS methodology revealed alteration of several key metabolic pathways due to combination therapy. Preliminary in vivo studies confirmed the safety and feasibility of combination therapy with RAM2061 and cerulenin administered to CD-1 mice. In aggregate, these data provide rationale for further studies exploring combination therapy with GGSI and FASN inhibitor for the treatment of M
Evaluating Clinical Competency in Undergraduate Nursing Students: A Mixed Methods Study
No full textClinical evaluation tools play a crucial role in assessing nursing students\u27 competencies, ensuring they develop the necessary knowledge, skills, and attitudes required for safe patient care. Current clinical evaluation tools (CETs) are seen as subjective, with ambiguous evaluation language, leading faculty to rely on personal factors for their evaluation standards and causing students to feel a sense of bias in the evaluation process. The overall purpose of this dissertation was to gain a deeper understanding of competency-based CETs and how a student is assessed as having achieved clinical competency. This was initially accomplished by conducting an integrative review to assess currently used CETs, focusing on the inclusion of psychometric analysis. Next, a comparison and contrast of the concepts of competency and competence was completed using a concept analysis approach, examining the concepts’ interconnectedness. Finally, an inductive, thematic mixed methods study was conducted to determine the psychometric analysis of an adapted CET, along with faculty interviews to foster a deeper understanding of decision-making associated with student clinical competency achievement. The major findings from the integrative review indicated inconsistencies in all aspects of clinical evaluation, such as what is competency vs. competence, which competencies to evaluate, who should complete the CET, how often a student should be evaluated, and which psychometric properties should be assessed. The comparison of the concepts of competency and competence provided clear delineations of these concepts, highlighting their deeply intertwined nature. Major findings from this iv dissertation\u27s psychometric analysis revealed positive inter-rater reliability; however, the statistics were limited due to the researcher\u27s decision to maintain the original format of the CET. From the interviews with faculty, four themes impacting their decision-making were identified: 1) utilization of guidelines, 2) personal experiences and expectations, 3) prevention of biases, and 4) uncertainty. This dissertation has implications for future research and educational practice. Understanding the factors faculty use to determine student clinical competency plays a key role in the development and adaptation of CETs. Further research is needed to develop and implement the adapted CET and to understand the phenomenon of decision-making associated with student clinical competency achievement
A Research Report: What Are the Challenges That Refugee Women Experience When Seeking Healthcare Related to Pregnancy in the United States?
Get PDFBackground
Refugees in the United States, including African refugee women, face many challenges in seeking healthcare after moving to the United States to resettle. It is urgent and essential to look into some of the health challenges the refugee community faces here in Omaha, Nebraska, that prevent them from seeking healthcare, especially when pregnant. This Capstone research project aims to focus on African refugee women, specifically in Omaha, Nebraska, and the challenges they face seeking healthcare related to pregnancy.
Methods
This research report involved five in-depth interviews conducted over Zoom. The target population was refugee mothers who had given birth in the United States in the past 2-3 years. I recruited participants from the Promo Care program within the African Immigrant Family Services Organization in Omaha, Nebraska. I then coded the interview data and categorized it into themes.
Results
Data from the five in-depth interviews revealed African refugee beliefs, behaviors, and challenges the women face when seeking healthcare related to pregnancy. Most pregnant African refugee women believe in seeking prenatal care when they first find out they are pregnant, while others are still reluctant to seek care. In-depth interviews with African refugee women revealed several challenges, including difficulties with accessing Health insurance, navigating the healthcare system, and securing transportation.
Conclusion
Notably, pregnant African refugee women face numerous challenges in Omaha, Nebraska, and the United States as a whole when seeking healthcare, and a lot still has to be done on the State and national level to close the health disparity gap between these vulnerable groups
ST6GalNAc-I regulates tumor cell sialylation via NECTIN2/MUC5AC-Mediated Immunosuppression and Angiogenesis in Non-Small Cell Lung Cancer
Get PDFGlycosylation controls immune evasion, tumor progression, and metastasis. However, how tumor cell sialylation regulates immune evasion remains poorly characterized. ST6GalNAc-I, a sialyltransferase that conjugates sialic acid to the glycans in glycoproteins, was overexpressed in an aggressive-type KPA (KrasG12D/+ Trp53R172H/+ Ad-Cre) lung adenocarcinoma (LUAD) model and patient samples. Proteomic and biochemical analysis indicated that ST6GalNAc-I mediated NECTIN2 sialylation in LUAD cells. ST6GalNAc-I-deficient tumor cells cocultured with T cells were more susceptible to T cell-mediated tumor cell killing, indicating a key role for NECTIN2 in T cell dysfunction. Mice injected with St6galnac-I-knockdown syngeneic cells showed reduced lung tumor incidence and Nectin2/Tigit-associated immunosuppression. ST6GalNAc-I-deficient cells exhibited reduced P-DMEA metabolite levels, while administration of P-DMEA promoted LUAD cell proliferation via MUC5AC. MUC5AC interacted and colocalized with PRRC1 in the Golgi, suggesting a potential role for PRRC1 in MUC5AC glycosylation. Mice injected with ST6GalNAc-I/MUC5AC-deficient cells (human LUAD) exhibited reduced lung tumor incidence, angiogenesis, and liver metastases. Mechanistically, ST6GalNAc-I/MUC5AC regulates VCAN-V1, a key factor in tumor matrix remodeling during angiogenesis and metastasis. These findings demonstrate that ST6GalNAc-I-mediated sialylation of NECTIN2/MUC5AC is critical for immune evasion and tumor angiogenesis. Targeting this pathway may prevent LUAD development and/or metastasis