University of Nebraska Medical Center

University of Nebraska Medical Center Research: DigitalCommons@UNMC
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    10909 research outputs found

    Stranger\u27s Hands

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    Flexor Digitorum Profundus, Edge of Tomorrow and Holy Sepulchre Circle of Life

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    Invisible

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    Asphyxiation by hanging, intentional self-harm, initial encounter (ICD-10: T71.162A)

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    After the Storm

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    SARS-CoV-2 Genomic Surveillance Using Self-Collected Saliva Specimens during Occupational Testing Programs

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    Continually emerging SARS-CoV-2 variants pose challenges to clinical and public health interventions, necessitating sustainable approaches to real-time variant monitoring. This case study describes an innovative SARS-CoV-2 screening and surveillance program that demonstrates the utility of sequencing-based variant monitoring using self-collected saliva specimens. We conducted saliva-based SARS-CoV-2 screening in occupational settings in Omaha, Nebraska from December 2021 through November 2022. 8,372 saliva specimens collected from 1,480 participants were tested for SARS-CoV-2 RNA by extraction-free PCR, with 334 positive samples referred for whole-genome sequencing analysis. Program utilization, quality metrics, and sequencing outputs were compared across sites. Specimen quality was high across program settings, demonstrating the suitability of self-collected saliva specimens for PCR and genomic surveillance testing. Virus RNA sequencing successfully determined the variant strain in 83 and 67% of SARS-CoV-2-positive saliva samples collected in two program settings, demonstrating the successful integration of SARS-CoV-2 sequencing for variant determination into screening programs in occupational settings using self-collected saliva with an extraction-free qRT-PCR testing method. We further demonstrate that the sensitivity and efficiency of variant analysis is dependent on the PCR cycle threshold (Ct) cutoff of the diagnostic assay virus gene target. Use of an optimized Ct value cutoff for sequencing referral is recommended. Community-based saliva testing programs can be utilized to enhance variant monitoring, and could be considered in the risk identification of other respiratory infections. This approach offers the advantages of a non-invasive specimen collection, no need for supervised collection by a healthcare worker, supply chain resiliency, distributable access, and scalability

    Building Our Own Bridge: Paving the Way to New Promotion and Tenure Guidelines

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    Our academic health sciences library worked to construct a P&T document that fairly represented all areas of our library: education/research, collections, systems/technology, and special collections. This presentation highlights the process our library took to construct this new document and how these guidelines will be used for P&T and annual reviews. Background: When it came to the Promotion & Tenure (P&T) process, our health sciences library had a short supplementary criteria document that provided some guidance on the P&T process and examples of the three areas of teaching, research, and service. Past candidates applying for promotion and tenure relied on the University’s general P&T documentation. Faculty librarians faced challenges describing their work within the general university guidelines. With feedback from faculty who have recently gone through the P&T process, library administration tasked a committee to redraft the library’s P&T guidelines. Description: To help us understand how health science library faculty are evaluated, the Promotion & Tenure (P&T) committee gathered and reviewed peer institutions’ promotion and tenure guidelines. In addition, we reviewed other college guidelines within our institution and the current library P&T criteria document. The goal of this review was to create our own in-depth guidelines that, in the future, library faculty must utilize through all stages of their P&T journey. Some of the reviewed promotion and tenure documents grouped promotion criteria into the categories of librarianship, research, and service, but our team felt that limiting librarianship to a single aspect of our promotion criteria would miss or de-emphasize the importance of some aspects of our work as librarians. Program Conclusion: The new document focuses on 1) education, 2) research and creative activities, and 3) service and administration. To make sure that the P&T document fairly represented all areas of our library (education/research, collections, systems/technology, and special collections), we encouraged faculty to interact with the document to ask questions and offer additional suggestions. After three rounds of faculty review between November 2024 and January 2025, the document received a vote of approval in February 2025 and was submitted to University Academic Affairs and the Board of Regents. The proposed P&T guidelines were used as a blueprint for a faculty workload document that had been requested by Academic Affairs and will, after their approval, inform faculty members’ annual reviews

    Identification of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (ARS)

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    Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro with 4-8 Gy and in vivo by exposing Mus musculus to 7.3 Gy of whole-body irradiation. The primary endpoints of this study include cellular viability, DNA damage via γ-H2AX, colony formation, and overall survival at 30-days post-irradiation. In addition to evaluating the radioprotective performance of each compound, this study establishes a distinct set of in vitro assays to predict the overall efficacy of potential radioprotectors in an in vivo model of ARS. Furthermore, these results highlight the need for FDA-approved medical intervention to protect against ARS

    Evaluation of a Joint Staffing Model with Clinical Pharmacy in an Outpatient Family Medicine Residency Clinic

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    https://digitalcommons.unmc.edu/com_fam_pres/1028/thumbnail.jp

    Study of Peptide Amphiphiles as Antimicrobial Agents

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    The global antimicrobial resistance (AMR) crisis presents a severe public health threat, with drug-resistant infections now the third leading cause of mortality worldwide. This escalating problem, driven by the rapid proliferation of multidrug-resistant organisms (MDROs) like the ESKAPE pathogens, severely limits treatment options and imposes substantial economic burdens. The crisis is further exacerbated by a limited pipeline of new antimicrobial agents, as most recently approved drugs are modifications of existing classes rather than novel compounds. Peptide amphiphiles (PAs) offer a promising alternative due to their membrane-targeting mechanism, which reduces the likelihood of resistance development. These molecules are amphiphilic and positively charged, allowing them to interact with and disrupt microbial cell membranes. This non-specific, physical disruption makes it significantly harder for bacteria to evolve resistance compared to conventional antibiotics. Beyond direct killing, PAs can also disrupt bacterial biofilms. Chapter 2 detailed a comprehensive structure-activity relationship (SAR) study of 33 PAs, elucidating the physicochemical properties governing their antimicrobial efficacy and specificity. PCA revealed that zeta potential was critical for Gram-positive MRSA JE2, while hydrophobicity (LogP) was more important for Gram-negative E. coli K12 and P. aeruginosa; for A. baumannii, both factors were equally crucial. PAs forming fibrous nanostructures exhibited lower activity compared to spherical micelles, due to strong intermolecular cohesion. Mechanistic studies confirmed PA-induced membrane permeability and depolarization, leading to visible structural damage. In vitro cytotoxicity and in vivo studies in Galleria mellonella showed promising profiles for selected PAs. Chapter 3 explored the additive effect of PA 25 in combination with naphthylthiazole 1-81 against MRSA JE2. The 16:1 ratio (PA 25:1-81) showed an additive effect, suggesting PA-mediated membrane disruption facilitated 1-81\u27s entry. The combination demonstrated significant anti-biofilm activity, inhibiting formation and disrupting mature biofilms. Gene expression analysis indicated modulation of key virulence and biofilm-related genes (e.g., agrA, saeR, fib). A 21-day multi-passage resistance study showed low resistance induction. The combination significantly reduced in vitro hemolytic activity of PA 25. In vivo studies confirmed robust antimicrobial protection, comparable to or surpassing vancomycin. In conclusion, this thesis successfully demonstrated PAs as effective antimicrobial agents, individually and in combination, against resistant bacterial strains. The detailed SAR provided critical insights for rational design. The consistent membrane-disrupting mode of action reduces resistance development, a significant advantage in the AMR crisis. The synergistic potential of PAs with small molecules enhanced efficacy and improved the therapeutic index by reducing toxicity. Anti-biofilm activity and low resistance induction are particularly encouraging. Future work includes molecular dynamics simulations, target identification for small molecules, broader gene expression analysis, and optimizing design principles for species-specificity, aiming to accelerate clinical translation. In Chapter 4, the conclusion and future directions are described

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