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Healthcare Emergency Management Salary Survey Analysis
Full text linkThe field of emergency preparedness is an often unknown and unrecognized aspect of healthcare, forming an integral component of patient and worker safety. While an important field, there is limited data focused on the field pertaining to salaries of workers, resources utilized and produced, and the typical working environment. The purpose of this project is to assess salary and other demographic markers of healthcare emergency preparedness professionals in the United States. The project will compare salary, full-time equivalent levels, preparedness program budgets, and other markers across the country. The data from this study will also be compared to previous survey results, which gave preliminary findings, and the data that is available through the United States Bureau of Labor Statistics
Cholestasis and Fluid Flow are Biomechanic Regulators of Cholangiocarcinoma Progression
No full textCholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture conditions. Static culture caused Akt phosphorylation and activation, β-catenin nuclear translocation, and increased markers of epithelial-to-mesenchymal reprogramming activity. Static culture increased tumor cell migration that was consistent and independent of the direction of fluid flow. Static culture increased tumor cell proliferation. These studies utilized a phospho-protein sandwich-ELISA, immunoblots of whole cell lysates and of subcellular fractions from tumor cell lines, and a novel migration assay to test cholangiocarcinoma cell responsiveness to fluid shear stress. Stasis further activated signaling via FGF19 and its cognate receptor, FGFR4, that provided apoptosis resistance, motivated cell migration, and regulated cholangiocarcinoma tumor growth. FGF19 was secreted into the media by static cells, a possible mechanical regulation of FGF19 and stabilization of FGFR4 in regions of cholestasis. Pan-FGFR inhibition and FGFR4 inhibition increased TRAIL-induced tumor cell death and reduced proliferation. Preferential FGFR4 inhibition also enhanced TRAIL-induced cell death in combination with gemcitabine/cisplatin chemotherapy, the standard of treatment for this cancer. Initial therapeutic efficacy by targeting the FGF19/FGFR4 axis in an in vivo model of cholestatic cholangiocarcinoma led to tumor weight reduction. Together, these data demonstrated the regulation of cholangiocarcinoma by mechanical forces modeling cholestasis and acting through receptor tyrosine kinase receptor signaling, Akt, β-catenin, and a novel mechanical-kinase pathway. Restoring mechanosensory responses to patients with cholestatic tumors may renew interest in a therapeutic paradigm whereby bile flow is restored as an approach in cholangiocarcinoma to return cells toward a healthy biliary epithelium program
Niclosamide-Loaded Polyanhydride Nanoparticles to Combat Gemcitabine Resistance in Pancreatic Cancer
Full text linkPurpose
Pancreatic cancer (PC) is a highly lethal malignancy and lacks effective treatments. Current chemotherapies, including gemcitabine (Gem) in combination treatment regimens, produce dose-limiting toxicity, drug resistance, and ultimately limited improvement in the overall survival of PC patients. Niclosamide (Nic), a clinically safe FDA-approved anthelmintic drug has been shown to have anti-cancer properties; however, its limited bioavailability makes Nic largely ineffective as a therapeutic agent. To address this challenge, we have developed a novel combination therapy of Gem with the repurposed drug, Nic, loaded in biodegradable polyanhydride nanoparticles (NicNp), as an effective treatment option for PC. Methods
We synthesized and characterized NicNp in vitro and evaluated their biodistribution and efficacy in xenograft and syngeneic pancreatic tumor models in mice. Results
The biodistribution study indicated that NicNp accumulated in high concentrations in the pancreatic tumors of the mice with Cmax of 138 ± 74.1 µg Nic/g tissue. NicNp treatment, in combination with Gem, worked synergistically to reduce the dose of gemcitabine required to kill pancreatic cancer cells in vitro, two-fold. Additionally, the pancreatic tumor burden in the mouse models was significantly reduced, while survival was significantly increased when mice bearing pancreatic tumors were treated with the combination of NicNp and Gem. Conclusions
This study demonstrates the potential for effective repurposing Nic via nanoformulations in combination with Gem to improve PC treatment efficacy. Lay summary
Pancreatic cancer (PC) ranks among the most lethal types of cancer, with largely ineffective current treatments and toxic side effects in patients. Niclosamide is an FDA-approved anti-parasitic drug with minimal side effects, that has shown some anti-cancer properties. However, it is not effectively absorbed in the body. We produced polymer nanoparticles to deliver niclosamide effectively to treat pancreatic tumors in mice in combination with the chemotherapeutic gemcitabine. This combination treatment led to PC tumor reduction and increased the survival, demonstrating that niclosamide encapsulated in nanoparticles in combination with gemcitabine has the potential to be a more effective treatment for PC
Validating the Ability of IAG933 to Block the Interaction of YAP1 and TEAD in Ovarian Cancer Cells
No full textOvarian cancer is the most common and deadliest gynecologic malignancy. Approximately 40% of ovarian cancer patients exhibit chemoresistance after receiving initial treatment in the form of neoadjuvant chemotherapy or interval debulking surgery, of which YAP1 (Yes-associated protein 1) has been implicated in enhancing the resistance of ovarian cancer to Cisplatin and Taxol.1,2. This highlights the need to develop new therapeutic strategies that target the Hippo pathway to overcome resistance to traditional therapies.
YAP1 is a protein that acts as a transcription coregulator, promoting the transcription of genes involved in cellular proliferation and suppressing apoptotic genes. It is a critical effector of the Hippo signaling pathway, and its activity is driven by its association with the transcriptional enhancer-associated domain (TEAD) family of transcription factors. A novel strategy is to specifically inhibit or block the interaction between YAP1 and TEAD through small molecules, thereby significantly reducing the proliferative capacity and potentially inducing cell death in cancer cells.
This thesis characterized the newly developed IAG933 drug in ovarian cancer cells. Examination includes the confirmation of the blocking of interaction between YAP1 and TEAD protein family members through western blot, cell viability, and the exploration of the possible impacts this blockage has on resistance to therapy and downstream effects concerning processes within the cell
Barriers to Medication-Assisted Treatment for Opioid Use Disorder in Prisons and Jails in the United States: A Comprehensive Literature Review
Full text linkBackground: The American Society for Addiction Medicine guidelines state that all FDA-approved medication for opioid use disorder should be available for all patients (CDC, 2024). Medication-assisted treatments for opioid use disorders, also known as medication for opioid use disorder (MOUD), are treatments that help diminish the physical symptoms of addiction to opioids. Currently, there are three FDA-approved medications to treat opioid use disorder: buprenorphine, methadone, and naltrexone (FDA, 2024). Despite being at an increased risk for opioid misuse and overdose, incarcerated individuals in the U.S. often do not have access to MOUD. This comprehensive literature review aimed to determine the prevailing barriers to MOUD programs in carceral facilities.
Methods: A comprehensive literature search approach was conducted across five databases and scholarly search tools, resulting in 41,395 records from the initial search. The review followed systematic review principles and adhered to a modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A thematic review process using Zotero reference manager and modified MAPiT strategy provided additional analysis and insights, resulting in ten final studies to analyze.
Results: Applying search refinement criteria of the research resulted in (n = 8) qualitative studies that gathered data through interviews, focus groups, surveys, or a combination of these methods—all included studies that identified at least two types of MOUDs. Half of the study settings included only jails (n = 5), less than half (n = 4) included unified jails and prisons, and only one study was limited to just a prison. Study participants in eight of the studies were representatives of the carceral settings, such as administrators, clinicians, or staff—two studies utilized incarcerated individuals as study participants. The identified barriers were categorized into four thematic groups: program, stigma, regulatory, and community barriers.
Conclusion: Despite societal evidence supporting MOUD, many compounding and interdependent barriers such as policy, geography, staffing issues, and resources prevent carceral institutions from adopting best practices for opioid use treatment. Reducing these barriers to MOUD for incarcerated individuals would save thousands of lives every year from overdose
The Impact of Teaching Multiple Responses on Resurgence of Target Behavior and Persistence of Alternative Responding
No full textThis study evaluated the effects of teaching multiple alternative responses on the resurgence of a target response and the persistence of an alternative response in an applied setting. Using a between-participants group design, we examined how teaching multiple alternative responses impacted resurgence and persistence upon exposure to extinction. Additionally, we investigated the role of preference in response allocation and shifts in preference following extinction. Results indicated resurgence across both conditions, with no consistent difference in severity between single and multiple alternative responses. However, within session analysis revealed greater persistence of the alternative response for participants taught multiple responses, suggesting potential benefits for sustained engagement. Preference for alternative responses was influenced by teaching order and reinforcement history, with shifts in preference following extinction. Notably, caregiver predictions of child preference did not align with assessment outcomes, highlighting the need for individualized evaluation. Despite mixed findings, this study proves valuable insights into clinical strategies for promoting alternative responding
Revenue Cycle Management: Audit of a Primary Care Clinic, Strategy, & Future Improvements
Full text linkHealthcare practices that offer primary care, an essential service, are dependent upon financial liquidity for survival. This project evaluated the financial wellbeing of a local primary care clinic through the process of revenue cycle evaluation. The clinic has transitioned from the startup phase into a period of growth and as the clinic scales up, it faces new challenges related to revenue cycle management (RCM) and overall operational efficiency.
For any practice, the process of evaluating the revenue cycle, formally known as Revenue Cycle Management (RCM), is critical to help ensure financial stability. Central to managing the revenue cycle is the process of systemization, by which a practice can begin to standardize the operational the revenue cycle functions for continual improvement. One formal way of conducting an evaluation is by using an RCM audit, where a systematic approach is used to evaluate current revenue cycle processes and functions
Assessing the Impact of Atrazine and Paraquat on Parkinson’s Disease Prevalence in Rural Nebraska Counties
Full text linkThis study examines the association between exposure to the herbicides atrazine and paraquat and the prevalence of Parkinson’s Disease (PD) in various counties of Nebraska. PD is a neurodegenerative disorder that impacts rural agricultural regions in Nebraska, where pesticide application is prevalent. Through a thorough analysis of data sourced from the Nebraska PD Registry, environmental monitoring databases, and pesticide usage, this research aims to establish a correlation between the concentrations of atrazine and paraquat in both groundwater and surface water and the incidence of PD within this region. The study will employ statistical techniques to evaluate this association while accounting for demographic variables, including generalized linear models. Preliminary findings reveal that counties with elevated levels of these pesticides report higher rates of PD. This research addresses a significant gap in the existing literature concerning the specific effects of atrazine and paraquat on risk for PD in Nebraska. The insights derived from this study could inform public health policy and strategies for mitigation. Ultimately, the results may guide the establishment of safer pesticide use guidelines and reinforce protective measures for vulnerable populations, thus contributing to a more comprehensive understanding of the environmental factors that impact neurological health
Evaluating the Therapeutic Potential of Geranylgeranyl Diphosphate Synthase Inhibitor, RAM2061, in Myeloma Bone Disease
No full textMultiple myeloma (MM) is a hematological malignancy of the plasma cells which often results in lytic bone disease. Myeloma bone disease (MBD), characterized by diffuse osteopenia, bone lesions, or pathological fracture, results from MM mediated promotion of osteoclast resorption and dual inhibition of bone formation, drastically reducing bone strength and integrity. Development of MBD is known to significantly impact patient quality of life and increase risk of mortality. Considering that up to 80-95% of MM patients are expected to develop bone disease post-initial MM diagnosis, there is a significant need within this population for therapeutics which address both MM disease and bone health.
The geranylgeranyl diphosphate synthase (GGDPS) inhibitor, RAM2061, exhibits anti-tumor activity in MM cells through depletion of the metabolite, geranylgeranyl diphosphate (GGPP), and disruption of protein prenylation. RAM2061 possesses a unique bisphosphonate moiety indicating potential affinity for bone and furthermore, has a similar mechanism of action (MOA) to clinically used anti-resorptive agents, nitrogen bisphosphonates (NBP). NBP MOA is attributed to depletion of GGPP albeit through inhibition of the enzyme farnesyl diphosphate synthase (FDPS), upstream of GGDPS. Therefore, understanding RAM2061 to deplete intracellular GGPP and exhibit potential bone affinity, suggests anti-resorptive potential. The aims of this work were focused on interrogating the bone-specific affinity of RAM2061 and to characterize the molecular effects of treatment on osteoclast and osteoblast function.
Studies presented throughout this dissertation confirm RAM2061 bone affinity and disruption of osteoclast differentiation/resorption through inhibition of Rho GTPase geranylgeranylation. Anti-resorptive effects in vivo were less pronounced but validated by reduced osteoclast number in RAM2061 treated mice. RAM2061-treated osteoblast precursors displayed reduced differentiation activity and overall function. Finally, studies were pursued in which RAM2061 was combined with proteasome inhibitor bortezomib, as this commonly used anti-MM agent has been reported to have bone-protective effects. Preliminary studies presented here suggest no appreciable changes in RAM2061 effects on bone cells when used in combination with bortezomib, however studies under MBD-like conditions revealed the importance of evaluating drug efficacy in consideration of MM microenvironmental effects. Future studies aim to interrogate the in vivo application of RAM2061 in reducing both MM and bone disease morbidity and further elucidating translational effects underlying MOAs on overall quality of life and survival
Intrinsic and Extrinsic Drivers of Bioaerosol Decay: Investigating Pathogen Stability of Bacteriophage MS2, Sin Nombre Virus, and SARS-COV-2 in Simulated Environments
No full textThe threat posed by a virus as a bioaerosol depends largely on its stability under various environmental conditions (relative humidity (RH), sunlight, ozone, etc.). This stability is typically studied through aerosol decay—how the virus\u27 viability changes over time when exposed environmental conditions. The Goldberg rotating drum, a widely used tool for studying bioaerosols, has been the basis of such research (Goldberg et al., 1958). However, it has significant limitations, including an inability to measure initial pathogen infectivity loss and the use of small sample volumes. Additionally, it does not answer the question of what intrinsic factors (lipids, proteins, nucleic acids) cause a virus to become inactivated after exposure.
To address these challenges, we designed the Biological Aerosol Reaction Chamber (Bio-ARC), a novel flow-through system designed to expose large quantities of bioaerosols to controlled environmental conditions. This innovative approach allows for a more in-depth analysis of aerosol decay mechanisms. This was confirmed with the use of Bacteriophage MS2 (Chapter 2), which also found that the Bio-ARC witnesses the dynamic decay profile.
Following BSL-2 work, we moved the Bio-ARC into the BSL-3. There we investigated the aerostability of two viruses with distinct transmission pathways: Sin Nombre Virus (SNV), which spreads via inhalation of contaminated rodent excreta (Chapter 3), and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which transmits through respiratory fluids (Chapter 4). Despite similarities as enveloped viruses with comparable protein structures, these pathogens differ significantly in their transmission routes. For the first time, we report aerostability data for SNV, alongside findings on the sensitivity of SARS-CoV-2 to ozone, simulated sunlight, and relative humidity. Additionally, we have begun to answer which intrinsic factors are responsible for virus inactivation when exposed to environmental conditions. These insights not only deepen our understanding of aerosolized virus behavior but also pave the way for more effective public health interventions for SNV and SARS-CoV-2