Browsing by Subject "Cystic Fibrosis"
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Item Interprofessional Accredited Continuing Education for the Healthcare Team: A Review of 7 Cystic Fibrosis Courses(2023-04-28) Denny, Kim M.; Patel, Rima; Howenstine, Michelle S.INTRODUCTION: For accredited continuing education to be categorized as interprofessional, each activity must meet certain criteria as defined by the Joint Accreditation for Interprofessional Continuing Education (JA) including an integrated planning process that includes health care professionals from 2 or more professions who are reflective of the target audience members the activity is designed to address, an instructional design intent to achieve outcome(s) that reflect a change in skills, strategy, or performance of the health care team and/or patient outcomes; reflection of 1 or more of the interprofessional competencies; opportunities for learners to learn with, from, and about each other; and evaluation that seeks to determine changes in skills, strategy, performance of one's role or contribution as a member of the healthcare team; and/or impact on the healthcare team; and/or impact on patient outcomes. METHODS: Analysis of instructional design factors and learner data from 7 Courses (7 Enduring Activities each with 4-6 Modules); use data about what was accomplished to analyze the degree to which we met our goals of developing interprofessional accredited CE Courses. Data points to include: Diversity of Planning team members (healthcare professionals from 2 or more professions); An intent to achieve outcome(s) that reflect a change in skills, strategy, or performance of the health care team and/or patient outcomes; Addressing interprofessional competencies (to include): values/ ethics, roles/ responsibilities, interprofessional communication, and teams/teamwork; An opportunity for learners to learn with, from, and about each other (active learning); Post-activity evaluations that seek to determine: Changes in skills, strategy, performance of one's role or contribution as a member of the healthcare team; and/or Impact on the healthcare team; and/or Impact on patient outcomes. CONCLUSION: These Cystic Fibrosis 7 Courses are strong examples of Interprofessional accredited continuing education for the healthcare team. This model of CE Courses to address clinical practice gaps is a blueprint that can be utilized for other IU schools and departments.Item Molecular mechanisms of cytotoxicity regulation in pseudomonas aeruginosa by the magnedium transporter MGTE(2017-07) Chakravarty, Shubham; Anderson, Gregory G.The Gram-negative bacterium Pseudomonas aeruginosa causes numerous acute and chronic opportunistic infections in humans. One of its most formidable weapons is a type III secretion system (T3SS), a multi-protein molecular syringe that injects powerful toxins directly into host cells. The toxins lead to cell dysfunction and, ultimately, cell death. Identification of regulatory pathways that control T3SS gene expression may lead to the discovery of novel therapeutics to treat P. aeruginosa infections. In a previous study, it was found that expression of the magnesium transporter gene mgtE inhibits T3SS gene transcription. MgtE-dependent inhibition appeared to interfere with the synthesis or function of the master T3SS transcriptional activator ExsA, although the exact mechanism was unclear. In this work, we demonstrate that mgtE expression acts through the GacAS two-component system to activate transcription of the small regulatory RNAs RsmY and RsmZ. This event ultimately leads to inhibition of exsA translation. Moreover, our data reveal that MgtE acts solely through this pathway to regulate T3SS gene transcription. Our study reveals an important mechanism that may allow P. aeruginosa to fine-tune T3SS activity in response to certain environmental stimuli. In addition, a previous study has shown that the P. aeruginosa gene algR abrogates mgtE mediated regulation of cytotoxicity. AlgR has pleiotropic effects in P. aeruginosa, including regulation of synthesis of the exopolysaccharide alginate. In the second part of my thesis, I show that algR and mgtE genetically crosstalk to inhibit ExsA driven T3SS gene transcription. This genetic interaction between algR and mgtE seems to be specifically directed towards regulation of T3SS gene expression rather than having an indiscriminate effect on multiple virulence attributes in P. aeruginosa. Additionally, we have further demonstrated that AlgR inhibits mgtE transcription. These studies suggest the presence of a T3SS inhibitor that is inhibited by both AlgR and MgtE. Future work will involve transcriptomic and proteomic analysis to identify such an inhibitor. Taken together, this study provides important insight into the molecular mechanisms of mgtE expression and function in P. aeruginosa. We have established that mgtE has pleiotropic effects on cytotoxicity in P. aeruginosa. Thus, given the role that cytotoxicity regulation plays in shaping P. aeruginosa pathogenesis and associated clinical outcomes, mgtE might be an interesting drug target, though extensive future studies are required to validate this proposition. Nevertheless, this research, provides clues for identification of novel therapeutic targets in P. aeruginosa. Hence this work, in the long run, serve to ameliorate the morbidity and mortality in patients infected with P. aeruginosa.Item Pancreas transplantation for Cystic Fibrosis: A Frequently Missed Opportunity(Wiley, 2021-09) Fridell, Jonathan A.; Bozic, Molly A.; Ulrich, Benjamin J.; Lutz, Andrew J.; Powelson, John A.; Surgery, School of MedicineCystic fibrosis (CF) is an inherited autosomal recessive disorder. Despite optimized therapy, the majority of affected individuals ultimately die of respiratory failure. As patients with CF are living longer, extra-pulmonary manifestations may develop including pancreatic failure, which manifests as exocrine insufficiency, and CF related diabetes (CFRD). Both of these can be managed through pancreas transplantation. Pancreas transplantation is usually performed in combination with another organ, most often with a kidney transplant for end-stage diabetic nephropathy. In the CF patient population, the two settings where inclusion of a pancreas transplant should be considered would be in combination with a lung transplant for CF pulmonary disease, or in combination with a liver for CF related liver disease with cirrhosis. This report will discuss this topic in detail, including a review of the literature regarding combinations of lung/pancreas and liver/pancreas transplant.Item Using Amino Acid Derivatives to Inhibit Pseudomonas aeruginosa Biofilm Formation on Cystic Fibrosis Bronchial Epithelia Cells(Office of the Vice Chancellor for Research, 2014-04-11) LaCombe, Jonathan M.; Anderson, Gregory G.; Marrs, Kathleen A.Cystic Fibrosis is a genetic disease caused by a mutation which inhibits the proper transport of sodium and chloride ions across epithelium. Improper ion transport results in the accumulation of thick mucus in critical organs such as the lungs, pancreas, liver, and intestines. The genetic mutation is incurable, but treating the symptoms can vastly increase life expectancy. CF patients are often afflicted with bacterial infections which colonize the excess mucus within the lungs. The most prevalent pathogen associated with CF lung infection is Pseudomonas aeruginosa, a Gram-negative bacterium found in soil and water. Pseudomonas aeruginosa exists in two forms: planktonic (free-swimming) and sessile (immobile within a biofilm community). The planktonic form is about 1,000x more susceptible to antibiotics and immune cells than the sessile form. Biofilm communities of sessile bacteria are protected by an exopolysaccharide layer outside of the cell wall. Small molecules which inhibit biofilm formation or initiate biofilm disassembly can dramatically increase the effectiveness of drugs and the immune system. In order to identify novel biofilm-inhibitory molecules, we assessed the activity of a library of small molecules in biofilm assays. Active compounds were then screened for activity on living Cystic Fibrosis bronchial epithelial cells infected with Pseudomonas aeruginosa. Compounds which successfully inhibit biofilm formation without affecting the Cystic Fibrosis bronchial epithelium cells can potentially be a new drug for treating Cystic Fibrosis infections.