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Item DEFA1A3 DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection(Cold Spring Harbor Laboratory, 2024-04-05) Canas, Jorge J.; Arregui, Samuel W.; Zhang, Shaobo; Knox, Taylor; Calvert, Christi; Saxena, Vijay; Schwaderer, Andrew L.; Hains, David S.; Pediatrics, School of MedicineAntimicrobial peptides (AMPs) are host defense effectors with potent neutralizing and immunomodulatory functions against invasive pathogens. The AMPs α-Defensin 1-3/DEFA1A3 participate in innate immune responses and influence patient outcomes in various diseases. DNA copy-number variations in DEFA1A3 have been associated with severity and outcomes in infectious diseases including urinary tract infections (UTIs). Specifically, children with lower DNA copy numbers were more susceptible to UTIs. The mechanism of action by which α-Defensin 1-3/DEFA1A3 copy-number variations lead to UTI susceptibility remains to be explored. In this study, we use a previously characterized transgenic knock-in of the human DEFA1A3 gene mouse to dissect α-Defensin 1-3 gene dose-dependent antimicrobial and immunomodulatory roles during uropathogenic Escherichia coli (UPEC) UTI. We elucidate the relationship between kidney neutrophil- and collecting duct intercalated cell-derived α-Defensin 1-3/DEFA1A3 expression and UTI. We further describe cooperative effects between α-Defensin 1-3 and other AMPs that potentiate the neutralizing activity against UPEC. Cumulatively, we demonstrate that DEFA1A3 directly protects against UPEC meanwhile impacting pro-inflammatory innate immune responses in a gene dosage-dependent manner.Item Deleted in malignant brain tumor 1 genetic variation confers urinary tract infection risk in children and mice(Wiley, 2021-07) Hains, David S.; Polley, Shamik; Liang, Dong; Saxena, Vijay; Arregui, Samuel; Ketz, John; Barr-Beare, Evan; Rawson, Ashley; Spencer, John D.; Cohen, Ariel; Hansen, Pernille L.; Tuttolomondo, Martina; Casella, Cinzia; Ditzel, Henrik J.; Cohen, Daniel; Hollox, Edward J.; Schwaderer, Andrew L.; Pediatrics, School of MedicineItem Urinary Tract Infections: Pediatric Primary Care Curriculum Podcast(Association of American Medical Colleges, 2016-08-05) Reid Burks, Allison; Nicklas, Daniel; Owens, Jason; Lockspeiser, Tai Mara; Soranno, Danielle E.; Pediatrics, School of MedicineIntroduction: Demands on residents' time during training make it difficult for them to engage consistently with a primary care curriculum. In response to this, the emergency medicine and critical care fields have successfully utilized podcasting to the point where a recent study showed US emergency medicine residents ranked podcasts as the best use of their time for extracurricular education. Methods: We produced a 30-minute podcast on urinary tract infections from a primary care perspective, based on descriptors from Entrustable Professional Activity 4, "Manage acute common illnesses in the ambulatory setting." A moderator, a primary care pediatrician, and a pediatric nephrologist used a loose script of salient points, allowing for a natural evolution of the dialogue. The podcast was distributed to residents via email, along with a 7-question survey. Results: The survey was completed by 50 out of 84 residents. Ninety-two percent listened to all or part of the podcast, 98% found it educational, 93% enjoyed listening, and 74% felt more confident identifying and managing patients with possible urinary tract infections after listening. Ninety-six percent felt podcasts were a good alternative method for delivering this curriculum. One comment read, "This was great! It makes the information more accessible so that I can listen while working out or driving or just laying on the couch." Discussion: Based on this success, we are producing additional podcasts and will strive to keep them under 20 minutes, provide key summary points at the end, and improve ease of access by utilizing an RSS (rich site summary) feed.