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Item DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk(Sage, 2020-08) Qureshi, Aslam H.; Liang, Dong; Canas, Jorge; Hooks, Jenaya; Arrregui, Samuel W.; Saxena, Vijay; Rooney, Robert; Nolan, Vikki; Schwaderer, Andrew L.; Hains, David S.; Pediatrics, School of MedicineUrinary tract infections (UTI), associated with vesicoureteral reflux (VUR), can lead to chronic kidney disease. Genetic alterations in the innate immune defenses contribute to UTI risk. We investigated a novel gene, Dachsous Cadherin-Related 1 ( DCHS1), in children with UTI. We determined absolute DNA copy number (CN) of DCHS1 in children with UTI. In this case-control study, we utilized multiple complementary methods to determine the genomic CN of DCHS1. Children with ( n = 370) and without ( n = 71) VUR from two well-phenotyped clinical trials of UTI were copy-typed and compared to 491 healthy controls with no known history of VUR or UTI. Less than 1% of controls had a single copy of DCHS1, while 31% of children with UTI and no VUR and 7% of children with UTI and VUR had a single copy of the DCHS1 gene. Using immunostaining, we localized expression postnatally to the bladder and renal epithelia. Mice were also challenged with two uropathogenic Escherichia coli strains, and Dchs1 mRNA was quantified. This study represents the first report of DCHS1 in association with pediatric UTI. We hypothesize that its role in innate immunity is critical to lower urinary tract defense. Further investigation is required to determine the role of DCHS1 in innate immunity.Item DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk(SAGE, 2020-04-15) Qureshi, Aslam H.; Liang, Dong; Canas, Jorge; Hooks, Jenaya; Arrregui, Samuel W.; Saxena, Vijay; Rooney, Robert; Nolan, Vikki; Schwaderer, Andrew L.; Hains, David S.; Pediatrics, School of MedicineUrinary tract infections (UTI), associated with vesicoureteral reflux (VUR), can lead to chronic kidney disease. Genetic alterations in the innate immune defenses contribute to UTI risk. We investigated a novel gene, Dachsous Cadherin-Related 1 (DCHS1), in children with UTI. We determined absolute DNA copy number (CN) of DCHS1 in children with UTI. In this case-control study, we utilized multiple complementary methods to determine the genomic CN of DCHS1. Children with (n = 370) and without (n = 71) VUR from two well-phenotyped clinical trials of UTI were copy-typed and compared to 491 healthy controls with no known history of VUR or UTI. Less than 1% of controls had a single copy of DCHS1, while 31% of children with UTI and no VUR and 7% of children with UTI and VUR had a single copy of the DCHS1 gene. Using immunostaining, we localized expression postnatally to the bladder and renal epithelia. Mice were also challenged with two uropathogenic Escherichia coli strains, and Dchs1 mRNA was quantified. This study represents the first report of DCHS1 in association with pediatric UTI. We hypothesize that its role in innate immunity is critical to lower urinary tract defense. Further investigation is required to determine the role of DCHS1 in innate immunity.Item Preoperative Bladder Urine Culture as a Predictor of Intraoperative Stone Culture Results: Clinical Implications and Relationship to Stone Composition(Elsevier, 2016-09) Paonessa, Jessica E.; Gnessin, Ehud; Bhojani, Bhojani; Williams, James C.; Lingeman, James E.; Anatomy and Cell Biology, School of MedicinePurpose We examine the relationship between urine and stone cultures in a large cohort of patients undergoing percutaneous stone removal and compare the findings in infectious vs metabolic calculi. Materials and Methods A total of 776 patients treated with percutaneous nephrolithotomy who had preoperative urine cultures and intraoperative stone cultures were included in the study. Statistical analysis used chi-square or logistic fit analysis as appropriate. Results Preoperative urine culture was positive in 352 patients (45.4%) and stone cultures were positive in 300 patients (38.7%). There were 75 patients (9.7%) with negative preoperative cultures who had positive stone cultures, and in patients with both cultures positive the organisms differed in 103 (13.3%). Gram-positive organisms predominated in preoperative urine and stone cultures. Conclusions Preoperative urine cultures in patients undergoing percutaneous nephrolithotomy are unreliable as there is a discordance with intraoperative stone cultures in almost a quarter of cases. There has been a notable shift toward gram-positive organisms in this cohort of patients.Item Preoperative Bladder Urine Culture as a Predictor of Intraoperative Stone Culture Results: Clinical Implications and Relationship to Stone Composition(Elsevier, 2016-09) Paonessa, Jessica E.; Gnessin, Ehud; Bhojani, Naeem; Williams, James C.; Lingeman, James E.; Anatomy and Cell Biology, School of MedicinePurpose We examine the relationship between urine and stone cultures in a large cohort of patients undergoing percutaneous stone removal and compare the findings in infectious vs metabolic calculi. Materials and Methods A total of 776 patients treated with percutaneous nephrolithotomy who had preoperative urine cultures and intraoperative stone cultures were included in the study. Statistical analysis used chi-square or logistic fit analysis as appropriate. Results Preoperative urine culture was positive in 352 patients (45.4%) and stone cultures were positive in 300 patients (38.7%). There were 75 patients (9.7%) with negative preoperative cultures who had positive stone cultures, and in patients with both cultures positive the organisms differed in 103 (13.3%). Gram-positive organisms predominated in preoperative urine and stone cultures. Conclusions Preoperative urine cultures in patients undergoing percutaneous nephrolithotomy are unreliable as there is a discordance with intraoperative stone cultures in almost a quarter of cases. There has been a notable shift toward gram-positive organisms in this cohort of patients.