The Overlap of Interstitial Cystitis/Painful Bladder Syndrome and Overactive Bladder

Results of this study suggest that patients who have failed therapies for overactive bladder might be more effectively treated using therapies directed towards uroepithelial dysfunction and neural upregulation associated with interstitial cystitis

Methylation of HOXA9 and ISL1 predicts patient outcome in high-grade non-invasive bladder cancer

Introduction Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Methods Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases. Results The ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM). Conclusions In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC

Cost-effectiveness of external cephalic version for term breech presentation

<p>Abstract</p> <p>Background</p> <p>External cephalic version (ECV) is recommended by the American College of Obstetricians and Gynecologists to convert a breech fetus to vertex position and reduce the need for cesarean delivery. The goal of this study was to determine the incremental cost-effectiveness ratio, from society's perspective, of ECV compared to scheduled cesarean for term breech presentation.</p> <p>Methods</p> <p>A computer-based decision model (TreeAge Pro 2008, Tree Age Software, Inc.) was developed for a hypothetical base case parturient presenting with a term singleton breech fetus with no contraindications for vaginal delivery. The model incorporated actual hospital costs (e.g., $8,023 for cesarean and$5,581 for vaginal delivery), utilities to quantify health-related quality of life, and probabilities based on analysis of published literature of successful ECV trial, spontaneous reversion, mode of delivery, and need for unanticipated emergency cesarean delivery. The primary endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted year of life gained. A threshold of $50,000 per quality-adjusted life-years (QALY) was used to determine cost-effectiveness.</p> <p>Results</p> <p>The incremental cost-effectiveness of ECV, assuming a baseline 58$7,900/QALY. If the estimated probability of successful ECV is less than 32%, then ECV costs more to society and has poorer QALYs for the patient. However, as the probability of successful ECV was between 32% and 63%, ECV cost more than cesarean delivery but with greater associated QALY such that the cost-effectiveness ratio was less than $50,000/QALY. If the probability of successful ECV was greater than 63%, the computer modeling indicated that a trial of ECV is less costly and with better QALYs than a scheduled cesarean. The cost-effectiveness of a trial of ECV is most sensitive to its probability of success, and not to the probabilities of a cesarean after ECV, spontaneous reversion to breech, successful second ECV trial, or adverse outcome from emergency cesarean.</p> <p>Conclusions</p> <p>From society's perspective, ECV trial is cost-effective when compared to a scheduled cesarean for breech presentation provided the probability of successful ECV is > 32%. Improved algorithms are needed to more precisely estimate the likelihood that a patient will have a successful ECV.</p

Department of Animal Sciences research and reviews: beef and sheep

Relationship of a PCR-SSCP at the Bovine calpastatin locus with calpastatin activity and meat tenderness / H. Y. Chung, M. E. Davis, H. C. Hines, and D. M. Wulf -- Effects of calpain proteolysis and calpain genotypes on meat tenderness of angus bulls / H. Y. Chung, M. E. Davis, H. C. Hines, and D. M. Wulf -- Identification of genetic markers for growth and carcass traits in beef cattle / W. Ge, M. E. Davis, H. C. Hines, and K. M. Irvin -- Relationships of polymorphisms in the bovine leptin gene with differences in beef carcass traits / K. Tessanne, H. C. Hines, and M. E. Davis -- Effects of rate of gain during periods of restricted intake on performance and carcass characteristics in steers fed to achieve step-wise increases in rate of gain / J. E. Rossi and S. C. Loerch -- Effects of feeding regimen and days fed on performance and carcass characteristics of feedlot steers / J. E. Rossi, S. C. Loerch, S. J. Moeller, and J. P. Schoonmaker -- Effect of an accelerated finishing program on performance and carcass characteristics of early weaned bulls and steers / J. P. Schoonmaker, S. C. Loerch, F. L. Fluharty, T. B. Turner, S. J. Moeller and J. E. Rossi -- Yeast-mineral mixes and beef-cattle performance in fescue-based grazing systems: preliminary report / S. Boyles, W. Shriver, and D. Kobs -- Forage and animal evaluation of heifers at Indian Lake Hydrologic Unit CRP stocker grazing demonstration / S. L. Boyles, B. W. Stoll, and T. L. Dobbels -- Beef quality is every cattleman's business: education program / J. Yates and S. Boyles -- Effects of pelleted alfalfa and whole-shelled corn combinations on lamb growth and carcass characteristics / F. L. Fluharty -- Effects of feeding pelleted, ensiled, or a combination of pelleted and ensiled alfalfa on lamb growth and carcass characteristics / F. L. Fluharty, G. D. Lowe, and D. D. Clevenger -- Effects of corn silage vs. alfalfa haylage on lamb growth and carcass characteristics in forage-based finishing systems / F. L. Fluharty, G. D. Lowe, and D. D. Clevenger -- Effects of feed-delivery system and corn processing on lamb growth and carcass characteristics / F. L. Fluharty, G. D. Lowe, and D. D. Clevenger -- Effects of pen floor type and bedding on lamb growth and carcass characteristics / F. L. Fluharty, G. D. Lowe, and D. D. Clevenger -- A PCR-SSCP polymorphism detected in the 5' flanking region of the ovine IGF-I gene / A. Yilmaz, M. E. Davis, and H. C. Hine

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807