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Renal lithiasis is known for its high incidence and prevalence, but mainly for its morbidity and recurrence. Despite a good indication and appropriate surgical treatment, the essential problem, the origin of the formation of the stones, generally persists and it is not uncommon that patients suffer multiple treatments and discomfort secondary to ancillary measures normally used to prevent complications. It is widely known, for consistency, that a prophylactic treatment with general or, in a smaller group of patients, specific measures are appropriate to diminish recurrences. Nevertheless, prophylaxis is not usually used by many urologists and, on top of that, in the majority of those cases when it is taken into consideration, it is the patient who fails for inadequate treatment compliance. It is very important, in any of our conversations with the urinary lithiasis' patient in relation with the disease, that the urologist provides a proper and detailed information about all its features, from diagnosis to active treatment and possible complications and, of course in those cases where prophylaxis is going to be essential to avoid new unpleasant episodes of pain and associated surgical interventions, emphasizing that improving his/her quality of life depends, to a great extent, on the patient himself. In this article, considering the existing evidence and personal experience, we intend to detail those behaviors we should take into consideration to facilitate the patient both therapeutic decisions and a positive attitude towards his/her disease, with the aim to control it in the best possible way.

Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles. We report that RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein. We demonstrate the differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography, and describe the structural differences driving the BD2 selective binding of RVX-297. The isothermal titration calorimetry (ITC) data illustrate the related differential thermodynamics of binding of RVX-297 to single as well as dual BET bromodomains., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Tumor characteristics affect surgical complexity and outcomes of partial nephrectomy (PN)., Objective: To develop an Arterial Based Complexity (ABC) scoring system to predict morbidity of PN., Design, Setting, and Participants: Four readers independently scored contrast-enhanced computed tomography images of 179 patients who underwent PN., Intervention: Renal cortical masses were categorized by the order of vessels needed to be transected/dissected during PN. Scores of 1, 2, 3S, or 3H were assigned to tumors requiring transection of interlobular and arcuate arteries, interlobar arteries, segmental arteries, or in close proximity of the renal hilum, respectively during PN., Outcome Measurements and Statistical Analysis: Interobserver variability was assessed with kappa values and percentage of exact matches between each pairwise combination of readers. Linear regression was used to evaluate the association between reference scores and ischemia time, estimated blood loss, and estimated glomerular filtration rates at 6 wk and 6 mo after surgery adjusted for baseline estimated glomerular filtration rate. Fisher's exact test was used to test for differences in risk of urinary fistula formation by reference category assignment., Results and Limitations: Pairwise comparisons of readers' score assignments were significantly correlated (all p<0.0001); average kappa = 0.545 across all reader pairs. The average proportion of exact matches was 69%. Linear regression between the complexity score system and surgical outcomes showed significant associations between reference category assignments and ischemia time (p<0.0001) and estimated blood loss (p=0.049). Fisher's exact test showed a significant difference in risk of urinary fistula formation with higher reference category assignments (p=0.028). Limitations include use of a single institutional cohort to evaluate our system., Conclusions: The ABC scoring system for PN is intuitive, easy to use, and demonstrated good correlation with perioperative morbidity., Patient Summary: The ABC scoring system is a novel anatomy-reproducible tool developed to help patients and doctors understand the complexity of renal masses and predict the outcomes of kidney surgery., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze if there is a learning curve to get to perform high quality ultrasound guided prostate biopsies that enable to effectively perform the diagnosis of prostate cancer, taking the pathological result of the samples into consideration., Methods: We retrospectively reviewed data from 790 ultrasound-guided biopsies performed consecutively in our center between May 2009 and December 2012 by four surgeons. We reviewed the following data: Surgeon, date of intervention, patient age, PSA, rectal digital examination (DRE), ultrasound, prostate volume, number of cores obtained, pathology result of the biopsy. The surgeons were residents in Urology in their first year in the department. For statistical analysis the biopsies were grouped in blocks of 25 and 75 cases performed by a surgeon, in a chronological order. To evaluate the influence of the learning curve on diagnosis we performed univariate and multivariate analysis between the different variables and pathological report., Results: Median age was 67 years (42-90). 300 biopsies (38%) were positive for prostate cancer. On univariate analysis, regarding cancer detection rate, the variables surgeon, PSA, DRE, ultrasound result, prostate volume, number of cores and groups of 75 showed statistically significant differences, this latter showing 32% in the first 75 biopsies and 43.2% in the last group. The variables age (p=0.11) and groups of 25 patients (p=0.07) did not show differences. Nevertheless, on multivariate analysis only PSA, DRE, prostate volume and groups of 75 patients were statistically significant, this latter with an OR of 1.35 (95%CI 1.09-1.66)., Conclusions: The results obtained in our study show that the number of procedures performed, namely surgeon experience, does have an influence to achieve an optimal diagnostic yield in ultrasound guided prostatic biopsies.

Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.

Background: The present study was aimed at determining the prophylactic efficacy of American cranberry (AC) extract (Cysticlean®) in women with recurrent symptomatic postcoital urinary tract infections (PCUTI), non-consumer of AC extract in the past 3 months before inclusion, and to determine changes in their quality of life (QoL)., Methods: This was a single center, observational, prospective study in a total of 20 women (mean age 35.2 years; 50.0% were married). Patients were followed up for 3 and 6 months during treatment., Results: The number of PCUTIs in the previous 3 months prior to start the treatment with Cysticlean® was 2.8±1.3 and it was reduced to 0.2±0.5 at Month 6 (P<0.0001), which represent a 93% improvement. At baseline, the mean score on the VAS scale (range from 0 to 100) for assessing the QoL was 62.4±19.1, increasing to 78.2±12.4 at Month 6 (P=0.0002), which represents a 20% improvement. All patients had an infection with positive urine culture at baseline, after 6 months there were only 3 symptomatic infections (P<0.001). The most common bacterium was Escherichia coli., Conclusions: Prophylaxis with American cranberry extract (Cysticlean®) could be an alternative to classical therapies with antibiotics. Further studies are needed to confirm results obtained in this pilot study.

The seven-residue peptide GNNQQNY from the N-terminal region of the yeast prion protein Sup35, which forms amyloid fibers, colloidal aggregates and highly ordered nanocrystals, provides a model system for characterizing the elusively protean cross-beta conformation. Depending on preparative conditions, orthorhombic and monoclinic crystals with similar lath-shaped morphology have been obtained. Ultra high-resolution (<0.5A spacing) electron diffraction patterns from single nanocrystals show that the peptide chains pack in parallel cross-beta columns with approximately 4.86A axial spacing. Mosaic striations 20-50 nm wide observed by electron microscopy indicate lateral size-limiting crystal growth related to amyloid fiber formation. Frequently obtained orthorhombic forms, with apparent space group symmetry P2(1)2(1)2(1), have cell dimensions ranging from /a/=22.7-21.2A, /b/=39.9-39.3A, /c/=4.89-4.86A for wet to dried states. Electron diffraction data from single nanocrystals, recorded in tilt series of still frames, have been mapped in reciprocal space. However, reliable integrated intensities cannot be obtained from these series, and dynamical electron diffraction effects present problems in data analysis. The diversity of ordered structures formed under similar conditions has made it difficult to obtain reproducible X-ray diffraction data from powder specimens; and overlapping Bragg reflections in the powder patterns preclude separated structure factor measurements for these data. Model protofilaments, consisting of tightly paired, half-staggered beta strands related by a screw axis, can be fit in the crystal lattices, but model refinement will require accurate structure factor measurements. Nearly anhydrous packing of this hydrophilic peptide can account for the insolubility of the crystals, since the activation energy for rehydration may be extremely high. Water-excluding packing of paired cross-beta peptide segments in thin protofilaments may be characteristic of the wide variety of anomalously stable amyloid aggregates.

To demonstrate that crystallographic methods can be applied to index and interpret diffraction patterns from well-ordered quasicrystals that display non-crystallographic 5-fold symmetry, we have characterized the properties of a series of periodic two-dimensional lattices built from pentagons, called Fibonacci pentilings, which resemble aperiodic Penrose tilings. The computed diffraction patterns from periodic pentilings with moderate size unit cells show decagonal symmetry and are virtually indistinguishable from that of the infinite aperiodic pentiling. We identify the vertices and centers of the pentagons forming the pentiling with the positions of transition metal atoms projected on the plane perpendicular to the decagonal axis of quasicrystals whose structure is related to crystalline eta phase alloys. The characteristic length scale of the pentiling lattices, evident from the Patterson (autocorrelation) function, is approximately tau 2 times the pentagon edge length, where tau is the golden ratio. Within this distance there are a finite number of local atomic motifs whose structure can be crystallographically refined against the experimentally measured diffraction data.