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ABSTRACT Introduction: The ureteral access sheath (UAS) is a medical device that enables repeated entrance into the ureter and collecting system during retrograde intrarenal surgery (RIRS). Its impact on stone-free rates, ureteral injuries, operative time, and postoperative complications remains controversial. Therefore, we performed a systematic review and meta-analysis comparing RIRS with versus without UAS for urolithiasis management. Purpose: To compare outcomes from retrograde intrarenal surgery (RIRS) for stone extraction with or without ureteral access sheath (UAS); evaluating stone-free rate (SFR), ureteral injuries, operative time, and postoperative complications. Materials and Methods: We systematically searched PubMed, Embase, and Cochrane Library in June 2024 for randomized controlled trials (RCTs) evaluating the efficacy and safety outcomes of UAS use in RIRS for urolithiasis treatment. Articles published between 2014 and 2024 were included. Pooled risk ratios (RRs) and mean differences (MDs) were calculated for binary and continuous outcomes, respectively. Results: Five RCTs comprising 466 procedures were included. Of these, 246 (52.7%) utilized UAS. The follow-up ranged from 1 week to 1 month. UAS reduced the incidence of postoperative fever (RR 0.49; 95% confidence interval [CI] 0.29–0.84; p=0.009), and postoperative infection (RR 0.50; 95% CI 0.30–0.83; p=0.008). There were no significant differences between groups in terms of SFR (RR 1.05; 95% CI 0.99–1.11; p=0.10), ureteral injuries (RR 1.29; 95% CI 0.95–1.75; p=0.11), operative time (MD 3.56 minutes; 95% CI −4.15 to 11.27 minutes; p=0.36), or length of stay (MD 0.32 days; 95% CI −0.42 to 1.07 days; p=0.40). Conclusion: UAS leads to a lower rate of post-operative fever and infection. However, UAS did not significantly reduce or increase the SFR or the rate of ureteral injuries during RIRS for patients with urolithiasis. The use of UAS should be considered to decrease the risk of infectious complications, particularly in those who may be at higher risk for such complications.

ABSTRACT Purpose: to identify risk factors for urinary septic shock in patients who underwent percutaneous nephrolithotomy (PCNL). Materials and Methods: Data from PCNL procedures performed between January 2009 and February 2020 were retrospectively analyzed. The study included all patients over 18 years old with kidney stones larger than 15 mm who underwent PCNL. Patients who underwent mini-PCNL or combined surgeries, such as ureteroscopy or bilateral procedures, were not included in the study. Logistic regression was conducted to determine the risk factors for urinary septic shock within 30 days post-operation in patients who underwent PCNL. Results: Urinary septic shock was observed in 8 out of the 1,424 patients analyzed (0.56%). The presence of comorbidities, evaluated using the Charlson Comorbidity Index (CCI) (OR 1.46 [CI 95% 1.15-1.86], p=0.01), larger stones (41.0 mm [IQR 30.0-47.5 mm] vs. 24.0 mm [IQR 17.0-35.0 mm], OR 1.03 [CI 95% 1.01-1.06], p=0.04), and a positive preoperative urine culture (OR 8.53 [CI 95% 1.71-42.45], p 2, larger stones (≥ 35 mm), and a positive preoperative urine culture were at even higher risk of urinary septic shock (OR 15.40 [CI 95% 1.77-134.21], p=0.01). Conclusion: Patients with larger stones, positive preoperative urine culture, and a higher CCI are at risk for urinary septic shock after PCNL. These findings are of utmost importance for optimizing the perioperative care of these patients to prevent life-threatening complications.

Abstract Association with hypomethylating agents is a promising strategy to improve the efficacy of immune checkpoint inhibitors-based therapy. The NIBIT-M4 was a phase Ib, dose-escalation trial in patients with advanced melanoma of the hypomethylating agent guadecitabine combined with the anti-CTLA-4 antibody ipilimumab that followed a traditional 3 + 3 design (NCT02608437). Patients received guadecitabine 30, 45 or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks starting on week 0 for a total of four cycles, and ipilimumab 3 mg/kg intravenously starting on day 1 of week 1 every 3 weeks for a total of four cycles. Primary outcomes of safety, tolerability, and maximum tolerated dose of treatment were previously reported. Here we report the 5-year clinical outcome for the secondary endpoints of overall survival, progression free survival, and duration of response, and an exploratory integrated multi-omics analysis on pre- and on-treatment tumor biopsies. With a minimum follow-up of 45 months, the 5-year overall survival rate was 28.9% and the median duration of response was 20.6 months. Re-expression of immuno-modulatory endogenous retroviruses and of other repetitive elements, and a mechanistic signature of guadecitabine are associated with response. Integration of a genetic immunoediting index with an adaptive immunity signature stratifies patients/lesions into four distinct subsets and discriminates 5-year overall survival and progression free survival. These results suggest that coupling genetic immunoediting with activation of adaptive immunity is a relevant requisite for achieving long term clinical benefit by epigenetic immunomodulation in advanced melanoma patients.

ABSTRACT Introduction: We aim to publish our innovative modified biplanar 0-90 endoscopic guided puncture technique for percutaneous nephrolithotomy in supine recorded with a GoPro® camera for standardization of the technique. It solves drawbacks of the fluoroscopic technique, i.e., in kidneys with complex anatomy, it may be challenging to distinguish calyces as they are often superposed, and it does not allow for all benefits of a combined endoscopic approach (1, 2). Our technique shortens puncture and fluoroscopic time and is easy to teach and reproduce. Methods: A 77-year-old female patient had previous double J insertion due to an obstructing stone in the right distal ureter. She managed to pass the distal stone but remained with the double J and a 20mm stone (1300HU) in the right renal pelvis. The shared decision was for the actual standard of care (3, 4) endoscopic combined intrarenal surgery (ECIRS). The MiniECIRS started with flexible ureteroscopy and a posterior calix which gave direct access to the stone was chosen. The tip of the flexible scope was used to mark point A with the C-arm in the 0-degree position and line B in the 90-degree position. Puncture was fast and the MiniECIRS was uneventful with a single mid-pole access guided by the flexible scope. The surgeon had a Full-HD GoPro® camera mounted on his head, controlled by the surgical staff. All essential surgical steps were recorded. Results: The quality of the recorded movie was graded as excellent, and the camera did not cause any discomfort to the surgeon. Operative and X-Ray time were 120minutes and 2minutes (7.64mGy). Hemoglobin drop was 0.8g/dL. The post-operative day-1 computed tomography scan was stone-free. The patient was discharged 24h after surgery. Kidney stent was left with a string and removed after 5days. The patient remained asymptomatic and metabolic evaluation revealed a calcium oxalate stone, low urinary volume and hypocitraturia which were treated with potassium citrate and hydration. Conclusion: The Modified Biplanar (0-90 degree) Endoscopic-Guided Puncture Technique for Percutaneous Nephrolithotomy joins the reproducibility of the same technique under fluoroscopy with advantages regarding safety and efficiency of ECIRS.

Tumors of the chest wall are uncommon lesions that comprise a heterogeneous group of neoplasms. These tumors may arise from osseous structures or soft tissues and may be malignant or benign. We describe the case of a proliferative swelling of uncertain origin that led us to suspect a neuroendocrine origin for the mass we observed and studied. Neuroendocrine tumors arise from neuroendocrine cells, which are peptide- and amine-producing cells dispersed throughout the body. Usually, these tumors occur in various organs as intrathoracic or abdominal masses that become manifest after a variable time, usually after inducing a heterogeneous symptomatology secondary to the secretion of various molecules. The case we describe, on the other hand, develops both exophytically and endophytically, first appearing as an externally developing thoracic mass. Subsequent appropriate investigations revealed bone and muscle involvement in the patient’s thoracic cavity. Therefore, we describe our management of a paucisymptomatic patient who presented with a rapidly developing swelling in the intermammary site that progressed equally rapidly.

IntroductionNon-baumannii Acinetobacter species are increasingly isolated in the clinical setting and the environment. The aim of the present study was to analyze a genome database of 837 Acinetobacter spp. isolates, which included 798 non-baumannii Acinetobacter genomes, in order to define the concordance of classification and discriminatory power of 7-gene MLST, 53-gene MLST, and single-nucleotide polymorphism (SNPs) phylogenies.MethodsPhylogenies were performed on Pasteur Multilocus Sequence Typing (MLST) or ribosomal Multilocus Sequence Typing (rMLST) concatenated alleles, or SNPs extracted from core genome alignment.ResultsThe Pasteur MLST scheme was able to identify and genotype 72 species in the Acinetobacter genus, with classification results concordant with the ribosomal MLST scheme. The discriminatory power and genotyping reliability of the Pasteur MLST scheme were assessed in comparison to genome-wide SNP phylogeny on 535 non-baumannii Acinetobacter genomes assigned to Acinetobacter pittii, Acinetobacter nosocomialis, Acinetobacter seifertii, and Acinetobacter lactucae (heterotypic synonym of Acinetobacter dijkshoorniae), which were the most clinically relevant non-baumannii species of the A. baumannii group. The Pasteur MLST and SNP phylogenies were congruent at Robinson-Fould and Matching cluster tests and grouped genomes into four and three clusters in A. pittii, respectively, and one each in A. seifertii. Furthermore, A. lactucae genomes were grouped into one cluster within A. pittii genomes. The SNP phylogeny of A. nosocomialis genomes showed a heterogeneous population and did not correspond to the Pasteur MLST phylogeny, which identified two recombinant clusters. The antimicrobial resistance genes belonging to at least three different antimicrobial classes were identified in 91 isolates assigned to 17 distinct species in the Acinetobacter genus. Moreover, the presence of a class D oxacillinase, which is a naturally occurring enzyme in several Acinetobacter species, was found in 503 isolates assigned to 35 Acinetobacter species.ConclusionIn conclusion, Pasteur MLST phylogeny of non-baumannii Acinetobacter isolates coupled with in silico detection of antimicrobial resistance makes it important to study the population structure and epidemiology of Acinetobacter spp. isolates.

Abstract Background Wild boar has experienced several evolutionary trajectories from which domestic (under artificial selection) and the feral pig (under natural selection) originated. Strong adaptation deeply affects feral population’s morphology and physiology, including the microbiota community. The gut microbiota is generally recognized to play a crucial role in maintaining host health and metabolism. To date, it is unclear whether feral populations’ phylogeny, development stages or lifestyle have the greatest impact in shaping the gut microbiota, as well as how this can confer adaptability to new environments. Here, in order to deepen this point, we characterized the gut microbiota of feral population discriminating between juvenile and adult samples, and we compared it to the microbiota structure of wild boar and domestic pig as the references. Gut microbiota composition was estimated through the sequencing of the partial 16S rRNA gene by DNA metabarcoding and High Throughput Sequencing on DNA extracted from fecal samples. Results The comparison of microbiota communities among the three forms showed significant differences. The feral form seems to carry some bacteria of both domestic pigs, derived from its ancestral condition, and wild boars, probably as a sign of a recent re-adaptation strategy to the natural environment. In addition, interestingly, feral pigs show some exclusive bacterial taxa, also suggesting an innovative nature of the evolutionary trajectories and an ecological segregation in feral populations, as already observed for other traits. Conclusions The feral pig showed a significant change between juvenile and adult microbiota suggesting an influence of the wild environment in which these populations segregate. However, it is important to underline that we certainly cannot overlook that these variations in the structure of the microbiota also depended on the different development stages of the animal, which in fact influence the composition of the intestinal microbiota. Concluding, the feral pigs represent a new actor living in the same geographical space as the wild boars, in which its gut microbial structure suggests that it is mainly the result of environmental segregation, most different from its closest relative. This gives rise to interesting fields of exploration regarding the changed ecological complexity and the consequent evolutionary destiny of the animal communities involved in this phenomenon.

Abstract Glioblastoma multiforme (GBM) is the most frequent and aggressive form of primary brain tumor in the adult population; its high recurrence rate and resistance to current therapeutics urgently demand a better therapy. Regulation of protein stability by the ubiquitin proteasome system (UPS) represents an important control mechanism of cell growth. UPS deregulation is mechanistically linked to the development and progression of a variety of human cancers, including GBM. Thus, the UPS represents a potentially valuable target for GBM treatment. Using an integrated approach that includes proteomics, transcriptomics and metabolic profiling, we identify praja2, a RING E3 ubiquitin ligase, as the key component of a signaling network that regulates GBM cell growth and metabolism. Praja2 is preferentially expressed in primary GBM lesions expressing the wild-type isocitrate dehydrogenase 1 gene (IDH1). Mechanistically, we found that praja2 ubiquitylates and degrades the kinase suppressor of Ras 2 (KSR2). As a consequence, praja2 restrains the activity of downstream AMP-dependent protein kinase in GBM cells and attenuates the oxidative metabolism. Delivery in the brain of siRNA targeting praja2 by transferrin-targeted self-assembling nanoparticles (SANPs) prevented KSR2 degradation and inhibited GBM growth, reducing the size of the tumor and prolonging the survival rate of treated mice. These data identify praja2 as an essential regulator of cancer cell metabolism, and as a potential therapeutic target to suppress GBM growth.

DNA methylation is an epigenetic modification that plays a pivotal role in major biological mechanisms, such as gene regulation, genomic imprinting, and genome stability. Different combinations of methylated cytosines for a given DNA locus generate different epialleles and alterations of these latter have been associated with several pathological conditions. Existing computational methods and statistical tests relevant to DNA methylation analysis are mostly based on the comparison of average CpG sites methylation levels and they often neglect non-CG methylation. Here, we present EpiStatProfiler, an R package that allows the analysis of CpG and non-CpG based epialleles starting from bisulfite sequencing data through a collection of dedicated extraction functions and statistical tests. EpiStatProfiler is provided with a set of useful auxiliary features, such as customizable genomic ranges, strand-specific epialleles analysis, locus annotation and gene set enrichment analysis. We showcase the package functionalities on two public datasets by identifying putative relevant loci in mice harboring the Huntington’s disease-causing Htt gene mutation and in Ctcf +/− mice compared to their wild-type counterparts. To our knowledge, EpiStatProfiler is the first package providing functionalities dedicated to the analysis of epialleles composition derived from any kind of bisulfite sequencing experiment.

The recent advancements in toxicogenomics have led to the availability of large omics data sets, representing the starting point for studying the exposure mechanism of action and identifying candidate biomarkers for toxicity prediction. The current lack of standard methods in data generation and analysis hampers the full exploitation of toxicogenomics-based evidence in regulatory risk assessment. Moreover, the pipelines for the preprocessing and downstream analyses of toxicogenomic data sets can be quite challenging to implement. During the years, we have developed a number of software packages to address specific questions related to multiple steps of toxicogenomics data analysis and modelling. In this review we present the Nextcast software collection and discuss how its individual tools can be combined into efficient pipelines to answer specific biological questions. Nextcast components are of great support to the scientific community for analysing and interpreting large data sets for the toxicity evaluation of compounds in an unbiased, straightforward, and reliable manner. The Nextcast software suite is available at: ( https://github.com/fhaive/nextcast).

ABSTRACT Purpose: to evaluate the effect of low-calorie diet on 24-hour urinary metabolic parameters of obese adults with idiopathic calcium oxalate kidney stones. Materials and Methods: Adult idiopathic calcium oxalate stone formers, with body mass index (BMI) ≥30kg/m2 and a known lithogenic metabolic abnormality, were submitted to low-calorie diet for twelve weeks. After enrolment, anthropometric measures, serum exams, 24-hour urinary metabolic parameters and body impedance were collected one month prior to dietary intervention and at the end of twelve weeks. Correlations between weight loss, waist circumference loss, fat loss and variation in 24-hour urinary lithogenic parameters and calcium oxalate urinary supersaturation (CaOx SS) as per Tiselius equation were analysed. Results: From January 2017 to January 2018, 39 patients were enrolled to participate in this study. Median (range) prescribed diet was 1300 (1100-2100) Kcal/day. Mean age was 51.7±11.0 (29-68) years old and 69.2% were female. 30.8% of the participants shifted from obesity to BMI

ABSTRACT Purpose: The objective of this study is to evaluate the impact of a previous standard percutaneous nephrolithotomy (PCNL) on the outcomes of retrograde intrarenal surgery (RIRS). Materials and Methods: Outcomes of RIRS performed from January 2017 to January 2020 in adult patients with residual stone fragments ≤20mm after a standard PCNL (Post-PCNL) and symptomatic adult patients with kidney stones ≤20mm (Control) were prospectively studied. Stone-free rate (SFR) was evaluated on a postoperative day 90 non-contrast computed tomography. Surgical complications based on Clavien-Dindo classification during the 90 days of follow-up were recorded. Results: Outcomes of 55 patients and 57 renal units of the post-PCNL group were compared to 92 patients and 115 renal units of the control group. SFR was lower in post-PCNL group than in control (28/57, 49.1% vs. 86/115, 74.8%, p

8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is considered to be a premutagenic DNA lesion generated by 2'-deoxyguanosine (dG) oxidation due to reactive oxygen species (ROS). In recent years, the 8-oxodG distribution in human, mouse, and yeast genomes has been underlined using various next-generation sequencing (NGS)–based strategies. The present study reports the OxiDIP-Seq protocol, which combines specific 8-oxodG immuno-precipitation of single-stranded DNA with NGS, and the pipeline analysis that allows the genome-wide 8-oxodG distribution in mammalian cells. The development of this OxiDIP-Seq method increases knowledge on the oxidative DNA damage/repair field, providing a high-resolution map of 8-oxodG in human cells.

Abstract Background The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena. Results Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs. Conclusions CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs .

Abstract Background and objective: Magnesium ammonium phosphate stones (MAP), also known as struvite stones, are associated with urinary infection and impairment of renal unit. The aim of this study is to evaluate the urinary metabolic risk factors for recurrence of renal calculi in patients submitted to nephrectomy due to MAP stones. Methods: We retrospectively reviewed the charts of patients > 18 years old submitted to total nephrectomy due to pure MAP stones and pure calcium oxalate (CaOx) stones from July 2006 to July 2016. Urinary metabolic parameters were assessed through 24-hour urine exams ≥ 3 months after nephrectomy. Urinary metabolic parameters and new event related to lithiasis were compared. Results: Twenty-eight and 39 patients were included in MAP and CaOx group, respectively. Abnormalities in 24-hour urine samples were similar between groups. Hypercalciuria occurred in 7.1 and 10.3% of patients in MAP and CaOx group, respectively (p = 0.66), whereas hypocitraturia was present in 65.2 and 59.0% of patients with MAP and CaOx group, respectively (p = 0.41). No significant difference in new events was found between MAP and CaOx groups (17.9 vs. 23.1%, respectively; p = 0.60). Conclusion: A 24-hour urine evaluation should be offered to patients submitted to nephrectomy due to pure MAP stones in order to detect metabolic risk, improve treatment, and prevent stone recurrence.

Fetal growth restriction is an obstetrical pathological condition that causes high neonatal mortality and morbidity. The mechanisms of its onset are not completely understood. Metabolites were extracted from 493 placentas from non-complicated pregnancies in Hamilton Country, TN (USA), and analyzed by gas chromatography–mass spectrometry (GC–MS). Newborns were classified according to raw fetal weight (low birth weight (LBW; 2500 g)), and according to the calculated birth weight centile as it relates to gestational age (small for gestational age (SGA), large for gestational age (LGA), and adequate for gestational age (AGA)). Mothers of LBW infants had a lower pre-pregnancy weight (66.2 ± 17.9 kg vs. 73.4 ± 21.3 kg, p < 0.0001), a lower body mass index (BMI) (25.27 ± 6.58 vs. 27.73 ± 7.83, p < 0.001), and a shorter gestation age (246.4 ± 24.0 days vs. 267.2 ± 19.4 days p < 0.001) compared with non-LBW. Marital status, tobacco use, and fetus sex affected birth weight centile classification according to gestational age. Multivariate statistical comparisons of the extracted metabolomes revealed that asparagine, aspartic acid, deoxyribose, erythritol, glycerophosphocholine, tyrosine, isoleucine, serine, and lactic acid were higher in both SGA and LBW placentas, while taurine, ethanolamine, β-hydroxybutyrate, and glycine were lower in both SGA and LBW. Several metabolic pathways are implicated in fetal growth restriction, including those related to the hypoxia response and amino-acid uptake and metabolism. Inflammatory pathways are also involved, suggesting that fetal growth restriction might share some mechanisms with preeclampsia.

The theorem developed by John Bell constituted the starting point of a revolution that translated a philosophical question about the nature of reality into the broad and intense field of research of the quantum information technologies. We focus on a system of two qubits prepared in a random, mixed state, and we study the typical behavior of their nonlocality via the CHSH–Bell inequality. Afterward, motivated by the necessity of accounting for inefficiency in the state preparation, we address to what extent states close enough to one with a high degree of nonclassicality can violate local realism with a previously chosen experimental setup.

Endometrial cancer (EC) is the most common gynecological neoplasm in high-income countries. Five-year survival rates are related to stage at diagnosis, but currently, no validated screening tests are available in clinical practice. The metabolome offers an unprecedented overview of the molecules underlying EC. In this study, we aimed to validate a metabolomics signature as a screening test for EC on a large study population of symptomatic women. Serum samples collected from women scheduled for gynecological surgery (n = 691) were separated into training (n = 90), test (n = 38), and validation (n = 563) sets. The training set was used to train seven classification models. The best classification performance during the training phase was the PLS-DA model (96% accuracy). The subsequent screening test was based on an ensemble machine learning algorithm that summed all the voting results of the seven classification models, statistically weighted by each models’ classification accuracy and confidence. The efficiency and accuracy of these models were evaluated using serum samples taken from 871 women who underwent endometrial biopsies. The EC serum metabolomes were characterized by lower levels of serine, glutamic acid, phenylalanine, and glyceraldehyde 3-phosphate. Our results illustrate that the serum metabolome can be an inexpensive, non-invasive, and accurate EC screening test.

ABSTRACT Objectives Measurements of stone features may vary according to the non-contrast computed tomography (NCCT) technique. Using magnified bone window is the most accurate method to measure urinary stones. Possible differences between stone measurements in different NCCT windows have not been evaluated in stones located in the kidney. The aim of this study is to compare measurements of kidney stone features between NCCT bone and soft tissue windows in patients submitted to retrograde intrarenal surgery (RIRS). Materials and Methods Preoperative and 90th postoperative day NCCT were performed in 92 consecutive symptomatic adult patients (115 renal units) with kidney stones between 5 mm to 20 mm (< 15 mm in the lower calyx) treated by RIRS. NCCT were evaluated in the magnified bone window and soft tissue window in three axes in a different time by a single radiologist blinded for the measurements of the NCCT other method. Results Stone largest size (7.92±3.81 vs. 9.13±4.08; mm), volume (435.5±472.7 vs. 683.1±665.0; mm3) and density (989.4±330.2 vs. 893.0±324.6; HU) differed between bone and soft-tissue windows, respectively (p 2 mm on soft tissue window to 0-2 mm on bone window. Conclusion Kidney stone measurements vary according to NCCT window. Measurements in soft tissue window NCCT of stone diameter and volume are larger and stone density is lesser than in bone window. These differences may have impact on clinical decisions.

ABSTRACT Objective To evaluate the effectiveness and outcomes of endovascular treatment of TRAS with PTA. Materials and Methods We searched our prospectively collected database looking at cases of TRAS between January 2005-December 2011. CCT was the gold-standart for diagnosis of TRAS. Parameters analysed comprised technical aspects, arterial blood pressure variation, and renal function. A minimum follow-up of 24 months was considered. Results Of the 2221 renal transplants performed in the selected period, 22 (0.9%) patients were identified with TRAS. Fourteen (63.6%) were male and mean age was 377±14.8years (12-69). Kidney graft was from deceased donnors in 20 (80%) cases. On doppler evaluation, mean blood flow speed after transplantation, at TRAS diagnosis and after TAP was 210.6±99.5, 417±122.7 and 182.5±81.6mL/sec, respectively (p

Abstract Background Progression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved. Methods We used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets. Results Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens. Conclusions Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer. Graphical abstract

Abstract Background Polycystic ovarian syndrome (PCOS) is a highly variable syndrome and one of the most common female endocrine disorders. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet. Results Fifteen PCOS-patients and 15 controls were enrolled. Patients were treated with myo-inositol (1.75 g/day), D-chiro-inositol (0.25 g/day) and glucomannan (4 g/day) for 3 months. Blood concentrations of glucose, insulin, triglycerides and cholesterol, and ovary volumes and antral follicles count, as well as metabolomic profiles, were evaluated for control subjects and for cases before and after treatment. PCOS-patients had higher BMI compared with Controls, BMI decreased significantly after 3 months of treatment although it remained significantly higher compared to controls. 3-methyl-1-hydroxybutyl-thiamine-diphosphate, valine, phenylalanine, ketoisocapric, linoleic, lactic, glyceric, citric and palmitic acid, glucose, glutamine, creatinine, arginine, choline and tocopherol emerged as the most relevant metabolites for distinguishing cases from controls. Conclusion Our pilot study has identified a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan. Trial registration ClinicalTial.gov, NCT03608813. Registered 1st August 2018 - Retrospectively registered, .

Abstract Background Functional annotation of genes is an essential step in omics data analysis. Multiple databases and methods are currently available to summarize the functions of sets of genes into higher level representations, such as ontologies and molecular pathways. Annotating results from omics experiments into functional categories is essential not only to understand the underlying regulatory dynamics but also to compare multiple experimental conditions at a higher level of abstraction. Several tools are already available to the community to represent and compare functional profiles of omics experiments. However, when the number of experiments and/or enriched functional terms is high, it becomes difficult to interpret the results even when graphically represented. Therefore, there is currently a need for interactive and user-friendly tools to graphically navigate and further summarize annotations in order to facilitate results interpretation also when the dimensionality is high. Results We developed an approach that exploits the intrinsic hierarchical structure of several functional annotations to summarize the results obtained through enrichment analyses to higher levels of interpretation and to map gene related information at each summarized level. We built a user-friendly graphical interface that allows to visualize the functional annotations of one or multiple experiments at once. The tool is implemented as a R-Shiny application called FunMappOne and is available at https://github.com/grecolab/FunMappOne. Conclusion FunMappOne is a R-shiny graphical tool that takes in input multiple lists of human or mouse genes, optionally along with their related modification magnitudes, computes the enriched annotations from Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, or Reactome databases, and reports interactive maps of functional terms and pathways organized in rational groups. FunMappOne allows a fast and convenient comparison of multiple experiments and an easy way to interpret results.

Colorectal cancer (CRC) is a high incidence disease, characterized by high morbidity and mortality rates. Early diagnosis remains challenging because fecal occult blood screening tests have performed sub-optimally, especially due to hemorrhoidal, inflammatory, and vascular diseases, while colonoscopy is invasive and requires a medical setting to be performed. The objective of the present study was to determine if serum metabolomic profiles could be used to develop a novel screening approach for colorectal cancer. Furthermore, the study evaluated the metabolic alterations associated with the disease. Untargeted serum metabolomic profiles were collected from 100 CRC subjects, 50 healthy controls, and 50 individuals with benign colorectal disease. Different machine learning models, as well as an ensemble model based on a voting scheme, were built to discern CRC patients from CTRLs. The ensemble model correctly classified all CRC and CTRL subjects (accuracy = 100%) using a random subset of the cohort as a test set. Relevant metabolites were examined in a metabolite-set enrichment analysis, revealing differences in patients and controls primarily associated with cell glucose metabolism. These results support a potential use of the metabolomic signature as a non-invasive screening tool for CRC. Moreover, metabolic pathway analysis can provide valuable information to enhance understanding of the pathophysiological mechanisms underlying cancer. Further studies with larger cohorts, including blind trials, could potentially validate the reported results.

We present data derived from an exposure experiment in which three cell-lines representative of cell types of the respiratory tissue (epithelial type-I A549, epithelial type-II BEAS-2B, and macrophage THP-1) have been exposed to ten different carbon-based nanomaterials for 48 h.In particular, we provide: genome-wide mRNA and miRNA expression, and DNA methylation; gene tables, containing information on the aberrations induced in these three genomic data layers at the gene level; mechanism of action (MOA) maps representing the comparative functional alteration induced in each cell line and each exposure.

ABSTRACT Introduction: To demonstrate the entire surgeon's point of view of a prone split-leg (PSL) endoscopic guided percutaneous nephrolithotomy (ePCNL) recorded with a GoPro® camera for standardization of the essential technical steps towards a successful procedure (1). Materials and methods: A 40y.o female patient presented with right flank pain for three years. She had previously been submitted to shock wave lithotripsy without success. Non-contrast computed tomography (NCCT) revealed a 2cm stone in the renal pelvis with 1400HU and stone-to-skin distance of 11cm (Guy's Stone Score 1). PCNL approach was chosen for providing higher chances of stone-free after a single procedure. Informed consent was obtained. The PSL ePCNL was uneventful with a single access in a mid-pole. The surgeon had a Full HD GoPro Hero 4® camera mounted on his head, controlled by the surgical staff with a remote control. All essential surgical steps were recorded. Results: Operative time was 90 minutes. Hemoglobin drop was 0.7g/dL. The post-operative NCCT scan was stone-free. The patient was discharged 24h after surgery. Kidney stent was left with a string and removed after 5days. The camera worked properly and didn't cause any kind of discomfort to the surgeon. The quality of the recorded movie was excellent. Conclusion: By recording the surgeon's perspective of an endoscopic urological procedure, we were able to provide a comprehensive understanding of the surgical technique by assembling the endoscopic, fluoroscopic, and operative field views. The GoPro® camera proved to be an interesting tool to document surgical procedures without compromising outcomes and has great potential for educational purposes.

We performed ultra-deep methylation analysis at single molecule level of the promoter region of developmentally regulated D-Aspartate oxidase (Ddo), as a model gene, during brain development and embryonic stem cell neural differentiation. Single molecule methylation analysis enabled us to establish the effective epiallele composition within mixed or pure brain cell populations. In this framework, an epiallele is defined as a specific combination of methylated CpG within Ddo locus and can represent the epigenetic haplotype revealing a cell-to-cell methylation heterogeneity. Using this approach, we found a high degree of polymorphism of methylated alleles (epipolymorphism) evolving in a remarkably conserved fashion during brain development. The different sets of epialleles mark stage, brain areas, and cell type and unravel the possible role of specific CpGs in favoring or inhibiting local methylation. Undifferentiated embryonic stem cells showed non-organized distribution of epialleles that apparently originated by stochastic methylation events on individual CpGs. Upon neural differentiation, despite detecting no changes in average methylation, we observed that the epiallele distribution was profoundly different, gradually shifting toward organized patterns specific to the glial or neuronal cell types. Our findings provide a deep view of gene methylation heterogeneity in brain cell populations promising to furnish innovative ways to unravel mechanisms underlying methylation patterns generation and alteration in brain diseases.

Bladder cancer has a high incidence and is marked by high morbidity and mortality. Early diagnosis is still challenging. The objective of this study was to create a metabolomics-based profile of bladder cancer in order to provide a novel approach for disease screening and stratification. Moreover, the study characterized the metabolic changes associated with the disease. Serum metabolomic profiles were obtained from 149 bladder cancer patients and 81 healthy controls. Different ensemble machine learning models were built in order to: (1) differentiate cancer patients from controls; (2) stratify cancer patients according to grading; (3) stratify patients according to cancer muscle invasiveness. Ensemble machine learning models were able to discriminate well between cancer patients and controls, between high grade (G3) and low grade (G1-2) cancers and between different degrees of muscle invasivity; ensemble model accuracies were ≥80%. Relevant metabolites, selected using the partial least square discriminant analysis (PLS-DA) algorithm, were included in a metabolite-set enrichment analysis, showing perturbations primarily associated with cell glucose metabolism. The metabolomic approach may be useful as a non-invasive screening tool for bladder cancer. Furthermore, metabolic pathway analysis can increase understanding of cancer pathophysiology. Studies conducted on larger cohorts, and including blind trials, are needed to validate results.

Plants emit volatile organic compounds (VOCs) that induce metabolomic, transcriptomic, and behavioral reactions in receiver organisms, including insect pollinators and herbivores. VOCs’ composition and concentration may influence plant-insect or plant-plant interactions and affect soil microbes that may interfere in plant-plant communication. Many Trichoderma fungi act as biocontrol agents of phytopathogens and plant growth promoters. Moreover, they can stimulate plant defense mechanisms against insect pests. This study evaluated VOCs’ emission by olive trees (Olea europaea L.) when selected Trichoderma fungi or metabolites were used as soil treatments. Trichoderma harzianum strains M10, T22, and TH1, T. asperellum strain KV906, T. virens strain GV41, and their secondary metabolites harzianic acid (HA), and 6-pentyl-α-pyrone (6PP) were applied to olive trees. Charcoal cartridges were employed to adsorb olive VOCs, and gas chromatography mass spectrometry (GC-MS) analysis allowed their identification and quantification. A total of 45 volatile compounds were detected, and among these, twenty-five represented environmental pollutants and nineteen compounds were related to olive plant emission. Trichoderma strains and metabolites differentially enhanced VOCs production, affecting three biosynthetic pathways: methylerythritol 1-phosphate (MEP), lipid-signaling, and shikimate pathways. Multivariate analysis models showed a characteristic fingerprint of each plant-fungus/metabolite relationship, reflecting a different emission of VOCs by the treated plants. Specifically, strain M10 and the metabolites 6PP and HA enhanced the monoterpene syntheses by controlling the MEP pathway. Strains GV41, KV906, and the metabolite HA stimulated the hydrocarbon aldehyde formation (nonanal) by regulating the lipid-signaling pathway. Finally, Trichoderma strains GV41, M10, T22, TH1, and the metabolites HA and 6PP improve aromatic syntheses at different steps of the shikimate pathway.

Alterations in the gut microbiome and fecal metabolites have been detected in anorexia nervosa (AN), but differences in those profiles between restricting AN (ANR) and binge-purging AN (ANBP) type have not been explored. We made a secondary analysis of our previous data concerning microbiome and metabolomics profiles of 17 ANR women, six ANBP women and 20 healthy controls (HC). Twelve fecal metabolites differentiating ANR patients, ANBP patients and HC were identified. Both patient groups showed decreased intra-individual bacterial richness with respect to healthy controls (HC). Compared to ANR subjects, ANBP patients had a significant increase in relative abundances of Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, and Eubacteriacae and a significant decrease in relative abundances of Odoribacter, Haemophilus, Pasteurellaceae, and Pasteurellales. The heatmaps of the relationships of selected fecal metabolites with microbial families showed different structures among the three groups, with the heatmap of ANBP patients being drastically different from that of HC, while that of ANR patients resulted more similar to HC. These findings, although preliminary because of the relatively small sample size, confirm the occurrence of different gut dysbiosis in ANR and ANBP and demonstrate different connections between gut microorganisms and fecal metabolites in the two AN types.

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response.

We derive a light–matter interaction Hamiltonian to describe a quantum system embedded in a dispersive environment and coupled with the electromagnetic field. We include in this theory the spatial extension of the system, taken into account through its wavefunction. This enables us to overcome the divergence problem of the Green tensor propagator that arises from a point-like approximation of the quantum system. Thus the formalism can be applied to generalize the expressions for the spontaneous emission rate and the Lamb shift for a quantum system defined by a spatially extended dipole. In particular, these quantities can be modified by the asymmetry of the spatial structure of the atomic system as demonstrated in two test-bed examples.

Main findings A 25-year-old hypertensive female patient was referred to our institution. Initial workup exams demonstrated a 2.8 cm cortical lower pole tumor in the right kidney. She underwent laparoscopic partial nephrectomy without complications. Histopathologic examination revealed a rare juxtaglomerular cell tumor known as reninoma. After surgery, she recovered uneventfully and all medications were withdrawn. Case hypothesis Secondary arterial hypertension is a matter of great interest to urologists and nephrologists. Renovascular hypertension, primary hyperadosteronism and pheocromocytoma are potential diagnosis that must not be forgotten and should be excluded. Although rare, chronic pyelonephritis and renal tumors as rennin-producing tumors, nephroblastoma, hypernephroma, and renal cell carcinoma might also induce hypertension and should be in the diagnostic list of clinicians. Promising future implications Approximately 5% of patients with high blood pressure have specific causes and medical investigation may usually identify such patients. Furthermore, these patients can be successfully treated and cured, most times by minimally invasive techniques. This interesting case might expand knowledge of physicians and aid better diagnostic care in future medical practice.

Multiple myeloma is rare in young patients and may be undiagnosed or characterized by a significant delay in diagnosis. We report the association of stage I myeloma (according to Durie-Salmon classification) and osteoporosis in a 37-year-old male patient complaining of worsening pain in the spine. Pain attacks resulted in increases in blood pressure with hypertensive episodes. The investigations (on the basis of an unclear radiological picture and the presence of hypertensive state) led to the diagnosis of low grade osteoporosis. Since the young subject was symptomatic at the diagnosis, we continued evaluations on the basis of imaging data (DXA) and laboratory tests, revealing the presence of multiple myeloma. Clinical, laboratory, and therapeutic implications of this clinical case are discussed.

This research analyzes the impact of the asymmetry of the quantum system and the range of control possibilities offered by dispersive media and the nanostructures. I investigated the asymmetric behavior of a two level system in the Jaynes-Cummings model (JC) and in the spontaneous emission process discussing respectively the presence of a non trivial emission at the Rabi frequency and the correction at a much more basic level, i.e., in the lifetime of the excited state, and also affect the value of the Lamb shift with broken symmetry in the diagonal terms of dipole moment.

Pediatric obesity-related metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are increasingly frequent conditions with a still-elusive diagnosis and low-efficacy treatment and monitoring options. In this study, we investigated the salivary metabolomic signature, which has been uncharacterized to date. In this pilot-nested case-control study over a transversal design, 41 subjects (23 obese patients and 18 normal weight (NW) healthy controls), characterized based on medical history, clinical, anthropometric, and laboratory data, were recruited. Liver involvement, defined according to ultrasonographic liver brightness, allowed for the allocation of the patients into four groups: obese with hepatic steatosis ([St+], n = 15) and without hepatic steatosis ([St⁻], n = 8), and with (n = 10) and without (n = 13) MetS. A partial least squares discriminant analysis (PLS-DA) model was devised to classify the patients’ classes based on their salivary metabolomic signature. Pediatric obesity and its related liver disease and metabolic syndrome appear to have distinct salivary metabolomic signatures. The difference is notable in metabolites involved in energy, amino and organic acid metabolism, as well as in intestinal bacteria metabolism, possibly reflecting diet, fatty acid synthase pathways, and the strict interaction between microbiota and intestinal mucins. This information expands the current understanding of NAFLD pathogenesis, potentially translating into better targeted monitoring and/or treatment strategies in the future.

Purpose To evaluate infrared thermometer (IRT) accuracy compared to standard digital thermometer in measuring kidney temperature during arterial clamping with and without renal cooling. Materials and Methods 20 pigs weighting 20Kg underwent selective right renal arterial clamping, 10 with (Group 1 - Cold Ischemia with ice slush) and 10 without renal cooling (Group 2 - Warm Ischemia). Arterial clamping was performed without venous clamping. Renal temperature was serially measured following clamping of the main renal artery with the IRT and a digital contact thermometer (DT): immediate after clamping (T0), after 2 (T2), 5 (T5) and 10 minutes (T10). Temperature values were expressed in mean, standard deviation and range for each thermometer. We used the T student test to compare means and considered p < 0.05 to be statistically significant. Results In Group 1, mean DT surface temperature decrease was 12.6 ± 4.1°C (5-19°C) while deep DT temperature decrease was 15.8 ± 1.5°C (15-18°C). For the IRT, mean temperature decrease was 9.1 ± 3.8°C (3-14°C). There was no statistically significant difference between thermometers. In Group 2, surface temperature decrease for DT was 2.7 ± 1.8°C (0-4°C) and mean deep temperature decrease was 0.5 ± 1.0°C (0-3°C). For IRT, mean temperature decrease was 3.1 ± 1.9°C (0-6°C). No statistically significant difference between thermometers was found at any time point. conclusions IRT proved to be an accurate non-invasive precise device for renal temperature monitoring during kidney surgery. External ice slush cooling confirmed to be fast and effective at cooling the pig model. IRT = Infrared thermometer DT = Digital contact thermometer D:S = Distance-to-spot ratio

Purpose to test the effect of stone entrapment on laser lithotripsy efficiency. Materials and Methods Spherical stone phantoms were created using the BegoStone® plaster. Lithotripsy of one stone (1.0g) per test jar was performed with Ho:YAG laser (365µm fiber; 1 minute/trial). Four laser settings were tested: I-0.8J,8Hz; II-0.2J,50Hz; III-0.5J,50Hz; IV-1.5J,40Hz. Uro-Net (US Endoscopy) deployment was used in 3/9 trials. Post-treatment, stone fragments were strained though a 1mm sieve; after a 7-day drying period fragments and unfragmented stone were weighed. Uro-Net nylon mesh and wire frame resistance were tested (laser fired for 30s). All nets used were evaluated for functionality and strength (compared to 10 new nets). Student's T test was used to compare the studied parameters; significance was set at p < 0.05. Results Laser settings I and II caused less damage to the net overall; the mesh and wire frame had worst injuries with setting IV; setting III had an intermediate outcome; 42% of nets were rendered unusable and excluded from strength analysis. There was no difference in mean strength between used functional nets and non-used devices (8.05 vs. 7.45 lbs, respectively; p = 0.14). Setting IV was the most efficient for lithotripsy (1.9 ± 0.6 mg/s; p < 0.001) with or without net stabilization; setting III was superior to I and II only if a net was not used. conclusions Laser lithotripsy is not optimized by stone entrapment with a net retrieval device which may be damaged by high energy laser settings.

CONTEXTPenis size is a great concern for men in many cultures. Despite the great variety of methods for penile augmentation, none has gained unanimous acceptance among experts in the field. However, in this era of minimally invasive procedure, injection therapy for penile augmentation has become more popular. Here we report a case of methacrylate injection in the penis that evolved with penile deformity and sexual dysfunction. This work also reviews the investigation and management of this pathological condition.CASE REPORTA 36-year-old male sought medical care with a complaint of penile deformity and sexual dysfunction after methacrylate injection. The treatment administered was surgical removal. Satisfactory cosmetic and functional results were reached after two months.CONCLUSIONSThere is a need for better structured scientific research to evaluate the outcomes and complication rates from all penile augmentation procedures.CONTEXTOO tamanho peniano é uma grande preocupação para homens em diversas culturas. Apesar da grande variedade de possíveis métodos para o aumento peniano, nenhum ganhou aceitação unânime por especialistas no assunto. Mas na era dos procedimentos minimamente invasivos, a terapia de injeção para aumento peniano tem se tornado mais popular. Aqui relatamos um caso de injeção de metacrilato no pênis que evoluiu com deformidade peniana e disfunção sexual. Este trabalho também revisa a investigação e gerenciamento desta afecção.RELATO DE CASOUm homem de 36 anos procurou atendimento médico com queixa de deformidade peniana e disfunção sexual após injeção de metacrilato. Remoção cirúrgica foi realizada como tratamento. Após dois meses, satisfatórios resultados cosmético e funcional foram alcançados.CONCLUSÃOTrabalhos científicos mais bem estruturados para avaliar as taxas de complicação e resultados de todos os procedimentos para aumento peniano são necessários.

INTRODUCTION: While some studies show that patients submitted to radical nephrectomy have a higher risk of developing chronic kidney disease (CKD), some studies report that carefully selected living kidney donors do not present a higher risk for CKD. Here, we aim to study predictive factors of CKD after radical nephrectomy. MATERIALS AND METHODS: Between January 2006 to January 2010, 107 patients submitted to radical nephrectomy for cortical renal tumors at our institution were enrolled in this study. Demographic data were recorded, modified Charlson-Romano Index was calculated, and creatinine clearance was estimated using abbreviated Modification of Diet in Renal Disease (MDRD) study equation. Pathological characteristics, surgical access and surgical complications were also reviewed. The end-point of the current study was new onset estimated glomerular filtration rate (eGFR) less than 60 and less than 45 mL/minute/1.73 m². RESULTS: Age, preoperative eGFR, Charlson-Romano Index and hypertension were predictive factors of renal function loss, when the end-point considered was eGFR lower than 60 mL/minute/1.73 m². Age and preoperative eGFR were predictive factors of renal function loss, when the end-point considered was eGFR lower than 45 mL/minute/1.73 m². Moreover, each year older increased 1.1 times the risk of eGFR lower than 60 and 45 mL/minute/1.73 m². After multivariate logistic regression, only age remained as an independent predictive factor of eGFR loss. CONCLUSION: Age is an independent predictive factor of GFR loss for patients submitted to radical nephrectomy for cortical renal tumors.

Objective: To present our experience with pancreas retransplantin patients previously submitted to simultaneous pancreas-kidneytransplant, pancreas after kidney transplant and pancreastransplant alone. Methods: Between January/1996 and December/2005, 330 pancreas transplants were performed: 308 primarytransplants and 22 (6%) retransplants of solitary pancreas. Thefollowing variables were analyzed: patient age; time elapsedbetween the first and the second transplant; causes of loss of thefirst graft; technical characteristics of the transplant andretransplant and the criteria for selecting donors for retransplant.These clinical data were submitted to statistical analysis. Results:The mean age of patients was 34.3 years and the mean elapsedtime between the first and second transplant was 19.3 months.The causes of the first graft loss were venous (8; 35%) and arterial(5; 23%) thrombosis, chronic rejection (4; 18%), ischemia/reperfusion injury (2), reflux pancreatitis (1), primary non-function(1) and sepsis (1). A second transplant was performed in thesame iliac fossa in 16 patients (72%). Venous drainage wasperformed in the iliac vein in 16 patients (72%), in the inferior venacava in 5 patients (22%) and in the portal vein in one patient. 6 allbladder drainage was the technique used in 18 (82%) cases andenteric drainage, in 4 patients (18%). Immunosuppressive regimenapplied to all cases was quadruple therapy with antilymphocyteinduction, tacrolimus, mycophenolate mofetil and steroids. Therewas one early death due to sepsis. One-year patient and pancreasgraft survival rates for retransplants were, respectively, 95% and85%. There was no additional risk for removing the pancreas graftat retransplant. Conclusion: Pancreas retransplant was technicallyfeasible in all cases and results similar to those described in theliterature were found for primary pancreas transplant.

The regions surrounding transcription start sites (TSSs) of genes play a critical role in the regulation of gene expression. At the same time, current evidence indicates that these regions are particularly stressed by transcription-related mutagenic phenomena. In this work we performed a genome-wide analysis of the distribution of single nucleotide polymorphisms (SNPs) inside the 10 kb region flanking human TSSs by dividing SNPs into four classes according to their frequency (rare, two intermediate classes, and common). We found that, in this 10 kb region, the distribution of variants depends on their frequency and on their localization relative to the TSS. We found that the distribution of variants is generally different for TSSs located inside or outside of CpG islands. We found a significant relationship between the distribution of rare variants and nucleosome occupancy scores. Furthermore, our analysis suggests that evolutionary (purifying selection) and nonevolutionary (biased gene conversion) forces both play a role in determining the relative SNP frequency around TSSs. Finally, we analyzed the potential pathogenicity of each class of variant using the Combined Annotation Dependent Depletion score. In conclusion, this study provides a novel and detailed view of the distribution of genomic variants around TSSs, providing insight into the forces that instigate and maintain variability in such critical regions.

Objetivo: O transplante de pâncreas constitui o único método capaz de restabelecer por completo o controle glicêmico sem o uso de insulina exógena. A drenagem exócrina do enxerto pancreático permanece em discussão. O objetivo desse relato é expor o caso de transplante de pâncreas e rim simultâneo com drenagem entérica submetido à cirurgia de conversão para drenagem vesical, com boa evolução após fístula duodeno-entérica. Método e Critério: Paciente de 36 anos do sexo feminino, portadora de diabetes mellitus tipo I há 23 anos, foi submetida ao transplante de pâncreas e rim simultâneo com drenagem entérica. Houve boa evolução inicial, mas evoluiu com fístula duodenal. Foi submetida a duas intervenções cirúrgicas, sendo que, na segunda, realizou-se conversão para drenagem vesical com sucesso. Discussão e Conclusão: A opção cirúrgica de conversão de drenagem entérica para vesical após o transplante de pâncreas é factível em casos nos quais o risco gerado ao paciente seja compensatório. São potencialmente elegíveis para esse procedimento pacientes com fístulas entéricas após transplante duplo com drenagem entérica.

INTRODUCTION:: To demonstrate the entire surgeon's point of view of a prone split-leg (PSL) endoscopic guided percutaneous nephrolithotomy (ePCNL) recorded with a GoPro® camera for standardization of the essential technical steps towards a successful procedure (1). MATERIALS AND METHODS:: A 40y.o female patient presented with right flank pain for three years. She had previously been submitted to shock wave lithotripsy without success. Non-contrast computed tomography (NCCT) revealed a 2cm stone in the renal pelvis with 1400HU and stone-to-skin distance of 11cm (Guy's Stone Score 1). PCNL approach was chosen for providing higher chances of stone-free after a single procedure. Informed consent was obtained. The PSL ePCNL was uneventful with a single access in a mid-pole. The surgeon had a Full HD GoPro Hero 4® camera mounted on his head, controlled by the surgical staff with a remote control. All essential surgical steps were recorded. RESULTS:: Operative time was 90 minutes. Hemoglobin drop was 0.7g/dL. The post-operative NCCT scan was stone-free. The patient was discharged 24h after surgery. Kidney stent was left with a string and removed after 5days. The camera worked properly and didn't cause any kind of discomfort to the surgeon. The quality of the recorded movie was excellent. CONCLUSION:: By recording the surgeon's perspective of an endoscopic urological procedure, we were able to provide a comprehensive understanding of the surgical technique by assembling the endoscopic, fluoroscopic, and operative field views. The GoPro® camera proved to be an interesting tool to document surgical procedures without compromising outcomes and has great potential for educational purposes.

ABSTRACT Purpose: To assess the public hospitalization rate due to stone disease in a large developing nation for a 15-year period and its association with socio-demographic data. Materials and Methods: A retrospective database analysis of hospitalization rates in the Brazilian public health system was performed, searching for records with a diagnosis code of renal/ureteral calculi at admission between 1998–2012. Patients managed in an outpatient basis or private care were excluded. Socio-demographic data was attained and a temporal trend analysis was performed. Results: The number of stone-related hospitalizations increased from 15.7%, although the population-adjusted hospitalization rate remained constant in 0.04%. Male:female proportion among hospitalized patients was stable (49.3%:50.7% in 1998; 49.2%:50.8% in 2012), though there was a significant reduction in the prevalence of male hospitalizations (−3.8%;p=0.041). In 2012, 38% of hospitalized patients due to stone disease had 40–59 years-old. The ≥80 years-old strata showed the most significant decrease (−43.44%;p=0.022), followed by the 20–39 (−23.17%;p