Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant

Background A long-standing effort is dedicated towards the identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant. Methods We characterized 37 surface antigens by flow cytometry, in serum and urine EVs from 58 patients who were evaluated before, and at 10-14 days, 3 months and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year. Results Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated with patient outcome at univariate analysis and were able to predict patient outcome at receiver operating characteristics curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome. Conclusions An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis

Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl4) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl4 administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI

[Transcatheter mitral valve repair for patients not amenable to surgical correction: epidemiology, diagnosis, equiti of access, and economic impact]

Mitral regurgitation is the most common valvular heart disease in western world, with moderate to severe mitral regurgitation having a deep impact on prognosis, mortality and rehospitalizations. Advanced congestive heart failure is frequently complicated by mitral regurgitation, a pathologic condition that is often under-diagnosed. A significant proportion of patients with severe mitral regurgitation is not eligible for surgery (mitral valve repair or replacement) because of contraindications or excessive surgical risk. Therefore, the need for a less invasive treatment has led to the development of endovascular techniques; among them the MitraClip system, which mimics Alfieri's edge-to-edge surgical technique introduced in 2003, has gained widespread acceptance. More than 35 000 patients have been treated using this technique. Evidence from clinical studies suggests that the MitraClip system is effective in improving survival and quality of life in patients with severe mitral regurgitation, also reducing rehospitalization rates with substantial social and economic advantages. At present, in Italy, undertreatment of patients with severe mitral regurgitation not amenable to surgical correction is still significantly high, and remarkable inhomogeneity among regions is observed in the availability of the MitraClip procedure

Dialyzability of Oxycodone and Its Metabolites in Chronic Noncancer Pain Patients with End-Stage Renal Disease

Objectives: Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking. Methods: We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis. Results: Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. Discussion: While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future

[Updated SICI-GISE position paper on institutional and operator requirements for transcatheter aortic valve implantation]

Transcatheter aortic valve implantation (TAVI) has revolutionized the management of patients with symptomatic severe aortic stenosis and has become the standard of care for inoperable patients and the preferred therapy for those at increased surgical risk with peculiar clinical and anatomic features. Technology advances, growing experience and accumulating data prompted the update of the 2011 Italian Society of Interventional Cardiology (SICI-GISE) position paper on institutional and operator requirements to perform TAVI. The main objective of this document is to provide a guidance to assess the potential of institutions and operators to initiate and maintain an efficient TAVI program