Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium)

Purpose To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Delta 1 = POD-1 eGFR - baseline eGFR; Delta 2 = 6 months eGFR - POD-1 eGFR; Delta 3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by >= 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. Results A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ss 9.2 +/- 0.7, p < 0.001) during follow-up. Conclusion Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC

ESCRT ubiquitin-binding domains function cooperatively during MVB cargo sorting

Ubiquitin (Ub) sorting receptors facilitate the targeting of ubiquitinated membrane proteins into multivesicular bodies (MVBs). Ub-binding domains (UBDs) have been described in several endosomal sorting complexes required for transport (ESCRT). Using available structural information, we have investigated the role of the multiple UBDs within ESCRTs during MVB cargo selection. We found a novel UBD within ESCRT-I and show that it contributes to MVB sorting in concert with the known UBDs within the ESCRT complexes. These experiments reveal an unexpected level of coordination among the ESCRT UBDs, suggesting that they collectively recognize a diverse set of cargo rather than act sequentially at discrete steps

Development of Polyamide 6 (PA6)/Polycaprolactone (PCL) Thermoplastic Self-Healing Polymer Blends for Multifunctional Structural Composites

High-performance composites suffer from fatigue crack propagation during service. Traditional repair methods can be expensive and time-consuming. Therefore, research on composites with self-healing capabilities has considerably increased in the past decade. The aim of this work is to develop a polyamide 6 (PA6) matrix with self-healing properties. Polycaprolactone (PCL) was used as healing agent and melt compounded with PA6. PCL caused a decrease of the mechanical properties of PA6, due to its immiscibility and low mechanical properties. Nevertheless, acceptable fracture toughness values in quasi-static mode were obtained. Samples were thermally mended at 80 and 100 °C, and the healing efficiency was assessed by comparing the fracture toughness of virgin and repaired samples both in quasi-static and in impact mode. The blend with a PCL content of 30 wt% showed limited healing efficiency values (up to 6%) in quasi-static mode, while an interesting repair capability (53%) was detected under impact conditions. This discrepancy was explained through microstructural analysis and correlated to a different fracture morphology. In fact, under quasi-static mode, the PA6 matrix was severely plasticized, while under impact a brittle fracture surface was obtained. This morphology favored the flow of PCL during the thermal healing process

Development of a microfabrication technology for microcantilever-based detection modules in Lab-On-a-Chip application

Nowadays, the development of Lab-On-a-Chip (LOC) technologies has opened up new perspectives in the field of personalized diagnosis and treatment, by taking advantage of reduced size, low volume requirement for samples, and rapid analysis. In particular, MEMS, microelectronics and nanobiotechnology are enabling technologies for the realization of biosensors by combining both microsystems for sample handling, signal read-out and functionalization methodologies able to detect specific bioaffinity reactions. In this frame, LOC technologies are a powerful tool to perform a wide range of proteomic and genomic tests starting from fluid biological samples such as blood or saliva. In this work we present the design and realization of the first prototypes for testing a technology for LOC detection module for pre-screenings of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis in point-of-care applications. This module is based on arrays of silicon microcantilevers, which are typically suspended beams realised with MEMS fabrication technologies, suitable for biological and chemical sensing. Sensitivity to specific analytes can be achieved by coating the beam surface with proper films, able to selectively bind a particular target molecule. A self assembled monolayer (SAM) of known ss-DNA probes will represent the functional layer. The following hybridization of the complementary target sequence induces a differential stress between the top and the bottom surfaces of a cantilever, driving the deflection of the beam. The proposed technological approach is based on the fabrication of microcantilevers starting from Silicon-On-Insulator (SOI) substrates, allowing an extreme reduction in the thickness of the beams (380 nm), parameter that is related to the sensitivity of the overall biosensor. Both analytical and finite element analysis have been performed, focused on the general validation of the approach and on the design optimization respectively. Preliminary results on the fabrication and testing will be also highlighted

A multiparametric electrochemical microsensor for wine yeast quality assessment

This work is aimed at the realization of an integrated platform for high-throughput screening of wine yeast strains in order to improve the overall quality and productivity of wine making process. The approach is based on a multiparametric sensors integrated with a non-standard fabrication process derived from a 4µm Al-gate CMOS technology, allowing the on-line monitoring of pH, temperature and impedance of yeast cultures for the characterization of ethanol resistance of yeasts

Micro-Id-Gym: Identity Management Workouts with Container-Based Microservices

Identity Management (IdM) solutions are increasingly important for building trust in current and future digital ecosystems. Unfortunately, not only their secure deployment but even their usage are non-trivial activities that require a good level of security awareness. For this, we introduce Micro-Id-Gym, an easy to configure training environment in which users can develop hands-on experiences on how IdM solutions work and better understand the underlying security issues

Necrotrophic fungal plant pathogens display different mechanisms to counteract grape chitinase and thaumatin-like protein

We characterized the ability of the necrotrophic plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Sclerotinia minor and Sclerotium rolfsii to degrade or sequester two widespread plant PR proteins: a type IV chitinase and a thaumatin-like protein (TLP). A protein (150 mg mL1) extract from grape berries, containing about 58 and 68 mg mL1 of TLP and chitinase, respectively, was added to the fungal cultures. The growth of the four fungi was not negatively affected by these proteins and, as determined by RPHPLC, both TLP and chitinase were partially removed from the medium by the three ascomycetes fungi and almost completely by the basidiomycete S. rolfsii. Different levels of protease activity were secreted by fungi but these activities were ineffective against TLP and only partially active against chitinase. The cleavage of chitinase by B. cinerea protease generated a characteristic lower molecular size band on SDS-PAGE. To verify a possible absorption of TLP and chitinase by the fungal talli, mycelia were treated with b-1,3- glucanase. TLP and, to a lower extent, chitinase were released from mycelium of the three ascomycetes fungi but not from that of S. rolfsii. The treatment with b-1,3-glucanase of a mixture containing PR proteins and a purified preparation of the S. rolfsii glucan did not release TLP or chitinase. However, the two proteins were observed when the mixture was analyzed on SDS-PAGE. This result indicates a different type of binding of PR proteins with the glucan matrix of S. rolfsii in comparison to that of the three ascomycetes. As determined by RT-qPCR, one of the two examined putative glucan synthase genes of S. rolfsii was up-regulated following the administration of PR proteins, suggesting the formation of new glucan. Overall, in comparison to protease activity, the sequestering capacity of the fungal glucan matrix seems to play a major role in the fungal defense against the plant TLP and chitinase