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In the past decade, scientific research in the area of Nephrology has focused on evaluating the clinical utility and performance of various biomarkers for diagnosis, risk stratification and prognosis. Before implementing a biomarker in everyday clinical practice for screening a specific disease context, specific statistic measures are necessary to evaluate the diagnostic accuracy and performance of this biomarker. Receiver Operating Characteristic (ROC) Curve analysis is an important statistical method used to estimate the discriminatory performance of a novel diagnostic test, identify the optimal cut-off value for a test that maximizes sensitivity and specificity, and evaluate the predictive value of a certain biomarker or risk, prediction score. Herein, through practical examples, we aim to present a simple methodological approach to explain in detail the principles and applications of ROC curve analysis in the field of nephrology pertaining diagnosis and prognosis., (© 2024. The Author(s).)

Background: Neuropeptide Y (NPY) is a neurotransmitter expressed in both the central and peripheral nervous systems, which is involved in regulating a multitude of physiological processes ranging from arterial pressure, energy balance, the immune response and inflammation and renal electrolyte transport. In a cohort of chronic kidney disease (CKD) patients, we recently showed that high plasma NPY levels predict renal disease progression independently of hypertension and other risk factors but the causal nature of this association remains unproven., Methods: In the same cohort of the previous study, we tested the relationship of NPY gene variability, as assessed by five single nucleotide polymorphisms (SNPs) that explained the whole gene variability, with the incidence rate of a predefined combined renal endpoint (dialysis/transplantation/estimated glomerular filtration rate reduction >30%) over a median follow up of 36 months (inter-quartile range 35-37 months) in 735 ethnically homogeneous patients with stage 2-5 CKD., Results: Two variants [rs16131 (recessive model for the T risk allele: TT, n  = 563; CT + CC, n  = 172) and rs16140 (dominant model for the G risk allele: GG + CG, n  = 413; CC, n  = 322)] were coherently associated with the incidence rate of renal events [hazard ratio (HR) ranging from 1.39 to 1.57, P  ≤ 0.015] and this was also true when the two SNPs were jointly introduced into the same Cox model ( P  ≤ 0.043). The analysis of the biological interaction showed a significant synergism between the NPY rs16131 and rs16140 variants. Indeed, patients harboring NPY rs16131 TT and NPY rs16140 GG + CG risk genotypes had a much higher HR of renal events [HR: 1.80, 95% confidence interval (CI):1.16-2.79, P  = 0.009] than that expected in the absence of biological interaction under both the additive and multiplicative models and the attributable proportion due to interaction (AP) was 25% and 38% on crude and adjusted analyses, respectively., Conclusion: This study, based on the Mendelian randomization approach and using NPY gene variants as instrumental variables to test the link between NPY and CKD progression, is in line with findings indicating that high plasma NPY levels predict an increased risk for renal events and lend support to the hypothesis that NPY is causally involved in renal disease progression., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Exosomes mediate near and long-distance intercellular communication by transferring their molecular cargo to recipient cells, altering their biological response. Milk exosomes (MEx) are internalized by immune cells and exert immunomodulatory functions in vitro. Porcine MEx can accumulate in the small intestine, rich in macrophages. No information is available on the immunomodulatory ability of porcine MEx on porcine monocytes, which are known precursors of gut macrophages. Therefore, this study aims at (1) assessing the in vitro uptake of porcine MEx by porcine monocytes (CD14+), and (2) evaluating the in vitro impact of porcine MEx on porcine monocytes immune functions. MEx were purified by ultracentrifugation and size exclusion chromatography. The monocytes' internalization of PKH26-labeled MEx was examined using fluorescence microscopy. Monocytes were incubated with increasing exosome concentrations and their apoptosis and viability were measured. Lastly, the ability of MEx to modulate the cells' immune activities was evaluated by measuring monocytes' phagocytosis, the capacity of killing bacteria, chemotaxis, and reactive oxygen species (ROS) production. MEx were internalized by porcine monocytes in vitro. They also decreased their chemotaxis and phagocytosis, and increased ROS production. Altogether, this study provides insights into the role that MEx might play in pigs' immunity by demonstrating that MEx are internalized by porcine monocytes in vitro and exert immunomodulatory effects on inflammatory functions., (© 2023. The Author(s).)

In this paper, we present a mechanical hand-tracking system with tactile feedback designed for fine manipulation in teleoperation scenarios. Alternative tracking methods based on artificial vision and data gloves have become an asset for virtual reality interaction. Yet, occlusions, lack of precision, and the absence of effective haptic feedback beyond vibrotactile still appear as a limit for teleoperation applications. In this work, we propose a methodology to design a linkage mechanism for hand pose tracking purposes, preserving complete finger mobility. Presentation of the method is followed by design and implementation of a working prototype, and by evaluation of the tracking accuracy using optical markers. Moreover, a teleoperation experiment involving a dexterous robotic arm and hand was proposed to ten participants. It investigated the effectiveness and repeatability of the hand tracking with combined haptic feedback during a proposed pick and place manipulation tasks.

Background: Metabolic acidosis accelerates chronic kidney disease (CKD) progression towards kidney failure in animal models. Clinical trials testing the effect of bicarbonate on kidney outcomes are underpowered and/or of suboptimal quality. On the other hand, observational studies testing the same hypothesis are generally based on bicarbonate measured at a single time point., Methods: We studied the longitudinal relationship between repeated venous bicarbonate levels and a predefined composite renal outcome (a ≥30% estimated glomerular filtration rate reduction, dialysis or transplantation) by using group-based trajectory model (GBTM) analysis. The GBTM analysis was used to classify patients based on individual bicarbonate levels over time. The relationship between trajectory groups and renal outcomes was investigated using crude and adjusted Cox regression models. A total of 528 patients with stage 2-5 CKD were included in the analysis., Results: The GBTM analysis identified four distinct trajectories of bicarbonate levels: low, moderate, moderate-high and high. During the follow-up period, 126 patients experienced the combined renal endpoint. The hazard rate of renal events decreased dose-dependently from the lowest to the highest bicarbonate trajectory. After adjusting for potential confounders, there was a 63% risk reduction for the composite renal endpoint for patients in the high trajectory category compared with those in the low trajectory category., Conclusion: The study found that higher bicarbonate trajectories were associated with a lower risk of adverse renal outcomes in CKD patients. These results suggest that strategies to maintain higher bicarbonate levels may benefit patients with CKD. However, further high-quality randomised trials are needed to confirm these findings and recommend bicarbonate supplementation as a strategy to delay CKD progression., Competing Interests: C.Z. is a member of the CKJ editorial board. No conflicts of interest are related to this paper as for the remaining co-authors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Sex differences for cardiovascular (CV) risk and outcomes in chronic kidney disease (CKD) patients not on dialysis have been scarcely or never investigated. We therefore studied this important aspect in a cohort of CKD stage 2-5 in the south of Italy., Methods: We tested the relationship between sex and fatal and non-fatal major CV events in a cohort of 759 stage 2-5 CKD patients followed up for a median time of 36 months., Results: Out of 759 patients, 455 were males (60%) and the remaining 304 patients were females (40%). During the follow-up, 42 patients died, and 118 had fatal and non-fatal CV events. On univariate Cox regression analyses, the male sex failed to be associated with all-cause mortality but was strongly related to the incidence rate of fatal and non-fatal major CV events [hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.18-2.60, P  = .006]. Data adjustment for a series of major potential confounders did not materially affect the strength of this relationship (HR 1.78, 95% CI 1.03-3.09). Further analysis testing the effect of age on major CV outcomes by sex showed an effect modification by this risk factor on the same outcome ( P  = .037) because the HR of male versus female CV events increased progressively with aging., Conclusion: Male patients in stage G2-5 CKD had a higher risk for CV events compared with female patients. Age was shown to be a risk modifier for the association between sex and CV events and this risk increased linearly across a wide age spectrum in CKD patients., Competing Interests: C.Z. and F.M. are members of the CKJ editorial board., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

We present a novel soft exoskeleton providing active support for hand closing and opening. The main novelty is a different tendon routing, folded laterally on both sides of the hand, and adding clenching forces when the exoskeleton is activated. It improves the stability of the glove, diminishing slippage and detachment of tendons from the hand palm toward the grasping workspace. The clenching effect is released when the hand is relaxed, thus enhancing the user's comfort. The alternative routing allowed embedding a single actuator on the hand dorsum, resulting more compact with no remote cable transmission. Enhanced adaptation to the hand is introduced by the modular design of the soft polymer open rings. FEM simulations were performed to understand the interaction between soft modules and fingers. Different experiments assessed the desired effect of the proposed routing in terms of stability and deformation of the glove, evaluated the inter-finger compliance for non-cylindrical grasping, and characterized the output grasping force. Experiments with subjects explored the grasping performance of the soft exoskeleton with different hand sizes. A preliminary evaluation with Spinal Cord Injury patients was useful to highlight the strengths and limitations of the device when applied to the target scenario.

Background: Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) have been implicated in CKD progression in follow-up studies focusing on single measurements of individual biomarkers made at baseline only. The simultaneous relationship between the time trend of these biomarkers over the course of CKD and renal outcomes has never been tested., Methods: We applied the joint model (JM) to investigate the longitudinal relationship between repeated measurements of CKD-MBD biomarkers and a combined renal endpoint (estimated glomerular filtration rate reduction >30%, dialysis or transplantation) in 729 stage 2-5 CKD patients over a 36-month follow-up., Results: In the survival submodel of the JM, the longitudinal series of parathyroid hormone (PTH) values was directly and independently related to the risk of renal events [hazard ratio (HR) (1 ln increase in parathyroid hormone (PTH) 2.0 (range 1.5-2.8), P < .001)] and this was also true for repeated measurements of serum phosphate [HR (1 mg/dl) 1.3924 (range 1.1459-1.6918), P = .001], serum calcium [HR (1 mg/dl) 0.7487 (range 0.5843-0.9593), P = .022], baseline fibroblast growth factor 23 [HR (1 pg/ml) 1.001 (range 1.00-1.002), P = .045] and 1,25-dihydroxyvitamin D [HR (1 pg/ml) 0.9796 (range 0.9652-0.9942), P = .006]., Conclusion: Repeated measurements of serum PTH, calcium and phosphate as well as baseline FGF23 and 1,25-dihydroxyvitamin D are independently related with the progression to kidney failure in a cohort of stage 2-5 CKD patients. This longitudinal study generates the hypothesis that interventions at multiple levels on MBD biomarkers can mitigate renal function loss in this population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Endothelial dysfunction (ED) starts early in chronic kidney disease (CKD) and is the hallmark of atherosclerosis in these patients. During recent years, numerous markers have emerged, aiming to predict the onset of ED in CKD patients. Therefore, there is a need to evaluate and assess the discriminatory ability (or diagnostic accuracy) of such a marker (i.e., the ability to correctly classify individuals as having a given disease or not) and identify the optimal cut-off value. A receiver operating characteristic (ROC) curve analysis has been used in the majority of the research papers evaluating the predictive ability of a marker of ED. It is a graphical plot combining pairs of sensitivity (true positive rate) on the y axis and the complement of specificity (1-specificity, false positive rate) in the x axis, corresponding to several of the cut-off values covering the complete range of possible values that this test/marker might take. Herein, using a series of practical examples derived from clinical studies on ED in the special population of CKD, we address the principles, fundamentals, advantages and limitations regarding the interpretation of the ROC analysis.

Objective: The purpose of the current study is to use 3D technology to measure in-vehicle belt fit both with and without booster seats across different vehicles among a large, diverse sample of children and to compare belt fit with and without a booster., Methods: Lap and shoulder belt fit were measured for 108 children ages 6-12 years sitting in the second-row, outboard seats of three vehicles from October 2017 to March 2018. Each child was measured with no booster, a backless booster, and a high-back (HB) booster in three different vehicles. Alternative high-back (HB HW) and backless boosters that could accommodate higher weights were used for children who were too large to fit in the standard boosters. Lap and torso belt scores were computed based on the belt location relative to skeletal landmarks., Results: Both lap and torso belt fit scores were significantly different across vehicles when using the vehicle belt alone (no booster). In all vehicles, lap belt fit improved when using boosters compared with no booster among children ages 6-12 years in rear seats-with one exception of the HB HW booster in the minivan. Torso belt fit improved when using boosters compared with no booster in the sedan, and torso belt fit improved in the minivan and SUV with the use of HB and HB HW boosters when compared with no booster., Conclusions: Lap and torso belt fit for children ages 6-12 years in rear seats was substantially improved by using boosters. Parents and caregivers should continue to have their children use booster seats until vehicle seat belts fit properly which likely does not occur until children are 9-12 years old. Decision makers can consider strengthening child passenger restraint laws with booster seat provisions that require children who have outgrown car seats to use booster seats until at least age 9 to improve belt fit and reduce crash injuries and deaths.

Objective: Teen drivers experience elevated crash risk compared with experienced adult drivers. Active parental oversight can improve teen driving safety, and several manufacturers have released teen-focused safety features over the past decade. Still, parents don't always use these systems and often don't even know their vehicle is equipped. A recent survey found that parents who do know about such systems on their vehicle first learned of them from a salesperson at a dealership. The current study examined how salespeople discuss and sell teen-specific safety systems on vehicles to parents shopping for a new teen driver., Methods: The study focused on four vehicle brands. Two researchers posed as the parents of a new teen driver who were shopping for a vehicle for their teen. They entered dealerships and conducted semistructured interviews with the salesperson that approached them, using prompts of increasing specificity about their teen driver and their interest in safety, and tracking at what point each salesperson mentioned their brand's teen-specific systems, what features they mentioned, and how accurate those mentions were., Results: Thirty of the 40 participating salespeople were able to mention their brand's teen-specific system at some point during the procedure. Hyundai salespeople most consistently brought up their brand's teen features, and Chevy salespeople mentioned the most features while Ford salespeople mentioned the fewest. Salespeople often mentioned speed-related features, although the most commonly mentioned features varied by brand. No participating salespeople reported receiving training specifically about their brand's teen features., Discussion: Most salespeople approached did mention their brand's teen-focused safety systems, but did not usually do so until they had received more targeted prompts. Information these salespeople did share was often vague and general. Salespeople are a key source of information about a vehicle's specific and relevant safety features, and parents without at least some vague preexisting knowledge about the systems or features that could be available on a vehicle of interest are not likely to leave a dealership with a clear idea of all available features that could aid their efforts to keep their teen drivers safe.