Protein Complexes in Urine Interfere with Extracellular Vesicle Biomarker Studies

Urine exosomes (extracellular vesicles; EVs) contain (micro)RNA (miRNA) and protein biomarkers that are useful for the non-invasive diagnosis of various urological diseases. However, the urinary Tamm-Horsfall protein (THP) complex, which forms at reduced temperatures, may affect EV isolation and may also lead to contamination by other molecules including microRNAs (miRNAs). Therefore, we compared the levels of three miRNAs within the purified EV fraction and THP- protein-network. Urine was collected from healthy donors and EVs were isolated by ultracentrifugation (UC), two commercial kits or sepharose size-exclusion chromatography (SEC). SEC enables the separation of EVs from protein-complexes in urine. After UC, the isolation of EV-miRNA was compared with two commercial kits. The EV isolation efficiency was evaluated by measuring the EV protein markers, Alix and TSG101, CD63 by Western blotting, or miR-375, miR-204 and miR-21 by RT-qPCR. By using commercial kits, EV isolation resulted in either low yields or dissimilar miRNA levels. Via SEC, the EVs were separated from the protein-complex fraction. Importantly, a different ratio was observed between the three miRNAs in the protein fraction compared to the EV fraction. Thus, protein-complexes within urine may influence EV-biomarker studies. Therefore, the characterization of the isolated EV fraction is important to obtain reproducible results

Wordt stedelijk waterbeheer steeds duurzamer?

De kennis over stedelijk waterbeheer heeft de afgelopen decennia een grote vlucht genomen. Maar dat dit nog geen garantie voor duurzaam stedelijk waterbeheer biedt, was goed terug te zien op het congres over dit onderwerp in Porto Alegre (Brazilië). Inzicht hebben in de effecten van klimaatverandering is nog maar een eerste stap naar steden, die voldoende beschermd zijn voor overstromingen, en gezond water bieden aan hun inwoners. Ervaringsuitwisseling van stedelijk waterdeskundigen van over de hele wereld helpt daar in ieder geval bij

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

Introduction. A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods. Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg j1 of fluvoxamine. Analysis. With increasing dose a disproportional increase in brain concentrations was observed. Th

Implementation of the Participatory Approach for Supervisors to Increase Self-Efficacy in Addressing Risk of Sick Leave of Employees:Results of a Cluster-Randomized Controlled Trial

Purpose To study the effectiveness of a multifaceted strategy to implement the participatory approach (PA) for supervisors to increase their self-efficacy in addressing risk of sick leave of employees. Methods Supervisors from three organizations were invited to participate. Randomization was performed at department level. Supervisors (n = 61) in the intervention departments received the implementation strategy consisting of a working group meeting, supervisor training in PA application, and optional supervisor coaching. Supervisors in the control departments (n = 55) received written information on PA. The primary outcome was supervisors' self-efficacy to apply the PA, measured at baseline and 6 months' follow-up. The number of employees with whom supervisors discussed work functioning problems or (risk of) sick leave was also assessed. Effects were tested using multilevel analyses. Results The strategy did not increase self-efficacy to apply the PA. Subgroup analyses showed that self-efficacy increased for supervisors who at baseline reported to have discussed (risk of) sick leave with less than three employees during the last 6 months (B = 1.42, 95 % CI 0.34-2.50). Furthermore, the implementation strategy increased the number of employees with whom supervisors discussed work functioning problems or risk of sick leave (B = 1.26, 95 % CI 0.04-2.48). Conclusion Although the implementation strategy cannot be recommended for all supervisors, for supervisors who less frequently discuss (risk of) sick leave with employees the implementation strategy might be helpful. Trial registration NTR3733

Employees' Perceptions of Social Norms as a Result of Implementing the Participatory Approach at Supervisor Level:Results of a Randomized Controlled Trial

Purpose A multifaceted implementation strategy was targeted at supervisors to encourage them to apply a participatory approach (PA) in dealing with employees’ work functioning problems due to health concerns. This paper assesses the effect on employees’ perceived social norms regarding the use of the PA to deal with work functioning problems. Methods Three organizations participated in a cluster randomized controlled trial, with randomization at the department level. Supervisors in the PA intervention departments received the implementation strategy consisting of a working group meeting, supervisor training, and optional coaching. Supervisors in the control departments received written information about the PA only. In two of the organizations, employees were invited to complete surveys at baseline and at 6-month follow-up. The primary outcome was perceived social norms regarding the use of the PA to deal with work functioning problems. Secondary measures included attitudes and self-efficacy, and intention regarding joint problem solving, and sick leave data. Effects were analyzed using multilevel analyses to account for nesting of cases. Results At baseline, 273 employees participated in the survey, with follow-up analyses of 174 employees. There were no statistically significant group effects on employee outcome measures. The intervention group showed a larger reduction in mean sick days (from 4.6 to 2.4 days) versus the control group (from 3.8 to 3.6 days), but this difference did not reach statistical significance (p > .05). Conclusion The multifaceted strategy to implement the participatory approach for supervisors did not show effects on outcomes at the employee level. To gain significant effects at the employee level, may require that an implementation strategy not only targets management and supervisors, but also employees themselves. Trial registration: NTR3733

Hortus Medicus Et Philosophicus : In Quo Plurimarum Stirpium Breues Descriptiones, Novae Icones ... continentur / Autore Ioachimo Camerario, Reipub. Norimbrtg, Medico D.

This chapter explores the methods and materials of Vincent van Gogh’s Sunflowers, the painting now in the Van Gogh Museum, Amsterdam. Comprehensive physical and chemical investigations were performed using a range of non-invasive, in situ techniques combined with sample analysis. The results help to elucidate different stages of the artist’s working process, from making the canvas support, to the first charcoal sketch, the palette used, mixing and application of colour, paint texture and brushwork, as well as a wooden strip extension added late in the painting process. Comparisons are made with Van Gogh’s first painting of Sunflowers against a yellow background, now at the National Gallery in London

Conversation in the museum: experiments in dynamic hypermedia with the intelligent labelling explorer

We outline experience with the Intelligent Labelling Explorer, a dynamic hypertext system developed at the University of Edinburgh, in collaboration with the National Museums of Scotland. First, we indicate a number of ways in which labels on museum objects ought to be tuned to take into account types of visit, the interests of visitors, and their evolving knowledge during a visit. Secondly, we sketch the general architecture of our system, and then focus on the conversational effects which the system can create. We then briefly indicate future directions of research, before critically discussing the applicability (or otherwise) of the spatial metaphor to flexible hypertexts. Keywords: adaptive museum hypermedia, natural language techniques for dynamic hypertext generation, content adaptation in hypertext and hypermedia, web-based museum hypermedia, navigation design 1. Introduction We take dynamic hypertext to be that variety of flexible hypertext which relies upon techniques from th..