• Care Farming for People with Dementia; What Can Healthcare Leaders Learn from This Innovative Care Concept?

      De Bruin, Simone R; Pedersen, Ingeborg; Eriksen, Siren; Hassink, Jan; Vaandrager, Lenneke; Patil, Grete Grindal (2020-01-01)
    • The Care farming sector in the Netherlands: A reflection on its developments and promising innovations.

      Hassink, J; Agricola, H; Veen, EJ; Pijpker, R; de Bruin, SR; van der Meulen, HAB; Plug, LB (2020-06-22)
    • Carry-over of dioxins and PCBs from feed and soil to eggs at low contamination levels-- influence of mycotoxin binders on the carry-over from feed to eggs.

      Hoogenboom, L A P; Kan, C A; Zeilmaker, Marco J; Eijkeren, Jan C H van; Traag, Win A (2006-05-01)
      Laying hens were fed with compound feed containing six different levels of dioxins, dioxin-like PCBs and indicator PCBs for a period of 56 days. This was followed by a period of 56 days on clean feed. Dioxin levels in feed varied from background levels to three times the current EU tolerance limit of 0.75 ng TEQ/kg. At all dose levels a rapid increase was observed in the dioxin levels in eggs. There was a clear linear dose-response relationship between the dioxin levels in eggs and feed. The feed containing 0.4 ng TEQ dioxins per kg resulted in egg levels just above the EU limit of 3 pg TEQ/g fat. Dioxin-like and indicator PCB residues followed a pattern very similar to that of dioxins. Exposure to the highest indicator PCB level of 32 microg/kg resulted in egg levels around 300 ng/g fat. Exposure to dioxins through contaminated soil, mixed at 10% into the feed, resulted in a similar carry-over as from feed. Mycotoxin binders, mixed at 0.5% into the feed, had little effect on the carry-over of dioxins from the feed to the egg. It can be concluded that consumption of feed or soil with even moderate levels of dioxins and dioxin-like PCBs rapidly results in increased levels in eggs. The current EU dioxin limit for feed cannot guarantee egg dioxin levels below the EU-limit.
    • Cascading effects of predator activity on tick-borne disease risk.

      Hofmeester, Tim R; Jansen, Patrick A; Wijnen, Hendrikus J; Coipan, Elena C; Fonville, Manoj; Prins, Herbert H T; Sprong, Hein; van Wieren, Sipke E (2017-07-26)
      Predators and competitors of vertebrates can in theory reduce the density of infected nymphs (DIN)-an often-used measure of tick-borne disease risk-by lowering the density of reservoir-competent hosts and/or the tick burden on reservoir-competent hosts. We investigated this possible indirect effect of predators by comparing data from 20 forest plots across the Netherlands that varied in predator abundance. In each plot, we measured the density of questing Ixodes ricinus nymphs (DON), DIN for three pathogens, rodent density, the tick burden on rodents and the activity of mammalian predators. We analysed whether rodent density and tick burden on rodents were correlated with predator activity, and how rodent density and tick burden predicted DON and DIN for the three pathogens. We found that larval burden on two rodent species decreased with activity of two predator species, while DON and DIN for all three pathogens increased with larval burden on rodents, as predicted. Path analyses supported an indirect negative correlation of activity of both predator species with DON and DIN. Our results suggest that predators can indeed lower the number of ticks feeding on reservoir-competent hosts, which implies that changes in predator abundance may have cascading effects on tick-borne disease risk.
    • Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

      Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; et al. (2018-04)
      A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general practitioner participating in the routine sentinel surveillance of ILI in the Netherlands. The patient recovered fully. Further epidemiological and virological investigation did not reveal additional cases.
    • Case series of four secondary mucormycosis infections in COVID-19 patients, the Netherlands, December 2020 to May 2021.

      Buil, Jochem B; van Zanten, Arthur R H; Bentvelsen, Robbert G; Rijpstra, Tom A; Goorhuis, Bram; van der Voort, Sanne; Wammes, Linda J; Janson, Jeroen A; Melchers, Max; Heusinkveld, Moniek; et al.
    • Case study: Enschede fireworks disaster: lessons learned.

      van Kamp, I; van der Velden, P; Yzermans, J (2018-11-01)
    • A case-control study into risk factors for acute hepatitis E in the Netherlands, 2015-2017.

      Tulen, Anna Dolores; Vennema, Harry; van Pelt, Wilfrid; Franz, Eelco; Hofhuis, Agnetha (2019-02-08)
      A case-control study was performed (2015-2017) to identify risk factors for acute hepatitis E in the Netherlands. A questionnaire on potential sources of hepatitis E virus (HEV) exposure, health and socio-demographics was completed by 376 patients with acute hepatitis E, and 1534 controls matched for age, gender and region of residence. Traditional Dutch dry raw sausages of pork muscle meat, called "cervelaat", "snijworst", and "boerenmetworst" were reported by 72% of the patients, and 46% of controls (aOR 3.0; 95%CI 2.2-4.1), with a population attributable fraction (PAF) of 48%. Direct contact with pigs and working with a septic tank were strong risk factors (aOR 3.1; 95%CI 1.3-7.3 and aOR 6.9; 95%CI 1.2-40.8, respectively), with a low PAF (2% and 1%, respectively). Host risk factors were pre-existing liver disease (aOR 3.8; 95%CI 2.0-7.1), diabetes (aOR 2.1; 95%CI 1.4-3.2), immunosuppressive medication (aOR 2.5; 95%CI 1.5-4.1), and gastric acid inhibitors (aOR 2.3; 95%CI 1.7-3.1). Dry raw pork sausages were the major source of HEV infection among our study population. The prevalence and cause of HEV contamination in these pork muscle meat products require further investigation. Infrequently reported, yet strong risk factors were contact with pigs, or a septic tank.
    • A category approach for reproductive effects of phthalates.

      Fabjan, Evelin; Hulzebos, Etje; Mennes, W; Piersma, Aldert H (2006-10-01)
      In regulatory toxicology, the experimental assessment of reproductive toxicity is one of the most costly endpoints to perform. Categorizing chemicals is an approach that can be used to reduce animal tests in risk assessments of chemicals, for example, via REACH (Registration, Evaluation, and Authorization of Chemicals). The category approach was tested for reproductive toxicity with a group of 10 ortho-phthalate esters, with different side chain lengths. Three ortho-phthalates were used for testing the category. Phthalates with side-chain lengths C4 to C6 that are commonly known to cause reproductive effects were included, as well as the recently discovered mechanism that indicates antiandrogenic effects. The differences in physicochemical properties, absorption rates, and metabolism between the phthalates investigated could not fully explain the difference in reproductive toxicity. It was concluded that phthalates with the alkyl side-chain length from C4 to C6 produce similar severe reproductive effects in experimental animals. It is expected that phthalates included in the tight boundaries of the proposed category would all show severe reproductive effects, especially the antiandrogenic effects. Further testing might not be needed for phthalates within these boundaries. If necessary, limited testing could focus on the critical endpoints. Detailed mechanistic information is needed on phthalates to apply the categories for regulatory toxicology.
    • The cation competition and electrostatic theory are equally valid in quantifying the toxicity of trivalent rare earth ions (Y and Ce) to Triticum aestivum.

      Gong, Bing; He, Erkai; Qiu, Hao; Li, Jianqiu; Ji, Jie; Peijnenburg, Willie J G M; Liu, Yang; Zhao, Ling; Cao, Xinde (2019-07-01)
      There is a lack of appropriate models to delineate the toxicity of rare earth elements (REEs) while taking into account the factors that affect bioavailability. Here, standardized wheat (Triticum aestivum L.) root elongation tests were conducted to examine the impact of exposure conditions (i.e., varying Ca, Mg, Na, K and pH levels) on Y and Ce toxicity. Cation competition and electrostatic theory were examined for their applicability in explaining the observed variations in toxicity. Only Ca2+ and Mg2+ significantly alleviated the toxicity of Y3+ and Ce3+, while Na+, K+ and H+ showed no significant effects. Based on the cation competition, the derived binding constants for the hypothetical biotic ligands of wheat logKCaBL, logKMgBL, logKYBL, and logKCeBL were 3.87, 3.59, 6.70, and 6.48, respectively. The biotic ligand model (BLM) succeeded in predicting toxicities of Y and Ce, with more than 93% of the variance in toxicity explained. Given the BLM requires large data sets for deriving model parameters, attempts were further made to explore a simpler electrostatic based model to quantify REEs toxicity. The results demonstrated that the predictive capacity of the electrostatic approach, which considers ion activities at the plasma membrane surface, was comparable to that of BLM with at least 87% of the variations in toxicity explained. This suggested that the electrostatic theory can serve as a surrogate to BLM in modeling Y and Ce toxicities. Therefore, we recommend the BLM and electrostatic-based model as effective approaches to incorporate bioavailability in quantifying REEs toxicity in the presence of various levels of other major cations.
    • Cationically modified membranes using covalent layer-by-layer assembly for antiviral applications in drinking water.

      Sinclair TR; Patil A; Raza BG; Reurink D; Hengel SK van den; Rutjes SA; Roda Husman AM de; Roesink HDW; Vos WM de (2019-01-15)
    • CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells.

      Reinink, Peter; Souter, Michael N T; Cheng, Tan-Yun; van Gorkom, Tamara; Lenz, Stefanie; Kubler-Kielb, Joanna; Strle, Klemen; Kremer, Kristin; Thijsen, Steven F T; Steere, Allen C; et al. (2019-03-10)
      Lyme disease is a common multisystem disease caused by infection with a tick-transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL-II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL-II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b-BbGL-II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL-II-like molecules using tetramers and activation assays revealed a concomitant response to CD1b-expressing APCs in absence of BbGL-II. Further, among all major classes of self-lipid tested, BbGL-II responsive TCRs show strong cross-reactivity to diacylglycerol, a self-lipid antigen with structural similarities to BbGL-II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross-reactive CD1b-restricted T cell responses to bacterial and self-antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross-reactive T cells.
    • CDHR3 gene variation and childhood bronchiolitis.

      Husby, Anders; Pasanen, Anu; Waage, Johannes; Sevelsted, Astrid; Hodemaekers, Hennie; Janssen, Riny; Karjalainen, Minna K; Stokholm, Jakob; Chawes, Bo L; Korppi, Matti; et al. (2017-11)
    • Cell differentiation in the cardiac embryonic stem cell test (ESTc) is influenced by the oxygen tension in its underlying embryonic stem cell culture.

      Mennen, R H; de Leeuw, V C; Piersma, A H (2021-09-17)
      Oxygen (O2) levels in the mammalian embryo range between 2.4% and 8%. The cardiac embryonic stem cell test (ESTc) is a model for developmental toxicity predictions, which is usually performed under atmospheric O2 levels of 20%. We investigated the chemical sensitivity of the ESTc carried out under 20% O2, using embryonic stem cells (ESC) cultured under either 20% O2 or 5% O2. ESC viability was more sensitive to valproic acid (VPA) but less sensitive to flusilazole (FLU) when cultured under 5% versus 20% O2. For beating cardiomyocyte differentiation, lower ID50 values were found for FLU and VPA when the ESCs had been cultured under 5% versus 20% O2. At differentiation day 4, gene expression values were primarily driven by the level of O2 during ESC culture instead of exposure to FLU. In addition, using ESCs cultured under 5% O2 tension, VPA enhanced Nes (ectoderm) expression. Bmp4 (mesoderm) was enhanced by VPA when using ESCs cultured under 20% O2. At differentiation day 10, using ESCs cultured under 5% instead of 20% O2, Nkx2.5 and Myh6 (cardiomyocytes) were less affected after exposure to FLU or VPA. These results show that O2 tension in ESC culture influences chemical sensitivity in the ESTc. This enhances awareness of the standard culture conditions, which may impact the application of the ESTc in quantitative hazard assessment of chemicals.
    • The Challenge of Transparency and Validation in Health Economic Decision Modelling: A View from Mount Hood.

      Kent, Seamus; Becker, Frauke; Feenstra, Talitha; Tran-Duy, An; Schlackow, Iryna; Tew, Michelle; Zhang, Ping; Ye, Wen; Lizheng, Shi; Herman, William; et al. (2019-07-26)
    • Challenges in characterizing the environmental fate and effects of carbon nanotubes and inorganic nanomaterials in aquatic systems

      Laux, Peter; Riebeling, Christian; Booth, Andy M.; Brain, Joseph D.; Brunner, Josephine; Cerrillo, Cristina; Creutzenberg, Otto; Estrela-Lopis, Irina; Gebel, Thomas; Johanson, Gunnar; et al. (2018)
      Characterization of carbon nanotube dispersions requires measurement of both, concentration and surface area.
    • Challenges of implementing nano-specific safety and safe-by-design principles in academia

      Soeteman-Hernandez, LG; Blab, GA; Carattino, A; Dekker, F; Dekkers, S; van der Linden, M; van Silfhout, A; Noorlander, CW (2020-08-19)