Recent Submissions

  • Toward optimisation of water use efficiency in dryland pastures using carbon isotope discrimination as a tool to select plant species mixtures.

    Pronger, J; Campbell, D I; Clearwater, M J; Mudge, P L; Rutledge, S; Wall, A M; Schipper, L A (2019-05-15)
    Pastoral agriculture is important for supplying global demand for animal products but pasture productivity is often water limited. Increased plant diversity has been shown to increase water use efficiency (ω) and productivity under water limitation but the optimal mix of species varies spatially, dependent on climate, soil type, and plant water requirements. Consequently, a cost-effective method to screen for high ω plant species and mixes in situ at farm scale is needed. Using carbon isotope discrimination (∆
  • Monitoring of pork liver and meat products on the Dutch market for the presence of HEV RNA.

    Boxman, Ingeborg L A; Jansen, Claudia C C; Hägele, Geke; Zwartkruis-Nahuis, Ans; Tijsma, Aloys S L; Vennema, Harry (2019-05-02)
    The aim of the present study was to assess pork liver and meat products present on the Dutch market for the presence of hepatitis E virus (HEV) RNA. HEV RNA was detected in 27.3% of 521 products sampled from Dutch retail stores in 2016. 12.7% of livers were positive for HEV RNA (n = 79), 70.7% of liverwurst (n = 99), 68.9% of liver pate (n = 90), but in none of the pork chops (n = 98), fresh sausages (n = 103) or wild boar meat (n = 52). The highest level of HEV RNA contamination was observed in a liver (reaching up to 1 × 10
  • Analytical approaches for characterizing and quantifying engineered nanoparticles in biological matrices from an (eco)toxicological perspective: old challenges, new methods and techniques.

    Abdolahpur Monikh, Fazel; Chupani, Latifeh; Vijver, Martina G; Vancová, Marie; Peijnenburg, Willie J G M (2019-04-10)
    To promote the safer by design strategy and assess environmental risks of engineered nanoparticles (ENPs), it is essential to understand the fate of ENPs within organisms. This understanding in living organisms is limited by challenges in characterizing and quantifying ENPs in biological media. Relevant literature in this area is scattered across research from the past decade or so, and it consists mostly of medically oriented studies. This review first introduces those modern techniques and methods that can be used to extract, characterize, and quantify ENPs in biological matrices for (eco)toxicological purposes. It then summarizes recent research developments within those areas most relevant to the context and field that are the subject of this review paper. These comprise numerous in-situ techniques and some ex-situ techniques. The former group includes techniques allowing to observe specimens in their natural hydrated state (e.g., scanning electron microscopy working in cryo mode and high-pressure freezing) and microscopy equipped with elemental microanalysis (e.g., energy-dispersive X-ray spectroscopy); two-photon laser and coherent anti-Stokes Raman scattering microscopy; absorption-edge synchrotron X-ray computed microtomography; and laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS). The latter group includes asymmetric flow field flow fractionation coupled with ICP-MS and single particle-ICP-MS. Our review found that most of the evidence gathered for ENPs actually focused on a few metal-based ENPs and carbon nanotube and points to total mass concentration but no other particles properties, such as size and number. Based on the obtained knowledge, we developed and presented a decision scheme and analytical toolbox to help orient scientists toward selecting appropriate ways for investigating the (eco)toxicity of ENPs that are consistent with their properties.
  • Predictors of stunting with particular focus on complementary feeding practices: A cross-sectional study in the northern province of Rwanda.

    Uwiringiyimana, Vestine; Ocké, Marga C; Amer, Sherif; Veldkamp, Antonie (2019-04-01)
    The aim of this study was to review the factors associated with stunting in the northern province of Rwanda by assessing anthropometric status, dietary intake, and overall complementary feeding practices. This was a cross-sectional study with 138 children 5 to 30 mo of age. A structured questionnaire was used to collect information on sociodemographic characteristics of each mother and child and breastfeeding and complementary feeding practices. Anthropometric status was assessed using height-for-age z-scores for children and body mass index for caregivers. Dietary intakes were estimated using a 24-h recall. Multiple linear and logistic regression models were performed to study the predictors of height-for-age z scores and stunting. There was a 42% stunting prevalence. Prevalence of continued breastfeeding and exclusive breastfeeding were 92% and 50%, respectively. Most children (62%) fell into the low dietary diversity score group. The nutrient intake from complementary foods was below recommendations. The odds of stunting were higher in children >12 mo of age (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.08-1.29). Exclusive breastfeeding (OR, 0.22; 95% CI, 0.10-0.48) and deworming tablet use in the previous 6 mo (OR, 0.25; 95% CI, 0.07-0.80) decreased significantly the odds of stunting in children. Also, the body mass index of the caretaker (β = 0.08 kg/m Interventions focusing on optimal nutrition during the complementary feeding stage, exclusive breastfeeding, and the use of deworming tablets have the potential to substantially reduce stunting in children in the northern province of Rwanda.
  • Test sensitivity of a commercial serine protease digestion kit for the detection of Trichinella spiralis and Trichinella pseudospiralis larvae in pig muscle.

    Franssen, F; Johne, A; van der Giessen, J; Nöckler, K; Mayer-Scholl, A (2019-04-01)
    The reference method for Trichinella detection at meat inspection is the magnetic stirrer method (MSM) utilising HCl-pepsin for pooled sample digestion. Due to availability and quality issues with pepsin, alternative digestion methods are being offered, such as the Priocheck Trichinella AAD kit (T-AAD), based on serine endopeptidase digestion. In this study the T-AAD kit was compared to the reference method. Minced pork samples were spiked with T. spiralis muscle larvae (ML) with- and without capsule or T. pseudospiralis ML, and analysed with both tests. Test results of individually spiked test samples were analysed by generalised linear modelling. The T-AAD test kit was comparable to the reference method for the qualitative detection of T. spiralis in pigs, but not quantitatively. Overall, 94% of spiked T. spiralis were recovered using MSM against 75.2% when using T-AAD (p < 0.0001). Using the MSM 80.0% of spiked T. pseudospiralis were recovered against 20% with the T-AAD (p < 0.0001). Based on our experience with the T-AAD kit, we strongly recommend validating the method on site prior to introduction into routine diagnostic laboratories, but this will not alleviate the poor test sensitivity of the T-AAD for the detection of T. pseudospiralis.
  • A DFT/TDDFT study on the mechanisms of direct and indirect photodegradation of tetrabromobisphenol A in water.

    Wang, Se; Wang, Zhuang; Hao, Ce; Peijnenburg, Willie J G M (2019-04-01)
    Tetrabromobisphenol A (TBBPA) is the most widely used commercial brominated flame retardant. However, the mechanisms underlying the photodegradation of TBBPA remain unclear. Here we use density functional theory and time-dependent density functional theory to examine the photodegradation of the two species of TBBPA in water: TBBPA (neutral form) and TBBPA
  • Health Policy Performance in 16 Caribbean States, 2010-2015.

    Verstraeten, Soraya P A; van Oers, Hans A M; Mackenbach, Johan P (2019-04-01)
    To determine whether Caribbean states vary in health policy performance in 11 different areas; to explore the association with sociodemographic, economical, and governance determinants; and to estimate the potential health gains of "best-practice" health policies. We selected 50 indicators that included data on mortality (latest available, 2010-2015), intermediate outcomes, and policy implementation to calculate a state's health policy performance score. We related this score to country characteristics and calculated the potential number of avoidable deaths if the age-specific mortality rates of best-performer Martinique applied in all states. We found large differences in health policy performance among Caribbean states. Martinique, Cuba, and Guadeloupe had the highest performance scores, and Guyana, Belize, and Suriname the lowest. Political affiliation, religious fractionalization, corruption, national income, and population density were associated with health policy performance. If the mortality rates of Martinique applied to all Caribbean states, an overall mortality reduction of 12% would be achieved. Differences in health outcomes between Caribbean states are partly attributable to variations in health policy implementation. Our results suggest that many deaths can be prevented if Caribbean governments adopt best-practice policies.
  • Optimizing molecular surveillance of mumps genotype G viruses.

    Bodewes, Rogier; van Rooijen, Kristel; Cremer, Jeroen; Veldhuijzen, Irene K; van Binnendijk, Rob (2019-04-01)
    Mumps viruses continue to cause sporadic cases and outbreaks in countries with a high vaccination coverage for mumps. Molecular surveillance of mumps viruses can be supportive to elucidate the origin and transmission routes of mumps virus in case of an outbreak. Currently, molecular surveillance is worldwide primarily focused on sequencing of the small hydrophobic (SH) gene. However, few studies have already shown that additional genes or regions contribute to the resolution of the sequence data in such a way that mumps cases that seem to be linked to the same source on basis of the SH sequence, appear to be linked to another source or chain of transmission. Notably, this sequence information was recently extracted from the hemagglutinin-neuraminidase (HN) and fusion (F) genes (total 3364 nucleotides), or from the sum of the three non-coding regions (NCRs; total 1954 nt) between the nucleocapsid protein, phosphoprotein, matrix protein and F protein, but also from the complete genome. Here, sequence data from NCRs were compared with that of the HN and F gene, using mumps genotype G viruses detected in the Netherlands between 2010 and 2018. Results of this study indicate that NCRs sequence data provided similar or slightly better sequence resolution compared to the HN and F genes for most viruses. For molecular surveillance of currently circulating mumps genotype G viruses is sequencing of SH in combination with NCRs currently a useful approach.
  • Newborn screening for sickle cell disease in Europe.

    Daniel, Y; Elion, J; Allaf, B; Badens, C; Bouva, MJ; Brincat, I; Cela, E; Coppinger, C (2019-03-19)
  • Analysis of manufacturer's information on tobacco product additive use.

    van Nierop, LE; Pennings, JLA; Schenk, E; Kienhuis, AS; Talhout, R (2019-03-19)
  • Look-alikes may not act alike: Gene expression regulation and cell-type-specific responses of three valproic acid analogues in the neural embryonic stem cell test (ESTn).

    de Leeuw, Victoria C; Hessel, Ellen V S; Piersma, Aldert H (2019-03-15)
    In vitro assays to assess developmental neurotoxicity of chemicals are highly desirable. The murine neural embryonic stem cell test (ESTn) can mimic parts of early differentiation of embryonic brain and may therefore be useful for this purpose. The aim of this study was to investigate whether this test is able to rank the toxic potencies of three valproic acid analogues and to study their mode of action by investigating their individual effects on four cell types: stem cells, neurons, astrocytes and neural crest cells. Using immunocytochemical read-outs and qPCR for cell type-specific genes, the effects of valproic acid (VPA), 2-ethylhexanoic acid (EHA) and 2-ethyl-4-methylpentanoic (EMPA) were assessed. VPA and EHA but not EMPA downregulated cell type-specific differentiation makers and upregulated stem cell related markers (Fut4, Cdh1) at different time points during differentiation. Expression of Gfap, a marker for astrocytes, was dramatically downregulated by VPA and EHA, but not by EMPA. This finding was verified using immunostainings. Based on the number and extent of genes regulated by the three compounds, relative potencies were determined as VPA > EHA > EMPA, which is consistent with in vivo developmental toxicity potency ranking of these compounds. Thus, ESTn using a combination of morphology, gene and protein expression readouts, may provide a medium-throughput system for monitoring the effects of compounds on differentiation of cell types in early brain development.
  • Substitutions between dairy products and risk of stroke: Results from the EPIC-NL cohort.

    Laursen, Anne Sofie D; Sluijs, Ivonne; Boer, Jolanda M A; Verschuren, W M Monique; van der Schouw, Yvonne T; Jakobsen, Marianne U (2019-03-14)
    The association between intake of different dairy products and the risk of stroke remains unclear. We therefore investigated substitutions between dairy product subgroups and risk of stroke. We included 36,886 Dutch men and women. Information about dairy product intake was collected through a food frequency questionnaire. Dairy products were grouped as low-fat milk, whole-fat milk, buttermilk, low-fat yoghurt, whole-fat yoghurt, cheese and butter. Incident stroke cases were identified in national registers. We used Cox proportional hazards regression to calculate associations for substitutions between dairy products with the rate of stroke. During a median follow-up of 15.2 years we identified 884 stroke cases (503 ischemic and 244 hemorrhagic). Median intake of total dairy products was 4 servings/day. Low-fat yoghurt substituted for whole fat yoghurt was associated with a higher rate of ischemic stroke (HR = 2.58, 95 % CI: 1.11, 5.97 per serving/day). Whole fat yoghurt as a substitution for any other subgroup was associated with a lower rate of ischemic stroke (HRs between 0.33 and 0.36 per serving/day). We did not observe any associations for hemorrhagic stroke. In conclusion, whole-fat yoghurt as a substitution for low-fat yoghurt, cheese, butter, buttermilk or milk regardless of fat content was associated with a lower rate of ischemic stroke.
  • Health Risks of Polybrominated Diphenyl Ethers (PBDEs) and Metals at Informal Electronic Waste Recycling Sites.

    Ohajinwa, Chimere May; van Bodegom, Peter M; Osibanjo, Oladele; Xie, Qing; Chen, Jingwen; Vijver, Martina G; Peijnenburg, Willie J G M (2019-03-13)
    Concerns about the adverse public health consequences of informal electronic waste (
  • Cytosolic glucosylceramide regulates endolysosomal function in Niemann-Pick type C disease.

    Wheeler, Simon; Haberkant, Per; Bhardwaj, Meenakshi; Tongue, Paige; Ferraz, Maria J; Halter, David; Sprong, Hein; Schmid, Ralf; Aerts, Johannes M F G; Sullo, Nikol; Sillence, Dan J (2019-03-12)
    Niemann-Pick type C disease (NPCD) is a neurodegenerative disease associated with increases in cellular cholesterol and glycolipids and most commonly caused by defective NPC1, a late endosomal protein. Using ratiometric probes we find that NPCD cells show increased endolysosomal pH. In addition U18666A, an inhibitor of NPC1, was found to increase endolysosomal pH, and the number, size and heterogeneity of endolysosomal vesicles. NPCD fibroblasts and cells treated with U18666A also show disrupted targeting of fluorescent lipid BODIPY-LacCer to high pH vesicles. Inhibiting non-lysosomal glucocerebrosidase (GBA2) reversed increases in endolysosomal pH and restored disrupted BODIPY-LacCer trafficking in NPCD fibroblasts. GBA2 KO cells also show decreased endolysosomal pH. NPCD fibroblasts also show increased expression of a key subunit of the lysosomal proton pump vATPase on GBA2 inhibition. The results are consistent with a model where both endolysosomal pH and Golgi targeting of BODIPY-LacCer are dependent on adequate levels of cytosolic-facing GlcCer, which are reduced in NPC disease.
  • Viral Infection of Human Natural Killer Cells.

    van Erp, Elisabeth A; van Kampen, Mirjam R; van Kasteren, Puck B; de Wit, Jelle (2019-03-12)
    Natural killer (NK) cells are essential in the early immune response against viral infections, in particular through clearance of virus-infected cells. In return, viruses have evolved multiple mechanisms to evade NK cell-mediated viral clearance. Several unrelated viruses, including influenza virus, respiratory syncytial virus, and human immunodeficiency virus, can directly interfere with NK cell functioning through infection of these cells. Viral infection can lead to immune suppression, either by downregulation of the cytotoxic function or by triggering apoptosis, leading to depletion of NK cells. In contrast, some viruses induce proliferation or changes in the morphology of NK cells. In this review article, we provide a comprehensive overview of the viruses that have been reported to infect NK cells, we discuss their mechanisms of entry, and describe the interference with NK cell effector function and phenotype. Finally, we discuss the contribution of virus-infected NK cells to viral load. The development of specific therapeutics, such as viral entry inhibitors, could benefit from an enhanced understanding of viral infection of NK cells, opening up possibilities for the prevention of NK cell infection.
  • Raising awareness of false positive newborn screening results arising from pivalate-containing creams and antibiotics in Europe when screening for isovaleric acidaemia.

    Bonham, JR; Carling, RS; Lindner, M; Franszon, L; Zetterstrom, R; Boemer, F; Cerone, R; Eyskens, F; Vilarinho, L; Hougaard, M; Schielen, PJCI (2019-03-12)
  • Introducing newborn screening for severe combined immunodeficiency (SCID) in the Dutch Neonatal Screening Program.

    Blom, M; Bredius, RGM; Weijman, G; Dekkers, EHBM; Kemper, EA; van den Akker-van Marle, ME; van der Ploeg, CPB; van der Burg, M; Schielen, PCJI (2019-03-12)
  • Targeting the thioredoxin system as a novel strategy against B cell acute lymphoblastic leukemia.

    Fidyt, Klaudyna; Pastorczak, Agata; Goral, Agnieszka; Szczygiel, Kacper; Fendler, Wojciech; Muchowicz, Angelika; Bartlomiejczyk, Marcin Adam; Madzio, Joanna; Cyran, Julia; Graczyk-Jarzynka, Agnieszka; Jansen, Eugene; Patkowska, Elzbieta; Lech-Maranda, Ewa; Pal, Deepali; Blair, Helen; Burdzinska, Anna; Pedzisz, Piotr; Glodkowska-Mrowka, Eliza; Demkow, Urszula; Gawle-Krawczyk, Karolina; Matysiak, Michal; Winiarska, Magdalena; Juszczynski, Przemyslaw; Mlynarski, Wojciech; Heidenreich, Olaf; Golab, Jakub; Firczuk, Malgorzata (2019-03-12)
    B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogeneous blood cancer characterized by abnormal expansion of immature B cells. Although intensive chemotherapy provides high cure rates in a majority of patients, subtypes harboring certain genetic lesions, such as MLL rearrangements or BCR-ABL1 fusion, remain clinically challenging, necessitating a search for other therapeutic approaches. Herein, we aimed to validate antioxidant enzymes of the thioredoxin system as potential therapeutic targets in BCP-ALL. We observed oxidative stress along with aberrant expression of the enzymes associated with the activity of thioredoxin antioxidant system in BCP-ALL cells. Moreover, we found that auranofin and adenanthin, inhibitors of the thioredoxin system antioxidant enzymes, effectively kill BCP-ALL cell lines and pediatric and adult BCP-ALL primary cells, including primary cells co-cultured with bone marrow-derived stem cells. Furthermore, auranofin delayed the progression of leukemia in MLL-rearranged patient-derived xenograft model and prolonged the survival of leukemic NSG mice. Our results unveil the thioredoxin system as a novel target for BCP-ALL therapy, and indicate that further studies assessing the anticancer efficacy of combinations of thioredoxin system inhibitors with conventional anti BCP-ALL drugs should be continued.
  • High resolution annual average air pollution concentration maps for the Netherlands.

    Schmitz, Oliver; Beelen, Rob; Strak, Maciej; Hoek, Gerard; Soenario, Ivan; Brunekreef, Bert; Vaartjes, Ilonca; Dijst, Martin J; Grobbee, Diederick E; Karssenberg, Derek (2019-03-12)
    Long-term exposure to air pollution is considered a major public health concern and has been related to overall mortality and various diseases such as respiratory and cardiovascular disease. Due to the spatial variability of air pollution concentrations, assessment of individual exposure to air pollution requires spatial datasets at high resolution. Combining detailed air pollution maps with personal mobility and activity patterns allows for an improved exposure assessment. We present high-resolution datasets for the Netherlands providing average ambient air pollution concentration values for the year 2009 for NO

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