• 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
    • 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.
    • A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

      Kirkland, David; Levy, Dan D; LeBaron, Matthew J; Aardema, Marilyn J; Beevers, Carol; Bhalli, Javed; Douglas, George R; Escobar, Patricia A; Farabaugh, Christopher S; Guerard, Melanie; Johnson, George E; Kulkarni, Rohan; Le Curieux, Frank; Long, Alexandra S; Lott, Jasmin; Lovell, David P; Luijten, Mirjam; Marchetti, Francesco; Nicolette, John J; Pfuhler, Stefan; Roberts, Daniel J; Stankowski, Leon F; Thybaud, Veronique; Weiner, Sandy K; Williams, Andrew; Witt, Kristine L; Young, Robert (2019-03-01)
      A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals.
    • The effect of chitosan on the bioaccessibility and intestinal permeability of acyclovir.

      Kubbinga, Marlies; Augustijns, Patrick; García, Mauricio A; Heinen, Christian; Wortelboer, Heleen M; Verwei, Miriam; Langguth, Peter (2019-03-01)
      Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir's bioaccessibility was studied using the dynamic TNO gastro-Intestinal Model (TIM-1). Four epithelial models were used for permeability experiments: a Caco-2 cell model in absence and presence of mucus and both rat and porcine excised intestinal segments. Study concentrations of acyclovir (0.8 g/l) and chitosan (1.6 g/l and 4 g/l) were in line with those used in the aforementioned human study. No effect of chitosan was measured on the bioaccessibility of acyclovir in the TIM-1 system. The results obtained with the Caco-2 models were not in line with the in vivo data. The tissue segment models (rat and porcine intestine) showed a negative trend of acyclovir's permeation in presence of chitosan. The Ussing type chamber showed to be the most biopredictive, as it did point to an overall statistically significantly reduced absorption of acyclovir. This model thus seems most appropriate for pharmaceutical development purposes, in particular when interactions between excipients and drugs are to become addressed.
    • Consumers' preferences for freezing of meat to prevent toxoplasmosis- A stated preference approach.

      Lambooij, Mattijs S; Veldwijk, Jorien; van Gils, Paul; Mangen, Marie-Josee J; Over, Eelco; Suijkerbuijk, Anita; Polder, Johan; de Wit, G Ardine; Opsteegh, Marieke (2019-03-01)
      Consumption of raw or undercooked meat increases the risk of infection with Toxoplasma gondii. Freezing meat products can eliminate this risk. Freezing of meat may affect consumers' valuation of meat products in two different ways: it may be valued positively because of increased food safety or valued negatively because of (perceived) loss of quality. In a Discrete Choice Experiment on four different meat products we studied the difference in willingness to pay for frozen and non-frozen meat products in the Netherlands. Analyses revealed that most Dutch consumer groups prefer non-frozen meat. Price was important in consumer decisions, whereas the meat being frozen appeared to play a minor role in the decision to purchase meat products. Even though it may seem obvious that people would prefer safe food to unsafe food, in a context where consumers presume food being safe, many consumers appear unwilling to pay for freezing of meat as additional measure to reduce the risk of food borne infections such as toxoplasmosis.
    • Selecting mixtures on the basis of dietary exposure and hazard data: application to pesticide exposure in the European population in relation to steatosis.

      Crépet, Amélie; Vanacker, Marie; Sprong, Corinne; de Boer, Waldo; Blaznik, Urska; Kennedy, Marc; Anagnostopoulos, Chris; Christodoulou, Despo Louca; Ruprich, Jiří; Rehurkova, Irena; Domingo, José Luis; Hamborg Jensen, Bodil; Metruccio, Francesca; Moretto, Angelo; Jacxsens, Liesbeth; Spanoghe, Pieter; Senaeve, David; van der Voet, Hilko; van Klaveren, Jacob (2019-03-01)
      Populations are exposed to mixtures of pesticides through their diet on a daily basis. The question of which substances should be assessed together remains a major challenge due to the complexity of the mixtures. In addition, the associated risk is difficult to characterise. The EuroMix project (European Test and Risk Assessment Strategies for Mixtures) has developed a strategy for mixture risk assessment. In particular, it has proposed a methodology that combines exposures and hazard information to identify relevant mixtures of chemicals belonging to any cumulative assessment group (CAG) to which the European population is exposed via food. For the purposes of this study, food consumption and pesticide residue data in food and drinking water were obtained from national surveys in nine European countries. Mixtures of pesticides were identified by a sparse non-negative matrix underestimation (SNMU) applied to the specific liver steatosis effect in children from 11 to 15 years of age, and in adults from 18 to 64 years of age in nine European countries. Exposures and mixtures of 144 pesticides were evaluated through four different scenarios: (1) chronic exposure with a merged concentration dataset in the adult population, (2) chronic exposure with country-specific concentration datasets in the adult population, (3) acute exposure with a merged concentration dataset in the adult population, and (4) chronic exposure with a merged concentration dataset in the paediatric population. The relative potency factors of each substance were calculated to express their potency relative to flusilazole, which was chosen as the reference compound. The selection of mixtures and the evaluation of exposures for each country were carried out using the Monte Carlo Risk Assessment (MCRA) software. Concerning chronic exposure, one mixture explained the largest proportion of the total variance for each country, while in acute exposure, several mixtures were often involved. The results showed that there were 15 main pesticides in the mixtures, with a high contribution of imazalil and dithiocarbamate. Since the concentrations provided by the different countries were merged in the scenario using merged concentration data, differences between countries result from differences in food consumption behaviours. These results support the approach that using merged concentration data to estimate exposures in Europe seems to be realistic, as foods are traded across European borders. The originality of the proposed approach was to start from a CAG and to integrate information from combined exposures to identify a refined list of mixtures with fewer components. As this approach was sensitive to the input data and required significant resources, efforts should continue regarding data collection and harmonisation among the different aspects within the pesticides regulatory framework, and to develop methods to group substances and mixtures to characterise the risk.
    • Op de loer in de modder en oppervlaktewater: Leptospira en Francisella tularensis

      Pijnacker R; Joosten R; Janse I; Brandwagt D; Fanoy E; Dam S van; Petrignani M; Weijden C van der; Schets F; Giessen J van der; Rijckevorsel G van; Tulen A; Pelt J van; Winkeler L; Kraaijeveld A; Goris M; Franz E (2019-03)
    • Obstacle runs en infectieziekten: tips voor de GGD-praktijk

      Oorsprong DM; Boogert EM den; Buiting MP; Hondema LS; Ewalts H; Dam ASG van (2019-03)
    • Predictable and unpredictable survival of foodborne pathogens during non-isothermal heating.

      de Jonge, R (2019-02-16)
      In previous work, extreme survival of various bacterial species during cooking was reported when attached to chicken meat. In this paper the effects of an extremely high challenge temperature on survival of Salmonella Typhimurium and Campylobacter jejuni, attached to chicken breast fillets or pork to test for matrix effects are reported. Survival was predicted, using standard D- and z-values from the literature, and compared to experimentally obtained data. Attached to meat, both S. Typhimurium and C. jejuni survived longer than predicted, longer when attached to chicken meat than when attached to pork. Additionally, the effect of non-isothermal heating on survival of almonella in buffer is described. In buffer, when slowly heated, Salmonella died off as predicted. When Salmonella was heated in buffer according to a heating profile mimicking that of the surface of meat in boiling water, it appeared that cells died off much slower than predicted. It is shown that the thermal characteristics of Salmonella surviving the first 35 s of fast heating had changed. After these 35 s, remaining Salmonella survived for minutes, even at a challenge temperature of 90 °C. During heating, cell size decline was observed. A loss of intracellular water during cooking might have resulted in smaller, dehydrated cells, in cells with altered thermal resistance characteristics. This could explain why the use of standard D-and z-values did not allow the correct prediction of survival of Salmonella during fast heating in buffer, or during cooking, being attached to the surface of meat. Many factors affect the level of heat resistance of bacteria. The results of this and a former study show that attachment to meat contributes to an increased level of heat resistance of bacteria. A fast heating process further contributes to the increased level of heat resistance possibly as the result of changed thermal characteristics due to a loss of water.
    • Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

      Pennells, Lisa; Kaptoge, Stephen; Wood, Angela; Sweeting, Mike; Zhao, Xiaohui; White, Ian; Burgess, Stephen; Willeit, Peter; Bolton, Thomas; Moons, Karel G M; van der Schouw, Yvonne T; Selmer, Randi; Khaw, Kay-Tee; Gudnason, Vilmundur; Assmann, Gerd; Amouyel, Philippe; Salomaa, Veikko; Kivimaki, Mika; Nordestgaard, Børge G; Blaha, Michael J; Kuller, Lewis H; Brenner, Hermann; Gillum, Richard F; Meisinger, Christa; Ford, Ian; Knuiman, Matthew W; Rosengren, Annika; Lawlor, Debbie A; Völzke, Henry; Cooper, Cyrus; Marín Ibañez, Alejandro; Casiglia, Edoardo; Kauhanen, Jussi; Cooper, Jackie A; Rodriguez, Beatriz; Sundström, Johan; Barrett-Connor, Elizabeth; Dankner, Rachel; Nietert, Paul J; Davidson, Karina W; Wallace, Robert B; Blazer, Dan G; Björkelund, Cecilia; Donfrancesco, Chiara; Krumholz, Harlan M; Nissinen, Aulikki; Davis, Barry R; Coady, Sean; Whincup, Peter H; Jørgensen, Torben; Ducimetiere, Pierre; Trevisan, Maurizio; Engström, Gunnar; Crespo, Carlos J; Meade, Tom W; Visser, Marjolein; Kromhout, Daan; Kiechl, Stefan; Daimon, Makoto; Price, Jackie F; Gómez de la Cámara, Agustin; Wouter Jukema, J; Lamarche, Benoît; Onat, Altan; Simons, Leon A; Kavousi, Maryam; Ben-Shlomo, Yoav; Gallacher, John; Dekker, Jacqueline M; Arima, Hisatomi; Shara, Nawar; Tipping, Robert W; Roussel, Ronan; Brunner, Eric J; Koenig, Wolfgang; Sakurai, Masaru; Pavlovic, Jelena; Gansevoort, Ron T; Nagel, Dorothea; Goldbourt, Uri; Barr, Elizabeth L M; Palmieri, Luigi; Njølstad, Inger; Sato, Shinichi; Monique Verschuren, W M; Varghese, Cherian V; Graham, Ian; Onuma, Oyere; Greenland, Philip; Woodward, Mark; Ezzati, Majid; Psaty, Bruce M; Sattar, Naveed; Jackson, Rod; Ridker, Paul M; Cook, Nancy R; D'Agostino, Ralph B; Thompson, Simon G; Danesh, John; Di Angelantonio, Emanuele (2019-02-14)
      There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
    • Impact of NBS for VLCAD deficiency on genetic, enzymatic and clinical outcomes.

      Bleeker, Jeannette C; Kok, Irene L; Ferdinandusse, Sacha; van der Pol, W Ludo; Cuppen, Inge; Bosch, Annet M; Langeveld, Mirjam; Derks, Terry G J; Williams, Monique; de Vries, Maaike; Mulder, Margot F; Rubio Gozalbo, Estela; van der Velden, Monique G M de Sain-; Rennings, Alexander J; Schielen, Peter J C I; Dekkers, Eugenie; Houtkooper, Riekelt H; Waterham, Hans R; Pras-Raves, Mia L; Wanders, Ronald J A; van Hasselt, Peter M; Schoenmakers, Marja; Wijburg, Frits A; Visser, Gepke (2019-02-13)
      Most infants with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. If this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms, is unclear. A 10 year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS. Main outcome measures were clinical outcome parameters, ACADVL gene analysis, VLCAD activity and overall capacity of long-chain fatty acid oxidation (LC-FAO flux) in lymphocytes and cultured skin fibroblasts. Median VLCAD activity in lymphocytes of 54 patients, 21 diagnosed pre-NBS and 33 by NBS was respectively 5.4% (95% CI 4.0-8.3%) and 12.6% (95% CI 10.7-17.7%; p<.001) of the reference mean. The median LC-FAO flux was 33.2% (95% CI 22.8-48.3%) and 41% (95% CI 40.8-68%; p<.05) of the control mean, respectively. Clinical characteristics in 23 pre-NBS and 37 NBS patients revealed hypoglycemic events in 12 versus 2 patients, cardiomyopathy in 5 versus 4 patients and myopathy in 14 versus 3 patients. All patients with LC-FAO flux <10% developed symptoms. Of the patients with LC-FAO flux >10% 7 out of 12 diagnosed pre-NBS versus none by NBS experienced hypoglycemic events. NBS has a clear beneficial effect on the prevention of hypoglycemic events in patients with some residual enzyme activity, but does not prevent hypoglycemia nor cardiac complications in patients with very low residual enzyme activity. The effect of NBS on prevalence and prevention of myopathy-related complications remains unclear.
    • A quantitative risk assessment for human Taenia solium exposure from home slaughtered pigs in European countries.

      Meester, Marina; Swart, Arno; Deng, Huifang; van Roon, Annika; Trevisan, Chiara; Dorny, Pierre; Gabriël, Sarah; Vieira-Pinto, Madalena; Johansen, Maria Vang; van der Giessen, Joke (2019-02-12)
      Taenia solium, a zoonotic tapeworm, is responsible for about a third of all preventable epilepsy human cases in endemic regions. In Europe, adequate biosecurity of pig housing and meat inspection practices have decreased the incidence of T. solium taeniosis and cysticercosis. Pigs slaughtered at home may have been raised in suboptimal biosecurity conditions and slaughtered without meat inspection. As a result, consumption of undercooked pork from home slaughtered pigs could pose a risk for exposure to T. solium. The aim of this study was to quantify the risk of human T. solium exposure from meat of home slaughtered pigs, in comparison to controlled slaughtered pigs, in European countries. A quantitative microbial risk assessment model (QMRA) was developed and porcine cysticercosis prevalence data, the percentage of home slaughtered pigs, meat inspection sensitivity, the cyst distribution in pork and pork consumption in five European countries, Bulgaria, Germany, Poland, Romania and Spain, were included as variables in the model. This was combined with literature about cooking habits to estimate the number of infected pork portions eaten per year in a country. The results of the model showed a 13.83 times higher prevalence of contaminated pork portions from home slaughtered pigs than controlled slaughtered pigs. This difference is brought about by the higher prevalence of cysticercosis in pigs that are home raised and slaughtered. Meat inspection did not affect the higher exposure from pork that is home slaughtered. Cooking meat effectively lowered the risk of exposure to T. solium-infected pork. This QMRA showed that there is still a risk of obtaining an infection with T. solium due to consumption of pork, especially when pigs are reared and slaughtered at home, using data of five European countries that reported porcine cysticercosis cases. We propose systematic reporting of cysticercosis cases in slaughterhouses, and in addition molecularly confirming suspected cases to gain more insight into the presence of T. solium in pigs and the risk for humans in Europe. When more data become available, this QMRA model could be used to evaluate human exposure to T. solium in Europe and beyond.
    • The public uptake of information about antibiotic resistance in the Netherlands.

      van Rijn, Michiel; Haverkate, Manon; Achterberg, Peter; Timen, Aura (2019-02-12)
      In this study, we test to what extent an educational video on the intricacies of antibiotic resistance affects public attitudes towards antibiotic resistance and how such information is absorbed by the most likely targets of public health campaigns. We use a representative sample of 2037 individuals (from 2016) to test how people respond to a video educating them about antibiotic resistance. Our results show that receiving information does increase the general awareness of antibiotic resistance among our respondents. Yet, these effects are most profound for those who are the most likely targets of such information: the least knowledgeable group and those who have a more apathetic worldview. Our results are in line with suggestions made by the knowledge deficit model and show that the influence of cultural predispositions on the uptake of information about antibiotic resistance should not be ignored in future campaigns.
    • Effect of diet with or without exercise on abdominal fat in postmenopausal women - a randomised trial.

      van Gemert, Willemijn A; Peeters, Petra H; May, Anne M; Doornbos, Adriaan J H; Elias, Sjoerd G; van der Palen, Job; Veldhuis, Wouter; Stapper, Maaike; Schuit, Jantine A; Monninkhof, Evelyn M (2019-02-11)
      We assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study. The SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012-2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6-7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method. The diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (- 12.5% and - 12.0%) and exercise plus diet (- 16.0% and - 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm We conclude that weight loss of 6-7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction.
    • Does breast milk adiponectin affect BMI and cardio-metabolic markers in childhood?

      van Rossem, Lenie; Smit, Henriette A; Lentjes, Eef Gwm; Maitimu-Smeele, Inge; Brunekreef, Bert; Koppelman, Gerard H; Wijga, Alet H (2019-02-07)
    • Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study.

      Vissers, Linda E T; Sluijs, Ivonne; van der Schouw, Yvonne T; Forouhi, Nita G; Imamura, Fumiaki; Burgess, Stephen; Barricarte, Aurelio; Boeing, Heiner; Bonet, Catalina; Chirlaque, Maria-Dolores; Fagherazzi, Guy; Franks, Paul W; Freisling, Heinz; Gunter, Marc J; Quirós, J Ramón; Ibsen, Daniel B; Kaaks, Rudolf; Key, Timothy; Khaw, Kay T; Kühn, Tilman; Mokoroa, Olatz; Nilsson, Peter M; Overvad, Kim; Pala, Valeria; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Spijkerman, Annemieke M W; Tjonneland, Anne; Tumino, Rosario; Rodríguez-Barranco, Miguel; Rolandsson, Olov; Riboli, Elio; Sharp, Stephen J; Langenberg, Claudia; Wareham, Nicholas J (2019-02-06)
      To estimate the causal association between intake of dairy products and incident type 2 diabetes. The analysis included 21,820 European individuals (9,686 diabetes cases) of the EPIC-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a SNP for lactase persistence (LP) which enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratio 0.99 rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations we consider it unlikely that this has caused the observed null result.
    • Physical activity levels of women with breast cancer during and after treatment, a comparison with the Dutch female population.

      Gal, R; Monninkhof, E M; Peeters, P H M; van Gils, C H; van den Bongard, D H J G; Wendel-Vos, G C W; Zuithoff, N P A; Verkooijen, H M; May, A M (2019-02-06)
      Physical activity has been shown to reduce side-effects of breast cancer and its treatment. As physical activity levels of patients with breast cancer are largely unknown, we investigated these levels and compared them to women from the general population. In this prospective cohort study, physical activity levels of women with breast cancer participating in the UMBRELLA cohort were assessed at radiotherapy intake and thereafter every 6 months up to 3 years with the SQUASH questionnaire, which was also used in a random sample of the Dutch population. We compared physical activity levels (no activity, low, moderate or high levels of sports, leisure time or total activity) between patients and the Dutch female population using multinomial logistic regression. Standardized Prevalence Ratios (SPR) were calculated to compare adherence to Dutch physical activity guidelines. Women with breast cancer (n Physical activity levels in women with breast cancer during and after treatment were lower compared to the Dutch female population. Three years post-treatment, they were still less physically active, although they spend more time in sport activities. As about half of the patients did not perform any sports, physical activity needs to be stimulated during and after treatment.