• Beijing/W genotype Mycobacterium tuberculosis and drug resistance.

      Glynn, Judith R; Kremer, Kristin; Borgdorff, Martien W; Rodriguez, Mar Pujades; Soolingen, Dick van (2006-05-01)
      Beijing/W genotype Mycobacterium tuberculosis is widespread, may be increasing, and may have a predilection for drug resistance. Individual-level data on >29,000 patients from 49 studies in 35 countries were combined to assess the Beijing genotype's prevalence worldwide, trends over time and with age, and associations with drug resistance. We found 4 patterns for Beijing/W genotype tuberculosis (TB): 1) endemic, not associated with drug resistance (high level in most of East Asia, lower level in parts of the United States); 2) epidemic, associated with drug resistance (high level in Cuba, the former Soviet Union, Vietnam, and South Africa, lower level in parts of Western Europe); 3) epidemic but drug sensitive (Malawi, Argentina); and 4) very low level or absent (parts of Europe, Africa). This study confirms that Beijing/W genotype TB is an emerging pathogen in several areas and a predominant endemic strain in others; it is frequently associated with drug resistance.
    • Benchtop NMR spectroscopy in the analysis of substandard and falsified medicines as well as illegal drugs.

      Keizers, Peter H J; Bakker, Frank; Ferreira, José; Wackers, Paul F K; van Kollenburg, Dion; van der Aa, Eva; van Beers, Amy (2019-10-21)
    • Benefits and challenges in using sero-prevalence data to inform models for measles and rubella elimination.

      Winter, A K; Martinez, M E; Cutts, F T; Moss, W J; Ferrari, M; McKee, A; Lessler, J; Hayford, K; Wallinga, J; Metcalf, C J E (2018-03-19)
      Control efforts for measles and rubella are intensifying globally. It becomes increasingly important to identify and reach remaining susceptible populations as elimination is approached. Serological surveys for measles and rubella can potentially measure susceptibility directly, but their use remains rare. Here, using simulations, we outline key subtleties in interpretation associated with the dynamic context of age-specific immunity, highlighting how the patterns of immunity predicted from disease surveillance and vaccination coverage data may be misleading. High quality representative sero-surveys could provide a more accurate assessment of immunity if challenges of conducting, analyzing, and interpreting them are overcome. We frame the core disease control and elimination questions that could be addressed by improved serological tools, discussing challenges and suggesting approaches to increase the feasibility and sustainability of the tool. Accounting for the dynamical context, sero-surveys could play a key role in efforts to achieve and sustain elimination.
    • Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol.

      Blankestijn, Peter J; Fischer, Kathrin I; Barth, Claudia; Cromm, Krister; Canaud, Bernard; Davenport, Andrew; Grobbee, Diederick E; Hegbrant, Jörgen; Roes, Kit C; Rose, Matthias; et al. (2020-02-05)
    • Best Paper Award.

      Peijnenburg, Willie J G M (2018-01-01)
    • Best practices for developmental toxicity assessment for classification and labeling.

      Daston, George; Piersma, Aldert; Attias, Leonello; Beekhuijzen, Manon; Chen, Connie; Foreman, Jennifer; Hallmark, Nina; Leconte, Isabelle (2018-05-14)
      Many chemicals are going through a hazard-based classification and labeling process in Europe. Because of the significant public health implications, the best science must be applied in assessing developmental toxicity data. The European Teratology Society and Health and Environmental Sciences Institute co-organized a workshop to consider best practices, including data quality and consistency, interpretation of developmental effects in the presence of maternal toxicity, human relevance of animal data, and limits of chemical classes. Recommendations included larger historical control databases, more pharmacokinetic studies in pregnant animals for dose setting and study interpretation, generation of mechanistic data to resolve questions about whether maternal toxicity is causative of developmental toxicity, and more rigorous specifications for what constitutes a chemical class. It is our hope that these recommendations will form the basis for subsequent consensus workshops and other scientific activities designed to improve the scientific robustness of data interpretation for classification and labeling.
    • Bestrijding van aviaire influenza onder pluimvee: vaccinatie als aanvullende mogelijkheid

      Aarle, P van; Breytenbach, J; Schueller, S (RIVM, 2006-08-01)
      Since mid-December 2003, highly pathogenic avian influenza (HPAI) has caused an epidemic in the Asian poultry sector and avian influenza cases have been reported in Europe, the Middle East and Africa. Human fatalities catapulted avian influenza into the public arena with fears of a possible global influenza pandemic in case the virus gains capacity to spread from human to human. What should be the way forward? The article describes control options and discusses the role vaccination can play in combating specifically under European conditions and in dynamic poultry markets in other countries.
    • Beter zicht op zeer zorgwekkende stoffen.

      Janssen, N; Bodar, C; Lindeijer, H; Duintjer, K (2019-07-08)
    • Better off at home? Effects of nursing home eligibility on costs, hospitalizations and survival.

      Bakx, Pieter; Wouterse, Bram; van Doorslaer, Eddy; Wong, Albert (2020-07-06)
    • Biennial Pattern of Rotavirus Gastroenteritis in The Netherlands and a Shifting Age Distribution Following a Low Rotavirus Season, 2010-2016.

      Verberk, Janneke D M; Pijnacker, Roan; Bruijning-Verhagen, Patricia; Franz, Eelco; Vennema, Harry; Hooiveld, Mariëtte; Hahné, Susan J M; de Melker, Hester E (2017-12-22)
      A hyper-endemic rotavirus season was expected after a low-endemic 2014 season in the Netherlands. Rotavirus detections were however similar in 2015 and lower in 2016 compared with 2010-2013. Gastroenteritis consultations rates were also similar in 2015, but the age-distribution shifted to older children due to an accumulation of non-infected children. Results indicate a possible shift to a biennial rotavirus pattern.
    • Bioavailability and phytotoxicity of rare earth metals to Triticum aestivum under various exposure scenarios.

      Gong, Bing; He, Erkai; Xia, Bing; Ying, Rongrong; Peijnenburg, Willie J G M; Liu, Yang; Qiu, Hao (2020-09-22)
      It is a daunting challenge to predict toxicity and accumulation of rare earth metals (REMs) in different exposure scenarios (e.g., varying water chemistry and metal combinations). Herein, we investigated the toxicity and uptake of La and Ce in the presence of various levels of Ca, Mg, Na, K, and at different pH values, as well as the combined effects of La and Ce in wheat Triticum aestivum. Major cations (Ca2+ and Mg2+) significantly mitigated the toxicity and accumulation of La3+/Ce3+. Toxicity and uptake of La, Ce, and La-Ce mixtures could be well quantified by the multi-metal biotic ligand model (BLM) and by the Langmuir-type uptake model with the consideration of the competitive effects of Ca2+ and Mg2+, with more than 85.1% of variations explained. The derived binding constants of Ca, Mg, La, and Ce to wheat root were respectively 3.87, 3.59, 6.97, and 6.48 on the basis of toxicity data, and 3.23, 2.84, 6.07, and 5.27 on the basis of uptake data. The use of the alternative WHAM-Ftox approach, requiring fewer model parameters than the BLM but with similar Akaike information criterion (AIC) values, successfully predicted the toxicity and accumulation of La/Ce as well as toxicity of La-Ce mixtures, with at least 76.4% of variations explained. However, caution should be taken when using this approach to explain the uptake of La-Ce mixtures. Our results provided promising tools for delineating REMs toxicity/uptake in the presence of other toxicity-modifying factors or in mixture scenarios.
    • The biodistribution and immuno-responses of differently shaped non-modified gold particles in zebrafish embryos.

      van Pomeren, M; Peijnenburg, W J G M; Vlieg, R C; van Noort, S J T; Vijver, M G (2019-02-04)
      Important questions raised in (nano)ecotoxicology are whether biodistribution of nanoparticles (NPs) is affected by particle shape and to what extent local adverse responses are subsequently initiated. For nanomedicine, these same questions become important when the labeled NPs lose the labeling. In this study, we investigated the biodistribution patterns of gold nanoparticles (AuNPs) as well as immune-related local and systemic sublethal markers of exposure and behavioral assessment. Hatched zebrafish embryos were exposed to four differently shaped non-coated AuNPs with comparable sizes: nanospheres, nanorods, nano-urchins, and nano-bipyramids. Shape-dependent trafficking of the particles resulted in a different distribution of the particles over the target organs. The differences across the distribution patterns indicate that the particles behave slightly different, although they eventually reach the same target organs - yet in different ratios. Mainly local induction of the immune system was observed, whereas systemic immune responses were not clearly visible. Macrophages were found to take AuNPs from the body fluid, be transferred into the veins and transported to digestive organs for clearance. No significant behavioral toxicological responses in zebrafish embryos were observed after exposure. The trafficking of the particles in the macrophages indicates that the particles are removed via the mononuclear phagocytic system. The different ratios in which the particles are distributed over the target organs indicate that the shape influences their behavior and eventually possibly the toxicity of the particles. The observed shape-dependent biodistribution patterns might be beneficial for shape-specific targeting in nanomedicine and stress the importance of incorporating shape-features in nanosafety assessment.
    • Biokinetics of Nanomaterials: the Role of Biopersistence.

      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. (2017-04)
      Nanotechnology risk management strategies and environmental regulations continue to rely on hazard and exposure assessment protocols developed for bulk materials, including larger size particles, while commercial application of nanomaterials (NMs) increases. In order to support and corroborate risk assessment of NMs for workers, consumers, and the environment it is crucial to establish the impact of biopersistence of NMs at realistic doses. In the future, such data will allow a more refined future categorization of NMs. Despite many experiments on NM characterization and numerous in vitro and in vivo studies, several questions remain unanswered including the influence of biopersistence on the toxicity of NMs. It is unclear which criteria to apply to characterize a NM as biopersistent. Detection and quantification of NMs, especially determination of their state, i.e., dissolution, aggregation, and agglomeration within biological matrices and other environments are still challenging tasks; moreover mechanisms of nanoparticle (NP) translocation and persistence remain critical gaps. This review summarizes the current understanding of NM biokinetics focusing on determinants of biopersistence. Thorough particle characterization in different exposure scenarios and biological matrices requires use of suitable analytical methods and is a prerequisite to understand biopersistence and for the development of appropriate dosimetry. Analytical tools that potentially can facilitate elucidation of key NM characteristics, such as ion beam microscopy (IBM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), are discussed in relation to their potential to advance the understanding of biopersistent NM kinetics. We conclude that a major requirement for future nanosafety research is the development and application of analytical tools to characterize NPs in different exposure scenarios and biological matrices.
    • Biological activities associated with the volatile compound 2,5-bis(1-methylethyl)-pyrazine.

      Janssens, Thierry K S; Tyc, Olaf; Besselink, Harrie; de Boer, Wietse; Garbeva, Paolina (2019-01-29)
      Pyrazines are 1,4- diazabenzene based volatile organic compounds and known for their broad-spectrum antimicrobial activity. In the present study we assessed the antimicrobial activity of 2,5-bis(1-methylethyl)-pyrazine, produced by Paenibacillus sp. AD87 during co-culture with Burkholderia sp. AD24. In addition, we were using transcriptional reporter assays in E. coli and mammalian cells to decipher the possible mode of action. Bacterial and mammalian luciferase reporter strains were deployed to elucidate antimicrobial and toxicological effects of 2,5-bis(1-methylethyl)-pyrazine. At high levels of exposure, 2,5-bis(1-methylethyl)-pyrazine exerted strong DNA damage response. At lower concentrations, cell-wall damage response was observed. The activity was corroborated by a general toxicity reporter assay in E. coli ΔampD, defective in peptidoglycan turnover. The maximum E. coli cell-wall stress activity was measured at a concentration close to the onset of the mammalian cytotoxicity, while other adverse outcome pathways, such as the activation of aryl hydrocarbon and estrogenic receptor, the p53 tumor suppressor, and the oxidative stress related Nrf2 transcription factor, were induced at elevated concentrations compared to the response of mammalian cells. Because of its broad-spectrum antimicrobial activity at lower concentrations and the relatively low mammalian toxicity, 2,5-bis(1-methylethyl)-pyrazine is a potential bio-based fumigant with possible applications in food industry, agriculture or logistics.
    • Biological sex influences antibody responses to routine vaccinations in the first year of life.

      Zimmermann, Petra; Perrett, Kirsten P; Ritz, Nicole; Flanagan, Katie L; Robins-Browne, Roy; van der Klis, Fiona R M; Curtis, Nigel (2019-07-10)
    • Biological significance of metals partitioned to subcellular fractions within earthworms (Aporrectodea caliginosa).

      Vijver, Martina G; Gestel, Cornelis A M van; Straalen, Nico M van; Lanno, Roman P; Peijnenburg, Willie J G M (2006-03-01)
      Metal ions in excess of metabolic requirements are potentially toxic and must be removed from the vicinity of important biological molecules to protect organisms from adverse effects. Correspondingly, metals are sequestrated in various forms, defining the accumulation pattern and the magnitude of steady-state levels reached. To investigate the subcellular fractions over which Ca, Mg, Fe, Cu, Zn, Cd, Pb, Ni, and As are distributed, earthworms (Aporrectodea caliginosa) collected from the field were analyzed by isolating metal-rich granules and tissue fragments from intracellular microsomal and cytosolic fractions (i.e., heat-stable proteins and heat-denatured proteins). The fractions showed metal-specific binding capacity. Cadmium was mainly retrieved from the protein fractions. Copper was equally distributed over the protein fraction and the fraction comprising tissue fragments, cell membranes, and intact cells. Zinc, Ca, Mg, and As were mainly found in this fraction as well. Lead, Fe, and Ni were mainly isolated from the granular fraction. To study accumulation kinetics in the different fractions, three experiments were conducted in which earthworms were exposed to metal-spiked soil and a soil contaminated by anthropogenic inputs and, indigenous earthworms were exposed to field soils. Although kinetics showed variation, linear uptake and steady-state types of accumulation patterns could be understood according to subcellular compartmentalization. For risk assessment purposes, subcellular distribution of metals might allow for a more precise estimate of effects than total body burden. Identification of subcellular partitioning appears useful in determining the biological significance of steady-state levels reached in animals.
    • Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies.

      Marklund, Matti; Wu, Jason H Y; Imamura, Fumiaki; Del Gobbo, Liana C; Fretts, Amanda; de Goede, Janette; Shi, Peilin; Tintle, Nathan; Wennberg, Maria; Aslibekyan, Stella; et al. (2019-04-11)
      Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15,198 incident cardiovascular events occurred among 68,659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI: 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower CHD risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; comparing extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
    • Biomonitoring as an Underused Exposure Assessment Tool in Occupational Safety and Health Context-Challenges and Way Forward.

      Viegas, Susana; Zare Jeddi, Maryam; B Hopf, Nancy; Bessems, Jos; Palmen, Nicole; S Galea, Karen; Jones, Kate; Kujath, Peter; Duca, Radu-Corneliu; Verhagen, Hans; et al. (2020-08-13)
    • Biomonitoring of Deoxynivalenol and Deoxynivalenol-3-glucoside in Human Volunteers: Renal Excretion Profiles.

      Mengelers, Marcel; Zeilmaker, Marco; Vidal, Arnau; De Boevre, Marthe; De Saeger, Sarah; Hoogenveen, Rudolf (2019-08-08)