• Bacitracin and gramicidin

      Murk, JL; Kluytmans, J (2018-12-04)
    • Bacteriën als wapen

      Vries MC de; Voordouw BCG; Reubsaet FAG (2017-06)
    • Bacteriological and Immunological Profiling of Meconium and Fecal Samples from Preterm Infants: A Two-Year Follow-Up Study.

      Gómez, Marta; Moles, Laura; Espinosa-Martos, Irene; Bustos, Gerardo; de Vos, Willem M; Fernández, Leónides; Rodríguez, Juan M; Fuentes, Susana; Jiménez, Esther (2017-11-27)
      An abnormal colonization pattern of the preterm gut may affect immune maturation and exert a long-term influence on the intestinal bacterial composition and host health. However, follow-up studies assessing the evolution of the fecal microbiota of infants that were born preterm are very scarce. In this work, the bacterial compositions of fecal samples, obtained from sixteen 2-year-old infants were evaluated using a phylogenetic microarray; subsequently, the results were compared with those obtained in a previous study from samples of meconium and feces collected from the same infants while they stayed in the neonatal intensive care unit (NICU). In parallel, the concentration of a wide range of cytokines, chemokines, growth factors and immunoglobulins were determined in meconium and fecal samples. Globally, a higher bacterial diversity and a lower interindividual variability were observed in 2-year-olds' feces, when compared to the samples obtained during their first days of life. Hospital-associated fecal bacteria, that were dominant during the NICU stay, seemed to be replaced, two years later, by genera, which are usually predominant in the healthy adult microbiome. The immune profile of the meconium and fecal samples differed, depending on the sampling time, showing different immune maturation statuses of the gut.
    • BAFF augments IgA2 and IL-10 production by TLR7/8 stimulated total peripheral blood B cells.

      den Hartog, Gerco; van Osch, Thijs L J; Vos, Martijn; Meijer, Ben; Savelkoul, Huub F J; van Neerven, R J Joost; Brugman, Sylvia (2017-09-17)
      Class-switching of B cells to IgA can be induced via both T-cell-dependent and T-cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T-cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection. To this end total and naive peripheral blood B cells were stimulated with these factors for 6 days in the presence or absence of TLR7/8 agonist R848 (mimicking viral infection) or TLR9 agonist CpG-ODN (mimicking bacterial infection). We show that BAFF significantly augments IgA2 production in TLR7/8 stimulated mature, but not naïve B cells. In addition, BAFF augments IL-10 production and viability in TLR7/8 and TLR9 stimulated mature B cells. These data warrant further investigation of its role in immune regulation both in the periphery and mucosal tissues in early life or during disease.
    • Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the Netherlands, January 2008 to December 2012.

      Gadroen, Kartini; Kemmeren, Jeanet M; Bruijning-Verhagen, Patricia Cj; Straus, Sabine Mjm; Weibel, Daniel; de Melker, Hester E; Sturkenboom, Miriam Cjm (2017-06-22)
      Intussusception is a rare, potentially life-threatening condition in early childhood. It gained attention due to an unexpected association with the first rotavirus vaccine, RotaShield, which was subsequently withdrawn from the market. Across Europe, broad variations in intussusception incidence rates have been reported. This study provides a first estimate of intussusception incidence in young children in the Netherlands from 1 January 2008 to 31 December 2012, which could be used for future rotavirus safety monitoring. Our estimates are based on two different sources: electronic medical records from the primary healthcare database (IPCI), as well as administrative data from the Dutch hospital register (LBZ). The results from our study indicate a low rate of intussusception. Overall incidence rate in children < 36 months of age was 21.2 per 100,000 person-years (95% confidence interval (CI): 12.5-34.3) based on primary healthcare data and 22.6 per 100,000 person-years (95% CI: 20.9-24.4) based on hospital administrative data. The estimates suggest the upper and lower bound of the expected number of cases.
    • BasinBox: a generic multimedia fate model for predicting the fate of chemicals in river catchments

      Hollander, A; Huijbregts, M A J; Ragas, A M J; Meent, D van de (Springer, 2006-05-20)
      Multimedia fate models have proven to be very useful tools in chemical risk assessment and management. This paper presents BasinBox, a newly developed steady-state generic multimedia fate model for evaluating risks of new and existing chemicals in river basins. The model concepts, as well as the intermedia processes quantified in the model, are outlined, and an overview of the required input parameters is given. To test the BasinBox model, calculations were carried out for predicting the fate of chemicals in the river Rhine basin. This was done for a set of 3175 hypothetical chemicals and three emission scenarios to air, river water and cropland soils. For each of these hypothetical chemicals and emission scenarios the concentration ratio between the downstream area and the upstream area was calculated for all compartments. From these calculations it appeared that BasinBox predicts significant concentration differences between upstream and downstream areas of the Rhine river basin for certain types of chemicals and emission scenarios. There is a clear trend of increasing chemical concentrations in downstream direction of the river basin. The calculations show that taking into account spatial variability between upstream, midstream and downstream areas of large river basins can be useful in the predictions of environmental concentrations by multimedia fate models.
    • A bead-based suspension array for the detection of Salmonella antibodies in pig sera.

      van der Wal, Fimme J; Achterberg, René P; Maassen, Catharina B M (2018-07-27)
      Slaughter pigs are monitored for the presence of the zoonotic pathogen Salmonella, using both serology and bacteriology. ELISAs used to investigate pig herds are based on the detection of antibodies against components of the Salmonella cell envelope. Nearly all Salmonella isolates in food-producing animals are serovars of Salmonella enterica subspecies enterica, distributed over various serogroups as determined by the composition of their lipopolysaccharide (LPS). ELISAs for Salmonella serology are usually based on serogroup B and C1 LPS, often combined with serogroup D or E LPS. Although C2 LPS may improve serology, use of C2 LPS in a broad ELISA was never achieved.
    • Bedaquiline resistance: Its emergence, mechanism and prevention.

      Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C (2017-11-08)
      Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678 and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed.Understanding any target and non-target based mechanisms is essential to minimize the resistance development and treatment failure, help to develop appropriate DST for bedaquiline and genetic based resistance screening.
    • 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.
    • 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.
    • Bescherming ozonlaag : 20 jaar effectief beleid - een welkome waarheid

      KNMI; MNP; RIVM (Koninklijk Nederlands Meteorologisch Instituut (KNMI), Milieu- en Natuurplanbureau (MNP),, 2007-09)
    • 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.
    • 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.
    • 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; Jungnickel, Harald; Kock, Heiko; Tentschert, Jutta; Tlili, Ahmed; Schäffer, Andreas; Sips, Adriënne J A M; Yokel, Robert A; Luch, Andreas (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 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.
    • Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate.

      Thambavita, Dhanusha; Galappatthy, Priyadarshani; Mannapperuma, Uthpali; Jayakody, Lal; Cristofoletti, Rodrigo; Abrahamsson, Bertil; Groot, Dirk W; Langguth, Peter; Mehta, Mehul; Parr, Alan; Polli, James E; Shah, Vinod P; Dressman, Jennifer (2017-10)
      Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release solid oral dosage forms containing amoxicillin trihydrate are reviewed. Solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), therapeutic uses, therapeutic index, excipient interactions, as well as dissolution and BE and bioavailability studies were taken into consideration. Solubility and permeability studies indicate that amoxicillin doses up to 875 mg belong to BCS class I, whereas 1000 mg belongs to BCS class II and doses of more than 1000 mg belong to BCS class IV. Considering all aspects, the biowaiver procedure can be recommended for solid oral products of amoxicillin trihydrate immediate-release preparations containing amoxicillin as the single active pharmaceutical ingredient at dose strengths of 875 mg or less, provided (a) only the excipients listed in this monograph are used, and only in their usual amounts, (b) the biowaiver study is performed according to the World Health Organization-, U.S. Food and Drug Administration-, or European Medicines Agency-recommended method using the innovator as the comparator, and (c) results comply with criteria for "very rapidly dissolving" or "similarly rapidly dissolving." Products containing other excipients and those containing more than 875 mg amoxicillin per unit should be subjected to an in vivo BE study.