• Use of targeted mobile X-ray screening and computer-aided detection software to identify tuberculosis among high-risk groups in Romania: descriptive results of the E-DETECT TB active case-finding project.

      Mahler, Beatrice; de Vries, Gerard; van Hest, Rob; Gainaru, Dan; Menezes, Dee; Popescu, Gilda; Story, Alistair; Abubakar, Ibrahim (2021-08-24)
    • Occurrence of tick-borne pathogens in questing Ixodes ricinus ticks from Wester Ross, Northwest Scotland.

      Olsthoorn, Fanny; Sprong, Hein; Fonville, Manoj; Rocchi, Mara; Medlock, Jolyon; Gilbert, Lucy; Ghazoul, Jaboury (2021-08-26)
    • Applicability of organ-on-chip systems in toxicology and pharmacology.

      Schneider, Marlon R; Oelgeschlaeger, Michael; Burgdorf, Tanja; van Meer, Peter; Theunissen, Peter; Kienhuis, Anne S; Piersma, Aldert H; Vandebriel, Rob J (2021-08-31)
      Organ-on-chip (OoC) systems are microfabricated cell culture devices designed to model functional units of human organs by harboring an in vitro generated organ surrogate. In the present study, we reviewed issues and opportunities related to the application of OoC in the safety and efficacy assessment of chemicals and pharmaceuticals, as well as the steps needed to achieve this goal. The relative complexity of OoC over simple in vitro assays provides advantages and disadvantages in the context of compound testing. The broader biological domain of OoC potentially enhances their predictive value, whereas their complexity present issues with throughput, standardization and transferability. Using OoCs for regulatory purposes requires detailed and standardized protocols, providing reproducible results in an interlaboratory setting. The extent to which interlaboratory standardization of OoC is feasible and necessary for regulatory application is a matter of debate. The focus of applying OoCs in safety assessment is currently directed to characterization (the biology represented in the test) and qualification (the performance of the test). To this aim, OoCs are evaluated on a limited scale, especially in the pharmaceutical industry, with restricted sets of reference substances. Given the low throughput of OoC, it is questionable whether formal validation, in which many reference substances are extensively tested in different laboratories, is feasible for OoCs. Rather, initiatives such as open technology platforms, and collaboration between OoC developers and risk assessors may prove an expedient strategy to build confidence in OoCs for application in safety and efficacy assessment.
    • Decreased production of epithelial-derived antimicrobial molecules at mucosal barriers during early life.

      Lokken-Toyli, Kristen L; de Steenhuijsen Piters, Wouter A A; Zangari, Tonia; Martel, Rachel; Kuipers, Kirsten; Shopsin, Bo; Loomis, Cynthia; Bogaert, Debby; Weiser, Jeffrey N (2021-08-31)
    • Hepatitis B screening among immigrants: How to successfully reach the Moroccan community.

      Hamdiui, Nora; Steenbergen, Jim van; Rocha, Luis E C; Meiberg, Annemarie; Urbanus, Anouk; Hammou, Nadia Ait; Muijsenbergh, Maria van den; Timen, Aura; Stein, Mart L (2021-09-01)
    • Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis.

      Strak, Maciej; Weinmayr, Gudrun; Rodopoulou, Sophia; Chen, Jie; de Hoogh, Kees; Andersen, Zorana J; Atkinson, Richard; Bauwelinck, Mariska; Bekkevold, Terese; Bellander, Tom; et al. (2021-09-01)
      325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon.
    • Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses.

      van Tuijl, Lonneke A; Voogd, Adri C; de Graeff, Alexander; Hoogendoorn, Adriaan W; Ranchor, Adelita V; Pan, Kuan-Yu; Basten, Maartje; Lamers, Femke; Geerlings, Mirjam I; Abell, Jessica G; et al. (2021-09-02)
    • How the disruption in STI care due to the COVID-19 pandemic could lead to increased STI transmission among MSM in the Netherlands: a mathematical modelling study.

      Xiridou, Maria; Heijne, Janneke; Adam, Philippe; Op de Coul, Eline; Matser, Amy; de Wit, John; Wallinga, Jacco; van Benthem, Birgit (2021-08-31)
    • Identifying STI risk groups based on behavioral and psychological characteristics among heterosexuals during the COVID-19 pandemic.

      van Wees, Daphne A; Godijk, Noortje G; den Daas, Chantal; Kretzschmar, Mirjam E E; Heijne, Janneke C M (2021-08-31)
    • Menstrual blood CD146 mesenchymal stem cells reduced fibrosis rate in the rat model of premature ovarian failure.

      Yamchi, Nahideh Nazdikbin; Rahbarghazi, Reza; Bedate, Alberto Miranda; Mahdipour, Mahdi; Nouri, Mohammad; Khanbabaee, Ramazan (2021-09-03)
      Here, the regenerative potential of menstrual blood-derived mesenchymal stem cells (MenSCs) was examined on restoration of premature ovarian failure (POF) ovaries in rats' POF model. Freshly isolated CD146+ MenSCs using magnetic-activated cell storing method were immediately injected into ovaries of POF rats. Four and eight weeks after cell administration, both ovarian tissues were sampled for histological examination and the expression of fibrosis-related genes. Serum samples were also prepared for hormonal analysis. At the endpoint, mating trials were performed to assess the fertility of POF rats following MenSC transplantation. Histopathological examination revealed the induction of POF after Ceftriaxone injection by increasing atretic follicles and abnormal morphologies. MenSCs transplantation increased the number of normal follicles and coincided with the reduction of follicular atresia. Biochemical analyses exhibited the reduction and increase of systemic follicle-stimulating hormone (FSH) and E2 respectively after MenSCs transplantation compared to the POF rats (P < .05). No significant differences in anti-mullerian hormone (AMH) blood levels were detected in this study between POF controls and MenSCs-treated rats. We noted moreover the transcriptional up-regulation of Smad 2, 4, and TGF-β1 in POF rats, and these values were decreased after MenSCs transplantation (P < .01). By contrast, the RNA expression of Smad 6 remained increased in both pre- and post-treatment with MenSCs groups (P < .05). Finally, we found an increase in neonate births in POF rats treated with MenSCs, and that this feature was associated with ovarian rejuvenation through amelioration of fibrosis. These data showed that MenSCs are promising cell lineage for the alleviation of POF in the rat model by controlling the fibrosis rate.
    • Predictive factors for vaccine failure to guide vaccination in allogeneic hematopoietic stem cell transplant recipients.

      Janssen, Michelle J M; Bruns, Anke H W; Verduyn Lunel, Frans M; Raijmakers, Reinier A P; de Weijer, Roel J; Nanlohy, Nening M; Smits, Gaby P; van Baarle, Debbie; Kuball, Jürgen (2021-08-20)
      Vaccination after hematopoietic stem cell transplantation (HSCT) is essential to protect high-risk patients against potentially lethal infections. Though multiple studies have evaluated vaccine specific responses, no comprehensive analysis of a complete vaccination schedule post-HSCT has been performed and little is known about predictors for vaccine failure. In this context, allogeneic HSCT (alloHSCT) patients were included and vaccinated starting one year post-transplantation. Antibody responses were measured by Multiplex Immuno Assay for pneumococcal (PCV13), meningococcal C, diphtheria, pertussis, tetanus and Haemophilus influenza type b one month after the last vaccination and correlated to clinical and immunological parameters. Vaccine failure was defined as antibody response above vaccine-specific cut-off values for less than four out of six vaccines. Ninety-six patients were included of which 27.1% was found to have vaccine failure. Only 40.6% of all patients responded adequately to all six vaccines. In multivariate analysis, viral reactivation post-HSCT (OR 6.53; P = 0.03), B-cells <135 per mm3 (OR 7.24; P = 0.00) and NK-cells <170 per mm3 (OR 11.06; P = 0.00) were identified as predictors for vaccine failure for vaccination at one year post-alloHSCT. Measurement of antibody responses and an individualized approach for revaccination guided by clinical status and immune reconstitution of B-cells and NK-cells may improve vaccine responses.
    • Commentary: Development of a Comparative European Orthohantavirus Microneutralization Assay With Multi-Species Validation and Evaluation in a Human Diagnostic Cohort.

      Clement, Jan; Groen, Jan; van der Groen, Guido; Van Ranst, Marc; Maes, Piet; Osterhaus, Albertus D M E (2021-08-04)
    • Delineation of the exposure-response causality chain of chronic copper toxicity to the zebra mussel, Dreissena polymorpha, with a TK-TD model based on concepts of biotic ligand model and subcellular metal partitioning model.

      Le, T T Yen; Milen, Nachev; Grabner, Daniel; Hendriks, A Jan; Peijnenburg, Willie J G M; Sures, Bernd (2021-08-18)
      A toxicokinetic-toxicodynamic model was constructed to delineate the exposure-response causality. The model could be used: to predict metal accumulation considering the influence of water chemistry and biotic ligand characteristics; to simulate the dynamics of subcellular partitioning considering metabolism, detoxification, and elimination; and to predict chronic toxicity as represented by biomarker responses from the concentration of metals in the fraction of potentially toxic metal. The model was calibrated with data generated from an experiment in which the Zebra mussel Dreissena polymorpha was exposed to Cu at nominal concentrations of 25 and 50 μg/L and with varied Na+ concentrations in water up to 4.0 mmol/L for 24 days. Data used in the calibration included physicochemical conditions of the exposure environment, Cu concentrations in subcellular fractions, and oxidative stress-induced responses, i.e. glutathione-S-transferase activity and lipid peroxidation. The model explained the dynamics of subcellular Cu partitioning and the effect mechanism reasonably well. With a low affinity constant for Na + binding to Cu2+ uptake sites, Na + had limited influence on Cu2+ uptake at low Na+ concentrations in water. Copper was taken up into the metabolically available pool (MAP) at a largely higher rate than into the cellular debris. Similar Cu concentrations were found in these two fractions at low exposure levels, which could be attributed to sequestration pathways (metabolism, detoxification, and elimination) in the MAP. However, such sequestration was inefficient as shown by similar Cu concentrations in detoxified fractions with increasing exposure level accompanied by the increasing Cu concentration in the MAP.
    • Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients.

      Dent, M P; Vaillancourt, E; Thomas, R S; Carmichael, P L; Ouedraogo, G; Kojima, H; Barroso, J; Ansell, J; Barton-Maclaren, T S; Bennekou, S H; et al. (2021-08-10)
    • Circulation of Bordetella pertussis in the Caribbean Netherlands: a population-based seroepidemiological study.

      Immink, Maarten M; Vos, Eric R A; Janga-Jansen, Alcira V A; Baboe-Kalpoe, Sharda; Hulshof, Koen; van Vliet, Jeffrey; Kerkhof, Jeroen; den Hartog, Gerco; de Melker, Hester E; van der Klis, Fiona R M; et al. (2021-08-15)
    • Do we need to change catheter-related bloodstream infection surveillance in the Netherlands? A qualitative study among infection prevention professionals.

      Verberk, Janneke Dm; van der Kooi, Tjallie Ii; Derde, Lennie Pg; Bonten, Marc Jm; de Greeff, Sabine C; van Mourik, Maaike Sm (2021-08-18)
    • Developing the building blocks to elucidate the impact of the urban exposome on cardiometabolic-pulmonary disease: The EU EXPANSE project.

      Vlaanderen, Jelle; de Hoogh, Kees; Hoek, Gerard; Peters, Annette; Probst-Hensch, Nicole; Scalbert, Augustin; Melén, Erik; Tonne, Cathryn; de Wit, G Ardine; Chadeau-Hyam, Marc; et al. (2021-07-01)
    • Molecular neural crest cell markers enable discrimination of organophosphates in the murine cardiac embryonic stem cell test.

      Mennen, R H; Hallmark, N; Pallardy, M; Bars, R; Tinwell, H; Piersma, A H (2021-07-31)
      The cardiac embryonic stem cell test (ESTc) originally used the differentiation of beating cardiomyocytes for embryotoxicity screenings of compounds. However, the ESTc consists of a heterogeneous cell population, including neural crest (NC) cells, which are important contributors to heart development in vivo. Molecular markers for NC cells were investigated to explore if this approach improved discrimination between structurally related chemicals, using the three organophosphates (OP): chlorpyrifos (CPF), malathion (MLT), and triphenyl phosphate (TPP). To decrease the test duration and to improve the objective quantification of the assay read-out, gene transcript biomarkers were measured on study day 4 instead of the traditional cardiomyocyte beating assessment at day 10. Gene expression profiling and immunocytochemistry were performed using markers for pluripotency, proliferation and cardiomyocyte and NC differentiation. Cell proliferation was also assessed by measurements of embryoid body (EB) size and total protein quantification (day 7). Exposure to the OPs resulted in similar patterns of inhibition of beating cardiomyocyte differentiation and of myosin protein expression on day 10. However, these three chemically related compounds induced distinctive effects on NC cell differentiation, indicated by changes in expression levels of the NC precursor (Msx2), NC marker (Ap2α), and epithelial to mesenchymal transition (EMT; Snai2) gene transcripts. This study shows that investigating NC markers can provide added value for ESTc outcome profiling and may enhance the applicability of this assay for the screening of structurally related test chemicals.