• Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report.

      Hoornenborg, Elske; Prins, Maria; Achterbergh, Roel C A; Woittiez, Lycke R; Cornelissen, Marion; Jurriaans, Suzanne; Kootstra, Neeltje A; Anderson, Peter L; Reiss, Peter; de Vries, Henry J C; et al. (2017-11)
      Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate.
    • An across-species comparison of the sensitivity of different organisms to Pb-based perovskites used in solar cells.

      Wang, Guiyin; Zhai, Yujia; Zhang, Shirong; Diomede, Luisa; Bigini, Paolo; Romeo, Margherita; Cambier, Sebastien; Contal, Servane; Nguyen, Nhung H A; Rosická, Petra; et al. (2020-03-15)
      Organic-inorganic perovskite solar cells (PSCs) are promising candidates as photovoltaic cells. Recently, they have attracted significant attention due to certified power conversion efficiencies exceeding 23%, low-cost engineering, and superior electrical/optical characteristics. These PSCs extensively utilize a perovskite-structured composite with a hybrid of Pb-based nanomaterials. Operation of them may cause the release of Pb-based nanoparticles. However, limited information is available regarding the potential toxicity of Pb-based PSCs on various organisms. This study conducted a battery of in vitro and in vivo toxicity bioassays for three quintessential Pb-based PSCs (CH3NH3PbI3, NHCHNH3PbBr3, and CH3NH3PbBr3) using progressively more complex forms of life. For all species tested, the three different perovskites had comparable toxicities. The viability of Caco-2/TC7 cells was lower than that of A549 cells in response to Pb-based PSC exposure. Concentration-dependent toxicity was observed for the bioluminescent bacterium Vibrio fischeri, for soil bacterial communities, and for the nematode Caenorhabditis elegans. Neither of the tested Pb-based PSCs particles had apparent toxicity to Pseudomonas putida. Among all tested organisms, V. fischeri showed the highest sensitivity with EC50 values (30 min of exposure) ranging from 1.45 to 2.91 mg L-1. Therefore, this study recommends that V. fischeri should be preferably utilized to assess. PSC toxicity due to its increased sensitivity, low costs, and relatively high throughput in a 96-well format, compared with the other tested organisms. These results highlight that the developed assay can easily predict the toxic potency of PSCs. Consequently, this approach has the potential to promote the implementation of the 3Rs (Replacement, Reduction, and Refinement) principle in toxicology and decrease the dependence on animal testing when determining the safety of novel PSCs.
    • Activation of Human Monocytes by Colloidal Aluminum Salts.

      Vrieling, Hilde; Kooijman, Sietske; de Ridder, Justin W; Thies-Weesie, Dominique M E; Soema, Peter C; Jiskoot, Wim; van Riet, Elly; Heck, Albert J R; Philipse, Albert P; Kersten, Gideon F A; et al. (2019-08-23)
    • Activation of Human NK Cells by Requires Inflammasome Activation in Macrophages.

      Kroes, Michiel M; Mariman, Rob; Hijdra, Daniëlle; Hamstra, Hendrik-Jan; van Boxtel, Karlijn J W M; van Putten, Jos P M; de Wit, Jelle; Pinelli, Elena (2019-01-01)
      Pertussis is a highly contagious respiratory infection caused by the bacterium Bordetella pertussis. Humans are the only known natural reservoir of B. pertussis. In mice, macrophages and NK cells have a key role in confining B. pertussis to the respiratory tract. However, the mechanisms underlying this process, particularly during human infections, remain unclear. Here we characterized the activation of human macrophages and NK cells in response to B. pertussis and unraveled the role of inflammasomes in this process. NLRP3 inflammasome activation by B. pertussis in human macrophage-like THP-1 cells and primary monocyte-derived macrophages (mo-MΦ) was shown by the visualization of ASC-speck formation, pyroptosis, and the secretion of caspase-mediated IL-1β and IL-18. In contrast to macrophages, stimulation of human CD56+CD3- NK cells by B. pertussis alone did not result in activation of these cells. However, co-culture of B. pertussis-stimulated mo-MΦ and autologous NK cells resulted in high amounts of IFNγ secretion and an increased frequency of IL-2Rα+ and HLA-DR+ NK cells, indicating NK cell activation. This activation was significantly reduced upon inhibition of inflammasome activity or blocking of IL-18 in the mo-MΦ/NK cell co-culture. Furthermore, we observed increased secretion of proinflammatory cytokines in the B. pertussis-stimulated mo-MΦ/NK co-culture compared to the mo-MΦ single culture. Our results demonstrate that B. pertussis induces inflammasome activation in human macrophages and that the IL-18 produced by these cells is required for the activation of human NK cells, which in turn enhances the pro-inflammatory response to this pathogen. Our data provides a better understanding of the underlying mechanisms involved in the induction of innate immune responses against B. pertussis. These findings contribute to the knowledge required for the development of improved intervention strategies to control this highly contagious disease.
    • Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era.

      Gupta, R K; Lipman, M; Story, A; Hayward, A; de Vries, G; van Hest, R; Erkens, C; Rangaka, M X; Abubakar, I (2018-05-01)
      Vulnerable populations, including homeless persons, high-risk drug and alcohol users, prison inmates and other marginalised populations, contribute a disproportionate burden of tuberculosis (TB) cases in low-incidence settings. Drivers of this disease burden include an increased risk of both TB transmission in congregate settings, and progression from infection to active disease. Late diagnosis and poor treatment completion further propagate the epidemic and fuel the acquisition of drug resistance. These groups are therefore a major priority for TB control programmes in low-incidence settings. Targeted strategies include active case finding (ACF) initiatives and interventions to improve treatment completion, both of which should be tailored to local populations. ACF usually deploys mobile X-ray unit screening, which allows sensitive, high-throughput screening with immediate availability of results. Such initiatives have been found to be effective and cost-effective, and associated with reductions in proxy measures of transmission in hard-to-reach groups. The addition of point-of-care molecular diagnostics and automated X-ray readers may further streamline the screening pathway. There is little evidence to support interventions to improve adherence among these risk groups. Such approaches include enhanced case management and directly observed treatment, while video-observed therapy (currently under evaluation) appears to be a promising tool for the future. Integrating outreach services to include both case detection and case-management interventions that share a resource infrastructure may allow cost-effectiveness to be maximised. Integrating screening and treatment for other diseases that are prevalent among targeted risk groups into TB outreach interventions may further improve cost-effectiveness. This article reviews the existing literature, and highlights priorities for further research.
    • Active commuting through natural environments is associated with better mental health: Results from the PHENOTYPE project.

      Zijlema, Wilma L; Avila-Palencia, Ione; Triguero-Mas, Margarita; Gidlow, Christopher; Maas, Jolanda; Kruize, Hanneke; Andrusaityte, Sandra; Grazuleviciene, Regina; Nieuwenhuijsen, Mark J (2018-12)
      Commuting routes with natural features could promote walking or cycling for commuting. Commuting through natural environments (NE) could have mental health benefits as exposure to NE can reduce stress and improve mental health, but there is little evidence. This study evaluates the association between NE and commuting, whether active or not, and the association between commuting (through NE), whether active or not, and mental health. We also evaluate the moderating effect of NE quality on the association between NE commuting and mental health.
    • Acute Gastroenteritis Disease Burden in Infants With Medical Risk Conditions in the Netherlands.

      van Dongen, Josephine A P; Rouers, Elsbeth D M; Schuurman, Rob; Bonten, Marc J M; Bruijning-Verhagen, Patricia (2020-11-18)
    • Acute hepatitis C infection among adults with HIV in the Netherlands between 2003 and 2016: a capture-recapture analysis for the 2013 to 2016 period.

      Boender, T Sonia; Op de Coul, Eline; Arends, Joop; Prins, Maria; van der Valk, Marc; van der Meer, Jan T M; van Benthem, Birgit; Reiss, Peter; Smit, Colette (2020-02-01)
    • Acute illness from Campylobacter jejuni may require high doses while infection occurs at low doses.

      Teunis, Peter F M; Bonačić Marinović, Axel; Tribble, David R; Porter, Chad K; Swart, Arno (2018-02-08)
      Data from a set of different studies on the infectivity and pathogenicity of Campylobacter jejuni were analyzed with a multilevel model, allowing for effects of host species (nonhuman primates and humans) and different strains of the pathogen. All challenge studies involved high doses of the pathogen, resulting in all exposed subjects to become infected. In only one study a dose response effect (increasing trend with dose) for infection was observed. High susceptibility to infection with C. jejuni was found in a joint analysis of outbreaks and challenge studies. For that reason four outbreaks, associated with raw milk consumption, were also included in the present study. The high doses used for inoculation did not cause all infected subjects to develop acute enteric symptoms. The observed outcomes are consistent with a dose response effect for acute symptoms among infected subjects: a conditional illness dose response relation. Nonhuman primates and human volunteers did not appear to have different susceptibilities for developing enteric symptoms, but exposure in outbreaks (raw milk) did lead to a higher probability of symptomatic campylobacteriosis.
    • Acute Otitis Media During Infancy: Parent-reported Incidence and Modifiable Risk Factors.

      Prins-van Ginkel, Annemarijn C; Bruijning-Verhagen, Patricia C J; Uiterwaal, Cuno S P M; van der Ent, Cornelis K; Smit, Henriette A; de Hoog, Marieke L A (2017-03)
      Age at exposure to acute otitis media (AOM) risk factors such as day care attendance, lack of breastfeeding and tobacco smoke is little studied but important for targeting AOM prevention strategies. Moreover, studies are typically restricted to clinically diagnosed AOM, while a significant subset can occur outside the health care system, depending on the country setting. This study aims to determine risk factor exposure and effect of its timing within the first year of life on parent-reported AOM symptom episodes.
    • Adaptation of Bordetella pertussis to the respiratory tract.

      van Beek, Lucille L F; de Gouw, Daan D; Eleveld, Marc M J; Bootsma, Hester H J; de Jonge, Marien M I; Mooi, Frits F R; Zomer, Aldert A; Diavatopoulos, Dimitri D A (2018-03-08)
      There is a lack of insight into the basic mechanisms by which Bordetella pertussis adapts to the local host environment during infection. We analysed B. pertussis gene expression in the upper and lower airways of mice and compared this to SO4-induced in vitro Bvg-regulated gene transcription. Approximately 30% of all genes were found to be differentially expressed between in vitro vs. in vivo conditions. This included several novel potential vaccine antigens that were exclusively expressed in vivo. Significant differences in expression profile and metabolic pathways were identified between the upper versus the lower airways, suggesting distinct antigenic profiles. We found high expression of several Bvg-repressed genes during infection and mouse vaccination experiments using purified protein fractions from both Bvg- and Bvg+ cultures demonstrated protection against intranasal B. pertussis challenge. This study provides novel insights into the in vivo adaptation of B. pertussis and may facilitate the improvement of pertussis vaccines.
    • Adapting Citizen Science to Improve Health in an Occupational Setting: Preliminary Results of a Qualitative Study.

      van den Berge, Mandy; Hulsegge, Gerben; van der Molen, Henk F; Proper, Karin I; Pasman, H Roeline W; den Broeder, Lea; Tamminga, Sietske J; Hulshof, Carel T J; van der Beek, Allard J (2020-07-08)
    • Added Value of Serum Hormone Measurements in Risk Prediction Models for Breast Cancer for Women Not Using Exogenous Hormones: Results from the EPIC Cohort.

      Hüsing, Anika; Fortner, Renée T; Kühn, Tilman; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnes; Boeing, Heiner; et al. (2017-08-01)
      Purpose: Circulating hormone concentrations are associated with breast cancer risk, with well-established associations for postmenopausal women. Biomarkers may represent minimally invasive measures to improve risk prediction models.Experimental Design: We evaluated improvements in discrimination gained by adding serum biomarker concentrations to risk estimates derived from risk prediction models developed by Gail and colleagues and Pfeiffer and colleagues using a nested case-control study within the EPIC cohort, including 1,217 breast cancer cases and 1,976 matched controls. Participants were pre- or postmenopausal at blood collection. Circulating sex steroids, prolactin, insulin-like growth factor (IGF) I, IGF-binding protein 3, and sex hormone-binding globulin (SHBG) were evaluated using backward elimination separately in women pre- and postmenopausal at blood collection. Improvement in discrimination was evaluated as the change in concordance statistic (C-statistic) from a modified Gail or Pfeiffer risk score alone versus models, including the biomarkers and risk score. Internal validation with bootstrapping (1,000-fold) was used to adjust for overfitting.Results: Among women postmenopausal at blood collection, estradiol, testosterone, and SHBG were selected into the prediction models. For breast cancer overall, model discrimination after including biomarkers was 5.3 percentage points higher than the modified Gail model alone, and 3.4 percentage points higher than the Pfeiffer model alone, after accounting for overfitting. Discrimination was more markedly improved for estrogen receptor-positive disease (percentage point change in C-statistic: 7.2, Gail; 4.8, Pfeiffer). We observed no improvement in discrimination among women premenopausal at blood collection.Conclusions: Integration of hormone measurements in clinical risk prediction models may represent a strategy to improve breast cancer risk stratification. Clin Cancer Res; 23(15); 4181-9. ©2017 AACR.
    • The added value of using the HEPA PAT for physical activity policy monitoring: a four-country comparison.

      Gelius, Peter; Messing, Sven; Forberger, Sarah; Lakerveld, Jeroen; Mansergh, Fiona; Wendel-Vos, Wanda; Zukowska, Joanna; Woods, Catherine (2021-02-15)
    • Additional Evidence on Serological Correlates of Protection against Measles: An Observational Cohort Study among Once Vaccinated Children Exposed to Measles.

      Woudenberg, Tom; van Binnendijk, Rob; Veldhuijzen, Irene; Woonink, Frits; Ruijs, Helma; van der Klis, Fiona; Kerkhof, Jeroen; de Melker, Hester; de Swart, Rik; Hahné, Susan (2019-10-22)
    • Addressing safety risks in integrated care programs for older people living at home: a scoping review.

      Lette, Manon; Ambugo, Eliva A; Hagen, Terje P; Nijpels, Giel; Baan, Caroline A; De Bruin, Simone R (2020-02-28)
    • Adenine base editing of the polyadenylation signal for targeted genetic therapy in facioscapulohumeral muscular dystrophy.

      Šikrová, Darina; Cadar, Vlad A; Ariyurek, Yavuz; Laros, Jeroen F J; Balog, Judit; van der Maarel, Silvère M (2021-06-01)
      Facioscapulohumeral muscular dystrophy (FSHD) is caused by chromatin relaxation of the D4Z4 repeat resulting in misexpression of the D4Z4-encoded DUX4 gene in skeletal muscle. One of the key genetic requirements for the stable production of full-length DUX4 mRNA in skeletal muscle is a functional polyadenylation signal (ATTAAA) in exon three of DUX4 that is used in somatic cells. Base editors hold great promise to treat DNA lesions underlying genetic diseases through their ability to carry out specific and rapid nucleotide mutagenesis even in postmitotic cells such as skeletal muscle. In this study, we present a simple and straightforward strategy for mutagenesis of the somatic DUX4 polyadenylation signal by adenine base editing in immortalized myoblasts derived from independent FSHD-affected individuals. We show that mutating this critical cis-regulatory element results in downregulation of DUX4 mRNA and its direct transcriptional target genes. Our findings identify the somatic DUX4 polyadenylation signal as a therapeutic target and represent the first step toward clinical application of the CRISPR-Cas9 base editing platform for FSHD gene therapy.
    • Adherence to a food group-based dietary guideline and incidence of prediabetes and type 2 diabetes.

      den Braver, Nicolette R; Rutters, Femke; van der Spek, Andrea L J Kortlever; Ibi, Dorina; Looman, Moniek; Geelen, Anouk; Elders, Petra; van der Heijden, Amber A; Brug, Johannes; Lakerveld, Jeroen; et al. (2019-07-24)
      During a mean follow-up of 6.3 ± 0.7 years, 837 participants developed preT2D and 321 participants developed T2D. The highest adherence to the DHD15-index was significantly associated with lower T2D incidence [model 3, PRT3vsT1: 0.70 (0.53; 0.92), ptrend = 0.01]. The highest adherence to the DHD15-index pointed towards a lower incidence of preT2D [PRT3vsT1: 0.87 (0.74; 1.03), ptrend = 0.11]. Higher adherence to the DHD15-index was not associated with change in fasting plasma glucose levels [β10point: - 0.012 (- 0.034; 0.009)mmol/L].
    • Adherence to dietary guidelines and cognitive decline from middle age: the Doetinchem Cohort Study.

      Nooyens, Astrid C J; Yildiz, Berivan; Hendriks, Lisa G; Bas, Sharell; van Boxtel, Martin P J; Picavet, H Susan J; Boer, Jolanda M A; Verschuren, W M Monique (2021-05-18)
    • Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort.

      Harbers, Marjolein C; de Kroon, A Marleen; Boer, Jolanda M A; Asselbergs, Folkert W; Geleijnse, Johanna M; Verschuren, W M Monique; van der Schouw, Yvonne T; Sluijs, Ivonne (2020-01-07)
      The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1-16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HRQ4vsQ1 0.73; 95% CI 0.58-0.93; Ptrend 0.001).