43 research outputs found

    Basisvorming meertaligheid

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    Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

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    New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs

    Dynamic reciprocity of cell-matrix interactions in cancer invasion

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    Contains fulltext : 212655.pdf (publisher's version ) (Open Access)Radboud University, 18 december 2019Promotor : Friedl, P.H.A. Co-promotores : Zegers, M.M.P., Wolf, K.A

    Dynamic reciprocity of cell-matrix interactions in cancer invasion

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    Strain Stiffening of Fibrillar Collagen during Individual and Collective Cell Migration Identified by AFM Nanoindentation

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    The multistep process of cell migration requires cells to dynamically couple to extracellular interfaces and generate traction force or friction for displacement of the cell body. When deformed, biopolymer networks, including fibrillar collagen and fibrin, undergo a nonlinear elasticity change that is termed strain stiffening and is commonly measured by bulk rheology. It remains poorly characterized, however, whether forces generated by moving cells suffice to induce strain stiffening. To detect strain stiffening at the leading edge of normal and tumor cells moving across fibrillar type I collagen, we combined AFM nanoindentation and differential field probing with confocal reflection microscopy. In different cell models, gradient-like fiber realignment, densification, and elevation of Young's modulus ahead of the leading edge were observed, with peak increases of up to 1.15 kPa near the leading edge. Moving fibroblasts generated a larger anterograde strain field with a higher amplitude and up to 6-fold increased cumulative strain stiffening (52 kPa) compared with mesenchymal HT1080 fibrosarcoma cells (8.8 kPa) and epithelial SCC38 cancer cells (9.8 kPa). Collectively moving SCC38 cells produced 4-fold increased cumulative strain stiffening (38 kPa) compared with individually moving SCC38 cells in a beta1 integrin- and actomyosin-dependent manner. This indicates that the extent of strain stiffening by the leading edge of moving cells scales with cell type, multicellular cooperativity, integrin availability, and contractility. By straining, migrating cells realign and densify fibrillar extracellular matrix and thus adopt an autonomous strategy to move on a "traveling wave" of stiffened substrate, which reaches levels sufficient for mechanosensory activation and self-steering of migration

    Basisvorming meertaligheid

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