44 research outputs found

    Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells

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    Background: Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC) as compared to wild-type (WT) cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM) and g-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts) after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU) and vehicle were taken as controls. Results: Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments. Conclusion: These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.Toxicogenomics and risk assessmen

    Perfusion measured by laser speckle contrast imaging as a predictor for expansion of psoriasis lesions

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    BACKGROUND: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI). OBJECTIVES: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality. METHODS: In this interventional pilot study in adults with unstable plaque psoriasis, HAPI measurements and color photographs were performed for lesions present on one body region at week 0, 2, 4, 6 and 8. The presence of increased perilesional perfusion and perfusion inhomogeneity was determined. Clinical outcome was categorized as increased, stable or decreased lesion surface between visits. Patient feedback was collected on a 10‐point scale. RESULTS: In total, 110 lesions with a median follow‐up of 6 (IQR 6.0) weeks were assessed in 6 patients with unstable plaque psoriasis. Perfusion data was matched to 281 clinical outcomes after two weeks. A mixed multinomial logistic regression model revealed a predictive value of perilesional increased perfusion (OR 9.90; p < 0.001) and perfusion inhomogeneity (OR 2.39; p = 0.027) on lesion expansion after two weeks compared to lesion stability. HAPI measurements were considered fast, patient‐friendly and important by patients. CONCLUSION: Visualization of increased perilesional perfusion and perfusion inhomogeneity by noninvasive whole field LSCI holds potential for prediction of psoriatic lesion expansion. Furthermore, the HAPI is a feasible and patient‐friendly tool

    Persistent ventilation inhomogeneity after an acute exacerbation in preschool children with recurrent wheezing

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    © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. Background: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. Methods: We recruited children between 3 and 6years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. Results: Seventy-four children, mean (standard deviation (SD)) age of 4.32years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age-dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P=.003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from −1.66 to −1.17 (P=.05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with “well-controlled” asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. Conclusions: Lung clearance index demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children

    Rice seed sector development in the Ayeyarwady Delta : Review of lessons learned

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    Programmeringsstudie klimaatbestendig landelijk en stedelijk gebied : Programmeringsstudie voor de kennis- en innovatie agenda Landbouw, Water, Voedsel

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    Deze programmeringsstudie is uitgevoerd in opdracht van het ministerie van LNV en levert een bijdrage aan de Kennis en Innovatie Agenda (KIA) voor het thema Landbouw, Water, Voedsel. De KIA is onderverdeeld in 6 missies, waarvan Klimaatbestendig Landelijk en Stedelijk (missie C) gebied er één van is. Het doel van missie C is om Nederland zowel voor het landelijke als stedelijk gebied uiterlijk in 2050 klimaatbestendig en waterrobuust te maken en te houden bij verdergaande klimaatverandering. In de programmeringsstudie zijn de belangrijkste kennis- en innovatieopgaven die nodig zijn om dit doel te bereiken uitgewerkt
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