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- Bosmans, Laura A., et al.
(författare)
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Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:5, s. 1146-1160
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Tidskriftsartikel (refereegranskat)abstract
- Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. Method and Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe−/− background were generated (CD40wt and CD40mac−/− , respect-Results ively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac−/− compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac−/− atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b− macrophages in the atherosclerotic aorta of CD40mac−/− compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac−/− mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). Conclusions We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.
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| 3. |
- Brasil, DM, et al.
(författare)
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Monitoring cone-beam CT radiation dose levels in a University Hospital
- 2023
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Ingår i: Dento maxillo facial radiology. - : British Institute of Radiology. - 0250-832X. ; 52:3, s. 20220213-
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Tidskriftsartikel (refereegranskat)abstract
- To present patient dose levels for different CBCT scanners, acquired by a dose monitoring tool in a University Hospital, as a function of field of view (FOV), operation mode, and patient age. Methods: An integrated dose monitoring tool was used to collect radiation exposure data [type of CBCT unit, dose-area product (DAP), FOV size, and operation mode] and patient demographic information (age, referral department) performed on a 3D Accuitomo 170 and a Newtom VGI EVO unit. Effective dose conversion factors were calculated and implemented into the dose monitoring system. For each CBCT unit, the frequency of examinations, clinical indications, and effective dose levels were obtained for different age and FOV groups, and operation modes. Results: A total of 5163 CBCT examinations were analyzed. Surgical planning and follow-up were the most frequent clinical indications. For the standard operation mode, effective doses ranged from 35.1 to 300 µSv and 9.26-117 µSv using 3D Accuitomo 170 and Newtom VGI EVO, respectively. In general, effective doses decreased with increasing age and FOV size reduction. Conclusions: Effective dose levels varied notably between systems and operation modes.Operation mode selection and FOV size were indication-oriented, with larger FOV sizes election serving surgical planning and follow-up. Seeing the influence of FOV size on effective dose levels, manufacturers could be advised to move toward patient-specific collimation and dynamic FOV selection. Systematically monitoring patient doses could be recommended for steering future CBCT optimization.
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