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- Boldock, Emma, et al.
(författare)
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Human skin commensals augment Staphylococcus aureus pathogenesis.
- 2018
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Ingår i: Nature microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 3:8, s. 881-90
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Tidskriftsartikel (refereegranskat)abstract
- All bacterial infections occur within a polymicrobial environment, from which a pathogen population emerges to establish disease within a host. Emphasis has been placed on prevention of pathogen dominance by competing microflora acting as probiotics1. Here we show that the virulence of the human pathogen Staphylococcus aureus is augmented by native, polymicrobial, commensal skin flora and individual species acting as 'proinfectious agents'. The outcome is pathogen proliferation, but not commensal. Pathogenesis augmentation can be mediated by particulate cell wall peptidoglycan, reducing the S. aureus infectious dose by over 1,000-fold. This phenomenon occurs using a range of S. aureus strains and infection models and is not mediated by established receptor-mediated pathways including Nod1, Nod2, Myd88 and the NLPR3 inflammasome. During mouse sepsis, augmentation depends on liver-resident macrophages (Kupffer cells) that capture and internalize both the pathogen and the proinfectious agent, leading to reduced production of reactive oxygen species, pathogen survival and subsequent multiple liver abscess formation. The augmented infection model more closely resembles the natural situation and establishes the role of resident environmental microflora in the initiation of disease by an invading pathogen. As the human microflora is ubiquitous2, its role in increasing susceptibility to infection by S. aureus highlights potential strategies for disease prevention.
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| 2. |
- Stock, M., et al.
(författare)
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Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group
- 2019
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 58:12, s. 1720-1730
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer. Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created. Results: For CTV1, the average D-median was 59.3 +/- 2.4 Gy(RBE) for protons and 58.8 +/- 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average D-median was 71.2 +/- 1.0 Gy(RBE) for protons and 70.6 +/- 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D-2% for the spinal cord was 25.1 +/- 8.5 Gy(RBE) for protons and 47.6 +/- 1.4 Gy(RBE) for VMAT. The average D-2% for chiasm was 46.5 +/- 4.4 Gy(RBE) for protons and 50.8 +/- 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams. Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.
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