We demonstrate excitation of photosensitisers (PSs) by accelerated protons to produce fluorescence and singlet oxygen. Their fluorescence follows a pattern similar to the proton energy loss in ...matter, while proton-derived fluorescence spectra match the photon-induced spectra. PSs excited in dry gelatin exhibit enhanced phosphorescence, suggesting an efficient PSs triplet state population. Singlet oxygen measurements, both optically at ~1270 nm and through the photoproduct of protoporphyrin IX (PpIX), demonstrate cytotoxic singlet oxygen generation by proton excitation. The singlet oxygen-specific scavenger 1,4-diazabicyclo2.2.2octane (DABCO) abrogates the photoproduct formation under proton excitation, but cannot countermand the overall loss of PpIX fluorescence. Furthermore, in two cell lines, M059K and T98G, we observe differential cell death upon the addition of the PS cercosporin, while in U87 cells we see no effect at any proton irradiation dose. Our results pave the way for a novel treatment combining proton therapy and "proton-dynamic therapy" for more efficient tumour eradication.
The Oslo Cyclotron Laboratory Görgen, A.; Guttormsen, M.; Larsen, A. C. ...
European physical journal plus,
02/2021, Letnik:
136, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Research at the Oslo Cyclotron Laboratory at the University of Oslo is focused on spectroscopy experiments for nuclear structure and nuclear astrophysics using the Oslo Scintillator Array OSCAR. ...Light-ion beams from the
K
=
35
cyclotron are furthermore used for studies in radiation biology and medical physics, for research and development related to medical isotope production, and for irradiation of materials and electronics components. Here we present an overview of the laboratory and its research infrastructure, give a brief discussion of the respective research programs and methods, and present recent highlights.
It has previously been demonstrated that the presence of fetal bovine serum is necessary for TGF-β3 (transforming growth factor beta 3)-dependent elimination of low-dose hyper-radiosensitivity (HRS) ...in cells by 1 h of low-dose-rate γ-irradiation (0.2-0.3 Gy/h). The purpose of the present study was to identify the serum constituent involved. Two human HRS-positive (T-47D, T98G) cell lines were used. The effects of different pretreatments on HRS were investigated using the colony assay. Total inducible nitric oxide synthase (iNOS) levels were measured using a cell-based ELISA assay. The serum factor was identified as interleukin-13 (IL-13). In order for low dose-rate irradiation to eliminate HRS through the TGF-β3-dependent mechanism, the cells must be exposed to IL-13 first. Inhibiting receptor IL-13Rα2 showed that this receptor is involved in the response. Adding IL-13 to serum-free medium restored the properties of full medium but not when an inhibitor of proprotein convertase activity was added together with IL-13. The presence of IL-13 resulted in upregulation of total iNOS protein levels. Thus, this study indicates that IL-13 interacts with the cells though receptor IL-13Rα2 and induces upregulation of iNOS and activation of one or more furin-like proprotein convertases.
Purpose: Compare the sensitivity of human cells in vitro to low dose-rate irradiation in air and in moderate hypoxia (4% O2).
Materials and methods: Continuous low dose-rate β-irradiation at a dose ...rate of 0.015 or 0.062 Gy h was given to human T-47D breast cancer cells by incorporation of 3H -labelled valine into cellular protein. Acute irradiation at a dose rate of 0.4 Gy min was performed using 137Csγ-irradiation. Cells were cultivated in an atmosphere with 4% O2 using an INVIVO2 hypoxia cabinet.
Results: When grown in ambient air with continuous irradiation, T-47D cells were able to continue growth for at least 23 weeks at a dose-rate of 0.015 Gy h with a surviving fraction stabilized at around 60%. When the dose rate was increased to 0.062 Gy h the cell culture died out after about 23 days (corresponding to about 22 Gy). When grown in an atmosphere with 4% O2 we surprisingly found that the continuously irradiated T-47D cells (0.015 Gy h) were severely inhibited in their growth, and cell death became extensive after about 3 weeks while un-irradiated cells continued growth seemingly unaffected by this low oxygenation. Peri cellular oxygenation varied between 4% and below 0.1% over an ordinary passage due to diffusion-limitations through the 2 mm deep medium. Online O2-recordings over a whole passage showed that oxygen was more depleted in the irradiated compared to the un-irradiated cultures indicating increased respiration during irradiation. While cells growing attached to the bottom were inhibited and inactivated during irradiation it was found that cells attached high up in the neck region, i.e., having only a shallow layer of medium above them, survived and formed colonies. When cells cultivated in 4% O2 for 7 weeks were irradiated with acute doses of 137Cs γ-rays, the radiosensitivity was the same as for cells cultivated in ambient air.
Conclusion: Continuous irradiation with 0.015 Gy h for several weeks results in a stronger inhibition for T-47D cells grown in an atmosphere with 4% as compared to 20% O2. The data indicate that this may be due to increased oxygen consumption resulting in more severe hypoxia in 3H-incorporating compared to control (un-irradiated) cells.
Accurate representation of subject-specific bone anatomy in lower-limb musculoskeletal models is important for human movement analyses and simulations. Mathematical methods can reconstruct geometric ...bone models using incomplete imaging of bone by morphing bone model templates, but the validity of these methods has not been fully explored. The purpose of this study was to determine the minimal imaging requirements for accurate reconstruction of geometric bone models. Complete geometric pelvis and femur models of 14 healthy adults were reconstructed from magnetic resonance imaging through segmentation. From each complete bone segmentation, three sets of incomplete segmentations (set 1 being the most incomplete) were created to test the effect of imaging incompleteness on reconstruction accuracy. Geometric bone models were reconstructed from complete sets, three incomplete sets, and two motion capture-based methods. Reconstructions from (in)complete sets were generated using statistical shape modelling, followed by host-mesh and local-mesh fitting through the Musculoskeletal Atlas Project Client. Reconstructions from motion capture-based methods used positional data from skin surface markers placed atop anatomic landmarks and estimated joint centre locations as target points for statistical shape modelling and linear scaling. Accuracy was evaluated with distance error (mm) and overlapping volume similarity (%) between complete bone segmentation and reconstructed bone models, and statistically compared using a repeated measure analysis of variance (p<0.05). Motion capture-based methods produced significantly higher distance error than reconstructions from (in)complete sets. Pelvis volume similarity reduced significantly with the level of incompleteness: complete set (92.70±1.92%), set 3 (85.41±1.99%), set 2 (81.22±3.03%), set 1 (62.30±6.17%), motion capture-based statistical shape modelling (41.18±9.54%), and motion capture-based linear scaling (26.80±7.19%). A similar trend was observed for femur volume similarity. Results indicate that imaging two relevant bone regions produces overlapping volume similarity >80% compared to complete segmented bone models, and improve analyses and simulation over current standard practice of linear scaling musculoskeletal models.
Spatially fractionated radiation therapy (SFRT or GRID) is an approach to deliver high local radiation doses in an 'on-off' pattern. To better appraise the radiobiological effects from GRID, a ...framework to link local radiation dose to clonogenic survival needs to be developed. A549 (lung) cancer cells were irradiated in T25 cm\(^2\) flasks using 220 kV X-rays with an open field or through a tungsten GRID collimator with periodical 5 mm openings and 10 mm blockings. Delivered nominal doses were 2, 5, and 10 Gy. A novel approach for image segmentation was used to locate the centroid of surviving colonies in scanned images of the cell flasks. GafchromicTM film dosimetry (GFD) and FLUKA Monte Carlo (MC) simulations were employed to map the dose distribution in the flasks at each surviving colony centroid. Fitting the linear-quadratic (LQ) function to clonogenic survival data for open field irradiation, the expected survival level at a given dose level was calculated. The expected survival level was then mapped together with the observed levels in the GRID-irradiated flasks. GFD and FLUKA MC gave similar dose distributions, with a mean peak-to-valley dose ratio of about 5. LQ-parameters for open field irradiation gave \(\alpha = 0.16 \pm 0.04\) Gy\(^{-1}\) and \(\beta = 0.001 \pm 0.004\) Gy\(^{-2}\). Using the image segmentation method, the mean absolute percentage deviation between observed and predicted survival in the (peak; valley) dose regions was (8; 10) %, (4; 41) %, and (3; 138) % for 2, 5 and 10 Gy, respectively. In conclusion, a framework for mapping of surviving colonies following GRID irradiation together with predicted survival levels from homogeneous irradiation was presented. For the given cell line, our findings indicate that GRID irradiation, especially at high peak doses, causes reduced survival compared to an open field configuration.
Summary Objective To cross-culturally adapt and validate Singapore English and Chinese versions of the Oxford Knee Score (OKS) in patients with knee osteoarthritis (OA) undergoing total knee ...replacement (TKR) surgery. Methods Singapore English and Chinese OKS versions were cross-culturally adapted from the source English version following standard guidelines (including cognitive debriefing), and validated by interviewing patients in English or Chinese using an identical, pretested questionnaire containing the OKS, Short Form 36, and EQ-5D. Reliability was assessed using Cronbach's α , dimensionality using principal component factor analysis and item-total correlations, convergent and divergent construct validity by assessing six and three a priori hypotheses, respectively. Results The Singapore English and Chinese OKS were well accepted by patients in pilot testing. When administered to a consecutive sample of 127 English and 131 Chinese-speaking Singaporeans with knee OA (mean age 66 years, 83% female, mean duration of OA 6 years, Chinese:Malay:Indian:Others = 78:7.9:11:3.1% for English version), Cronbach's α exceeded 0.8 and factor analysis yielded three factors for both versions. Hypothesized item-total correlations (Spearman's ρ ≥ 0.4) were observed for all items except limping, kneeling, and night knee pain in both versions. Convergent construct validity was supported by the presence of hypothesized moderate/strong correlations ( ρ = 0.37–0.73) for six and five a priori hypotheses in English and Chinese versions, respectively. Divergent construct validity was supported by the presence of weak correlations ( ρ = 0.09–0.30) for all three a priori hypotheses in both versions. Conclusion Singapore English and Chinese OKS demonstrated good patient acceptability and psychometric properties (including construct validity) among multiethnic Asian patients with knee OA undergoing TKR.
Background
The role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk ...stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment.
Method
Patients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10 years were included at 21 emergency surgical centres and from age 5 years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score‐based algorithm was implemented during the intervention period. Intermediate‐risk patients were randomized to routine imaging or selective imaging after clinical reassessment.
Results
The baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate‐risk patients were randomized. In low‐risk patients, use of the AIR score‐based algorithm resulted in less imaging (19·2 versus 34·5 per cent; P < 0·001), fewer admissions (29·5 versus 42·8 per cent; P < 0·001), and fewer negative explorations (1·6 versus 3·2 per cent; P = 0·030) and operations for non‐perforated appendicitis (6·8 versus 9·7 per cent; P = 0·034). Intermediate‐risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (6·4 versus 6·7 per cent respectively; P = 0·884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4 versus 46·3 per cent; P = 0·020).
Conclusion
AIR score‐based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 (
http://www.clinicaltrials.gov).
Reduces imaging and admissions
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