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  • Brunnström, Kjell, et al. (author)
  • 3D Video Quality of Experience - Influence of Scale and Crosstalk Invited
  • 2014
  • In: Proceedings of the 8th International Workshop on Video Processing and Quality Metrics for Consumer Electronics VPQM-2014. - Scottsdale, AZ, USA.
  • Conference paper (peer-reviewed)abstract
    • This paper gives an overview of three recent studies by the authors on the topic of 3D video Quality of Experience (QoE). Two of studies [1,2] investigated different psychological dimension that may be needed for describing 3D video QoE and the third the visibility and annoyance of crosstalk[3]. The results shows that the video quality scale could be sufficient for evaluating S3D video experience for coding and spatial resolution reduction distortions. It was also confirmed that with a more complex mixture of degradations more than one scale should be used to capture the QoE in these cases. The study found a linear relationship between the perceived crosstalk and the amount of crosstalk.
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  • den Dulk, M., et al. (author)
  • Multicentre analysis of oncological and survival outcomes following anastomotic leakage after rectal cancer surgery
  • 2009
  • In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 96:9, s. 1066-75
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The association between diverting stomas and symptomatic anastomotic leakage after rectal cancer surgery was studied, as well as the impact of leakage on local recurrence, distant metastasis, and disease-free, overall and cancer-specific survival. METHODS: Data from the Swedish Rectal Cancer Trial, Dutch TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial were pooled (n = 5187). All eligible patients without distant metastases at the time of low anterior resection were selected (n = 2726); overall survival was studied in patients aged 75 years or less (n = 2480). Multivariable models were used to study the association between diverting stomas and anastomotic leakage, and between leakage and recurrence or survival. RESULTS: Some 9.7 per cent of patients were diagnosed with a symptomatic anastomotic leak; diverting stomas were negatively associated with leakage (11.6 per cent without and 7.8 per cent with a stoma; P = 0.002). Anastomotic leakage was negatively associated with overall survival in the multivariable analysis (hazard ratio (HR) 1.29 (95 per cent confidence interval 1.02 to 1.63); P = 0.034), but not with cancer-specific survival (HR 1.12 (0.83 to 1.52); P = 0.466). CONCLUSION: Diverting stomas were associated with less symptomatic anastomotic leakage. Oncological outcome was not significantly influenced by leakage, but overall survival was reduced.
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  • Folkesson, E., et al. (author)
  • Proteomic comparison of osteoarthritic and reference human menisci using data-independent acquisition mass spectrometry
  • 2020
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:8, s. 1092-1101
  • Journal article (peer-reviewed)abstract
    • Objective: Recent research in knee osteoarthritis (OA) highlights the role of the meniscus in OA pathology. Our aim was to compare the proteomes of medial and lateral menisci from end-stage medial compartment knee OA patients, with reference menisci from knee-healthy deceased donors, using mass spectrometry. Design: Tissue plugs of Ø3 mm were obtained from the posterior horns of the lateral and medial menisci from one knee of 10 knee-healthy deceased donors and 10 patients undergoing knee replacement. Proteins were extracted and prepared for mass spectrometric analysis. Statistical analysis was conducted on abundance data that was log2-transformed, using a linear mixed effects model and evaluated using pathway analysis. Results: We identified a total of 835 proteins in all samples, of which 331 were included in the statistical analysis. The largest differences could be seen between the medial menisci from OA patients and references, with most proteins showing higher intensities in the medial menisci from OA patients. Several matrix proteins, e.g., matrix metalloproteinase 3 (MMP3) (4.3 times higher values [95%CI 1.8, 10.6]), TIMP1 (3.5 [1.4, 8.5]), asporin (4.1 [1.7, 10.0]) and versican (4.4 [1.8, 10.9]), all showed higher abundance in medial menisci from OA patients compared to medial reference menisci. OA medial menisci also showed increased activation of several pathways involved in inflammation. Conclusion: An increase in protein abundance for proteins such as MMP and TIMP1 in the medial menisci from OA patients suggests simultaneous activation of both catabolic and anabolic processes that warrants further attention.
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  • Folkesson, M., et al. (author)
  • Proteolytically active ADAM10 and ADAM17 carried on membrane microvesicles in human abdominal aortic aneurysms
  • 2015
  • In: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 114:6, s. 1165-1174
  • Journal article (peer-reviewed)abstract
    • The intraluminal thrombus (ILT) of human abdominal aortic aneurysm (AAA) has been suggested to damage the underlying aortic wall, but previous work found scant activity of soluble proteases in the abluminal layer of the ILT, adjacent to the aneurysm. We hypothesised that transmembrane proteases carried by membrane microvesicles (MV) from dying cells remain active in the abluminal ILT. ILTs and AAA segments collected from 21 patients during surgical repair were assayed for two major transmembrane proteases, ADAM10 (a disintegrin and metalloprotease-10) and ADAM17. We also exposed cultured cells to tobacco smoke and assessed ADAM10 and ADAM17 expression and release on MVs. Immunohistochemistry showed abundant ADAM10 and ADAM17 protein in the ILT and underlying aneurysmal aorta. Domain-specific antibodies indicated both transmembrane and shed ADAM17. Importantly, ADAM10 and ADAM 17 in the abluminal ILT were enzymatically active. Electron microscopy of abluminal ILT and aortic wall showed MVs with ADAM10 and ADAM17. By flow cytometry, ADAM-positive microvesicles from abluminal ILT carried the neutrophil marker CD66, but not the platelet marker CD61. Cultured HL60 neutrophils exposed to tobacco smoke extract showed increased ADAM10 and ADAM17 content, cleavage of these molecules into active forms, and release of MVs carrying mature ADAM10 and detectable ADAM17. In conclusion, our results implicate persistent, enzymatically active ADAMs on MVs in the abluminal ILT, adjacent to the aneurysmal wall. The production of ADAM10- and ADAM17-positive MVs from smoke-exposed neutrophils provides a novel molecular mechanism for the vastly accelerated risk of AAA in smokers.
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  • Gasser, T. Christian, et al. (author)
  • Micromechanical Characterization of Intra-luminal Thrombus Tissue from Abdominal Aortic Aneurysms
  • 2010
  • In: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 38:2, s. 371-379
  • Journal article (peer-reviewed)abstract
    • The reliable assessment of Abdominal Aortic Aneurysm rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. Intra-luminal thrombus (ILT) has multiple biomechanical and biochemical impacts on the underlying aneurysm wall and thrombus failure might be linked to aneurysm rupture. Histological slices from 7 ILTs were analyzed using a sequence of automatic image processing and feature analyzing steps. Derived microstructural data was used to define Representative Volume Elements (RVE), which in turn allowed the estimation of microscopic material properties using the non-linear Finite Element Method. ILT tissue exhibited complex microstructural arrangement with larger pores in the abluminal layer than in the luminal layer. The microstructure was isotropic in the abluminal layer, whereas pores started to orient along the circumferential direction towards the luminal site. ILT's macroscopic (reversible) deformability was supported by large pores in the microstructure and the inhomogeneous structure explains in part the radially changing macroscopic constitutive properties of ILT. Its microscopic properties decreased just slightly from the luminal to the abluminal layer. The present study provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture. Data provided in this study allow an integration of structural information from medical imaging for example, to estimate ILT's macroscopic mechanical properties.
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  • Karjalainen, V. P., et al. (author)
  • Quantitative three-dimensional collagen orientation analysis of human meniscus posterior horn in health and osteoarthritis using micro-computed tomography
  • 2021
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:5, s. 762-772
  • Journal article (peer-reviewed)abstract
    • Objective: Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (μCT), and to compare the local microstructural organization between OA and donor samples. Method: We collected posterior horns of both medial and lateral human menisci from 10 end-stage medial compartment knee OA patients undergoing total knee replacement (medial & lateral OA) and 10 deceased donors without knee OA (medial & lateral donor). Posterior horns were dissected and fixed in formalin, dehydrated in ascending ethanol concentrations, treated with hexamethyldisilazane (HMDS), and imaged with μCT. We performed local orientation analysis of collagenous microstructure in 3D by calculating structure tensors from greyscale gradients within selected integration window to determine the polar angle for each voxel. Results: In donor samples, meniscus bundles were aligned circumferentially around the inner border of meniscus. In medial OA menisci, the organized structure of collagen network was lost, and main orientation was shifted away from the circumferential alignment. Quantitatively, medial OA menisci had the lowest mean orientation angle compared to all groups, −24° (95%CI -31 to −18) vs medial donor and −25° (95%CI -34 to −15) vs lateral OA. Conclusions: HMDS-based μCT imaging enabled quantitative analysis of meniscal collagen fiber bundles and their orientations in 3D. In human medial OA menisci, the collagen disorganization was profound with overall lower orientation angles, suggesting collagenous microstructure disorganization as an important part of meniscus degradation.
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  • Kestilä, I., et al. (author)
  • Three-dimensional microstructure of human meniscus posterior horn in health and osteoarthritis
  • 2019
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:22, s. 1790-1799
  • Journal article (peer-reviewed)abstract
    • Objective: To develop and perform ex vivo 3D imaging of meniscus posterior horn microstructure using micro-computed tomography (μCT), and to compare specimens from healthy references against end-stage osteoarthritis (OA) using conventional section-based histology and qualitative μCT. Design: We retrieved human medial and lateral menisci from 10 deceased donors without knee OA (healthy references) and medial and lateral menisci from 10 patients having total knee replacement for medial compartment OA. Meniscal posterior horns were dissected and fixed in formalin. One subsection underwent hexamethyldisilazane (HMDS) treatment and μCT imaging. Pauli's histopathological scoring was performed for 3 other subsections. The differences in histopathological scores were estimated using mixed linear regression, resulting in fixed effects estimates for within-knee comparisons and adjusted for age and body mass index for between-subjects comparisons. Results: 3D visualization with μCT qualitatively revealed similar microstructural changes in the posterior horns as conventional histology. The mean histopathological score was higher for medial menisci from OA knees vs both medial reference menisci (mean difference [95% CI], 3.9 [2.6,5.3]), and lateral menisci from OA knees (3.9 [2.9,5.0]). The scores were similar between lateral menisci from OA knees and lateral reference menisci (0.8 [−0.6,2.2]), and between medial and lateral reference menisci (0.8 [−0.3,1.9]). Conclusions: HMDS-based μCT protocol allows unique 3D visualization of meniscus microstructures. Posterior horns of medial menisci from medial compartment OA knees had higher histopathological scores than both the lateral posterior horns from the same OA knees and medial reference menisci, suggesting a strong association between meniscus degradation and unicompartmental knee OA.
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  • Thippur, Akshaya, et al. (author)
  • KTH-3D-TOTAL : A 3D dataset for discovering spatial structures for long-term autonomous learning
  • 2014
  • In: 2014 13th International Conference on Control Automation Robotics and Vision, ICARCV 2014. - : IEEE. - 9781479951994 ; , s. 1528-1535
  • Conference paper (peer-reviewed)abstract
    • Long-term autonomous learning of human environments entails modelling and generalizing over distinct variations in: object instances in different scenes, and different scenes with respect to space and time. It is crucial for the robot to recognize the structure and context in spatial arrangements and exploit these to learn models which capture the essence of these distinct variations. Table-tops posses a typical structure repeatedly seen in human environments and are identified by characteristics of being personal spaces of diverse functionalities and dynamically changing due to human interactions. In this paper, we present a 3D dataset of 20 office table-tops manually observed and scanned 3 times a day as regularly as possible over 19 days (461 scenes) and subsequently, manually annotated with 18 different object classes, including multiple instances. We analyse the dataset to discover spatial structures and patterns in their variations. The dataset can, for example, be used to study the spatial relations between objects and long-term environment models for applications such as activity recognition, context and functionality estimation and anomaly detection.
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  • Augustsson, Jesper, 1964, et al. (author)
  • Single-leg hop testing following fatiguing exercise: reliability and biomechanical analysis
  • 2006
  • In: Scand J Med Sci Sports. - : Wiley. - 0905-7188. ; 16:2, s. 111-20
  • Journal article (peer-reviewed)abstract
    • A fatiguing exercise protocol was combined with single-leg hop testing to improve the possibilities of evaluating the effects of training or rehabilitation interventions. In the first test-retest experiment, 11 healthy male subjects performed two trials of single-leg hops under three different test conditions: non-fatigued and following fatiguing exercise, which consisted of unilateral weight machine knee extensions at 80% and 50%, respectively, of 1 repetition maximum (1 RM) strength. Intraclass correlation coefficients ranged from 0.75 to 0.98 for different hop test conditions, indicating that all tests were reliable. For the second experiment, eight healthy male subjects performed the fatiguing exercise protocol to investigate how fatigue influences lower-extremity joint kinematics and kinetics during single-leg hops. Hip, knee and ankle joint angles, moments and powers, as well as ground-reaction forces were recorded with a six-camera, motion-capture system and a force platform. Recovery of hop performance following the fatiguing exercise was also measured. During the take-off for the single-leg hops, hip and knee flexion angles, generated powers for the knee and ankle joints, and ground-reaction forces decreased for the fatigued hop conditions compared with the non-fatigued condition (P<0.05). Compared with landing during the non-fatigued condition, hip moments and ground-reaction forces were lower for the fatigued hop conditions (P<0.05). The negative joint power was two to three times greater for the knee than for the hip and five to 10 times greater for the knee than for the ankle during landing for all test conditions (P<0.05). Most measured variables had recovered three minutes post-exercise. It is concluded that the fatiguing exercise protocol combined with single-leg hop testing was a reliable method for investigating functional performance under fatigued test conditions. Further, subjects utilized an adapted hop strategy, which employed less hip and knee flexion and generated powers for the knee and ankle joints during take-off, and less hip joint moments during landing under fatigued conditions. The large negative power values observed at the knee joint during the landing phase of the single-leg hop, during which the quadriceps muscle activates eccentrically, indicate that not only hop distance but also the ability to perform successful landings should be investigated when assessing dynamic knee function.
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  • den Dulk, Marcel, et al. (author)
  • The abdominoperineal resection itself is associated with an adverse outcome : The European experience based on a pooled analysis of five European randomised clinical trials on rectal cancer
  • 2009
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:7, s. 1175-1183
  • Journal article (peer-reviewed)abstract
    • PURPOSE: The aim of this study is to identify factors associated with the decision to perform an abdominoperineal resection (APR) and to assess if these factors or the surgical procedure itself is associated with circumferential resection margin (CRM) involvement, local recurrence (LR), overall survival (OS) and cancer-specific survival (CSS). PATIENTS AND METHODS: The Swedish Rectal Cancer Trial (SRCT), TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial (PRCT) were pooled. A propensity score was calculated, which indicated the predicted probability of undergoing an APR given gender, age and distance, and used in the multivariate analyses. RESULTS: An APR procedure was associated with an increased risk of CRM involvement [odd ratio (OR) 2.52, p<0.001], increased LR rate [hazard ratio (HR) 1.53, p=0.001] and decreased CSS rate (HR 1.31, p=0.002), whereas the propensity score was not. CONCLUSION: The results suggest that the APR procedure itself is a significant predictor for non-radical resections and increased risk of LR and death due to cancer for patients with advanced rectal cancer.
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  • Eriksson, Leif, 1970, et al. (author)
  • ALOS PALSAR Calibration and Validation Results from Sweden
  • 2007
  • In: IEEE Geoscience and Remote Sensing Symposium (IGARSS 2007), Barcelona, Spain, July 23-27, 2007. ; DOI: 10.1109/IGARSS.2007.4423115, s. 1589-1592
  • Conference paper (other academic/artistic)abstract
    • In 2006 calibration activities for ALOS PALSAR wereconducted in Sweden. Four five-metre trihedral corner reflectorsand three smaller dihedral reflectors were deployed and operatedduring eight months. 23 PALSAR scenes were acquired over thecalibration site allowing an evaluation of the quality and temporalstability of the data. Results show that the co-polarized datahave been stable during the whole calibration period with variationsin the trihedral responses lower than 0.7 dB. The measuredresolution in azimuth was 4.4 m and in slant range 4.7 m forsingle polarization images and 9.5 m for polarimetric data. Forthe cross-polarized data large variations in the dihedral responseswere found. It is assumed that this is caused by a larger sensitivityto pointing errors. For the polarimetric data, estimation ofFaraday rotation gave values ranging from 0.1º to 3º.
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  • Folkesson, Mattias, 1972-, et al. (author)
  • Immunohistochemical changes in the expression of HSP27 in exercised human vastus lateralis muscle
  • 2008
  • In: Acta Physiologica. - : Blackwell Publishing. - 1748-1708 .- 1748-1716. ; 194:3, s. 215-222
  • Journal article (peer-reviewed)abstract
    • Aim: The role of HSP27 in the adaptive process of skeletal muscle to exercise, especially in humans, is not well understood. The objective of this study was to investigate immunohistochemical changes in HSP27 expression in human vastus lateralis muscle following resistance and endurance exercises.Methods: Two different exercise protocols were used: (1) one-leg ergometer cycling (EC, n = 6) consisting of two 30-min bouts at 40% and 75% of peak oxygen uptake, respectively, and (2) leg extension resistance exercise (RE, n = 9) including 10 sets of eight repetitions at a load corresponding to 70% of one maximal repetition (1RM). Immunohistochemistry using specific monoclonal antibodies was used to determine the location of HSP27 protein in muscle biopsies from human vastus lateralis.Results: Our results show that RE, but not EC, induced a significant appearance of scattered accumulations of HSP27 protein in muscle fibres from five of nine subjects. The number of fibres with accumulation of HSP27 in RE ranged from 0% to 32% with a mean of 6.3% of the total number of fibres.Conclusion: We conclude that this rapid HSP27 protein relocation after RE is an important player in the cellular remodelling of human muscle fibres in response to exercise involving high-force contractions, but not in response to endurance exercises.
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  • Fransson, J.E.S., et al. (author)
  • Mapping of Wind-Thrown Forests Using VHF/UHF SAR Images
  • 2007
  • In: IEEE 2007 International Geoscience and Remote Sensing Symposium (IGARSS 2007), Barcelona, Spain, July 23-27 2007. ; DOI: 10.1109/IGARSS.2007.4423313, s. 2350-2353
  • Conference paper (other academic/artistic)abstract
    • SAR images from the Swedish airborne CARABAS-II and LORA systems have been visually analyzed over simulated wind-thrown forest at both single tree and stand level. In ideal conditions, the results show that LORA is more accurate than CARABAS-II at detecting wind-thrown trees, regardless of tree size and direction of the fallen trees relative to flight heading. Furthermore, the visible single trees in the LORA images appeared more distinct than in the CARABAS-II images, which could be explained by the high resolution in the LORA images. Based on visual interpretation, it is likely that the detection of wind-thrown forests could be improved using VHF/UHF SAR images acquired both prior to and after a storm event.
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  • Gasser, T. Christian, et al. (author)
  • Failure properties of intraluminal thrombus in abdominal aortic aneurysm under static and pulsating mechanical loads
  • 2008
  • In: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 48:1, s. 179-188
  • Journal article (peer-reviewed)abstract
    • Objectives: It has been suggested that mechanical failure of intraluminal thrombus (ILT) could play a key role in the rupture of abdominal aortic aneurysms (AAAs), and in the present study, this hypothesis has been investigated. An in vitro experimental approach has been proposed, which provides layer-specific failure data of ILT tissue under static and pulsatile mechanical loads. Methods. In total, 112 bone-shaped test specimens are prepared from luminal, medial, and abluminal layers of eight ILTs harvested during open elective AAA repair. Three different types of mechanical experiments, denoted as control test, ultimate strength test, and fatigue test were performed in Dulbecco's modified eagle's medium (DMEM) supplemented with fetal calf serum, L-ascorbic acid, and antibiotics at 37 degrees C and pH 7.0. In detail, fatigue tests, which are experiments, where the ILT tissue is loaded. in pulsatile manner, were carried out at three different load levels with a natural frequency of 1.0 Hz. Results. ILT's ultimate strength (156.5 kPa, 92.0 kPa, and 47.7 kPa for luminal, medial, and abluminal layers, respectively) and referential stiffness (62.88 kPa, 47.52 kPa, and 41.52 kPa, for luminal, medial, and abluminal layers, respectively) continuously decrease from the inside to the outside. ILT tissue failed within less than 1 hour under pulsatile loading at a load level of 60% ultimate strength, while a load level of about 40% ultimate strength did not cause failure within 13.9 hours. Conclusions. ILT tissue is vulnerable against fatigue failure and shows significant decreasing strength with respect to the number of load cycles. Hence, after a reasonable time of pulsating loading ILT's strength is far below its ultimate strength, and when compared with stress predictions from finite element (FE) studies, this indicates the likelihood of fatigue failure in vivo. Failure within the ILT could propagate towards the weakened vessel wall behind it and could initialize AAA failure thereafter.
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  • Kurbasic, Emila, et al. (author)
  • Changes in glycoprotein expression between primary breast tumour and synchronous lymph node metastases or asynchronous distant metastases.
  • 2015
  • In: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1559-0275 .- 1542-6416. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Breast cancer is a very heterogeneous disease and some patients are cured by the surgical removal of the primary tumour whilst other patients suffer from metastasis and spreading of the disease, despite adjuvant therapy. A number of prognostic and treatment predictive factors have been identified such as tumour size, oestrogen (ER) and progesterone (PgR) receptor status, human epidermal growth factor receptor type 2 (HER2) status, histological grade, Ki67 and age. Lymph node involvement is also assessed during surgery to determine if the tumour has spread which requires dissection of the axilla and adjuvant treatment. The prognostic and treatment predictive factors assessing the nature of the tumour are all routinely based on the status of the primary tumour.
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  • Olsson, E., et al. (author)
  • Ultra-high field magnetic resonance imaging parameter mapping in the posterior horn of ex vivo human menisci
  • 2019
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:3, s. 476-483
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). Design: We sampled medial and lateral menisci from ten medial compartment knee OA patients (mean age 63 years) undergoing total knee replacement and from ten deceased donors (references, mean age 51 years). MR relaxation parameters T2*, T2 and T1 of the posterior horn were measured at a 9.4 T scanner. Comparisons were made between OA patients and references (with adjustment for age) as well as between medial and lateral menisci from the same knees. Results: Mean values (standard deviation) of mean T2* were 13 (3.8), 6.9 (2.3), 7.2 (1.9) and 7.2 (1.7) ms for the medial and lateral patient menisci and the medial and lateral reference menisci, respectively. Corresponding values were 17 (3.7), 9.0 (2.2), 12 (4) and 9.0 (1.3) ms for T2 and 1810 (150), 1630 (30), 1580 (90) and 1560 (50) ms for T1. All three relaxation times were significantly longer in medial OA menisci compared to the other groups. Among medial reference menisci, relaxation times (mainly T1) tended to increase with age. Conclusions: MR relaxation times T2*, T2 and T1 in the posterior horn are longer in the medial menisci of patients with end-stage medial compartment knee OA compared to the corresponding lateral menisci and to reference menisci. The meniscus seems to undergo intrasubstance alterations related to both OA and ageing.
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  • Silva, CS, et al. (author)
  • High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
  • 2021
  • In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 727300-
  • Journal article (peer-reviewed)abstract
    • Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
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