| 1. |
- Aasvang, Gunn Marit, et al.
(författare)
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Burden of disease due to transportation noise in the Nordic countries.
- 2023
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Ingår i: Environmental research. - 1096-0953. ; 231:Pt 1
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Tidskriftsartikel (refereegranskat)abstract
- Environmental noise is of increasing concern for public health. Quantification of associated health impacts is important for regulation and preventive strategies.To estimate the burden of disease (BoD) due to road traffic and railway noise in four Nordic countries and their capitals, in terms of DALYs (Disability-Adjusted Life Years), using comparable input data across countries.Road traffic and railway noise exposure was obtained from the noise mapping conducted according to the Environmental Noise Directive (END) as well as nationwide noise exposure assessments for Denmark and Norway. Noise annoyance, sleep disturbance and ischaemic heart disease were included as the main health outcomes, using exposure-response functions from the WHO, 2018 systematic reviews. Additional analyses included stroke and type 2 diabetes. Country-specific DALY rates from the Global Burden of Disease (GBD) study were used as health input data.Comparable exposure data were not available on a national level for the Nordic countries, only for capital cities. The DALY rates for the capitals ranged from 329 to 485 DALYs/100,000 for road traffic noise and 44 to 146 DALY/100,000 for railway noise. Moreover, the DALY estimates for road traffic noise increased with up to 17% upon inclusion of stroke and diabetes. DALY estimates based on nationwide noise data were 51 and 133% higher than the END-based estimates, for Norway and Denmark, respectively.Further harmonization of noise exposure data is required for between-country comparisons. Moreover, nationwide noise models indicate that DALY estimates based on END considerably underestimate national BoD due to transportation noise. The health-related burden of traffic noise was comparable to that of air pollution, an established risk factor for disease in the GBD framework. Inclusion of environmental noise as a risk factor in the GBD is strongly encouraged.
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| 2. |
- Akhi, Ramin, et al.
(författare)
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Cross-reactive saliva IgA antibodies to oxidized LDL and periodontal pathogens in humans.
- 2017
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 44:7, s. 682-691
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and are highly immunogenic and proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were characterized and their cross-reactivity was evaluated.MATERIALS AND METHODS: Resting and stimulated saliva samples were collected from 36 healthy adults (mean age 26 years). Saliva IgA, IgG and IgM autoantibody levels to copper oxidized LDL (CuOx-LDL) and malondialdehyde acetaldehyde-modified LDL (MAA-LDL) were determined with chemiluminescence immunoassay.RESULTS: Saliva IgA and IgG antibodies binding to MAA-LDL and CuOx-LDL were detected in all samples and they were associated with the saliva levels of IgA and IgG to P. gingivalis and A. actinomycetemcomitans. Competitive immunoassay showed that saliva antibodies to MAA-LDL cross-reacted specifically with P. gingivalis. The autoantibody levels to oxLDL in saliva were not associated with the autoantibody levels to oxLDL in plasma or with saliva apolipoprotein B 100 levels.CONCLUSIONS: Saliva contains IgA and IgG binding to oxLDL, which showed cross-reactive properties with the periodontal pathogens Porphyromonas gingivalis (P.g). The data suggest that secretory IgA to P.g may participate in immune reactions involved in LDL oxidation through molecular mimicry.
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| 3. |
- Døvling Kaspersen, Jørn, et al.
(författare)
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Small-Angle X-ray Scattering Demonstrates Similar Nanostructure in Cortical Bone from Young Adult Animals of Different Species.
- 2016
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X.
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Tidskriftsartikel (refereegranskat)abstract
- Despite the vast amount of studies focusing on bone nanostructure that have been performed for several decades, doubts regarding the detailed structure of the constituting hydroxyapatite crystal still exist. Different experimental techniques report somewhat different sizes and locations, possibly due to different requirements for the sample preparation. In this study, small- and wide-angle X-ray scattering is used to investigate the nanostructure of femur samples from young adult ovine, bovine, porcine, and murine cortical bone, including three different orthogonal directions relative to the long axis of the bone. The radially averaged scattering from all samples reveals a remarkable similarity in the entire q range, which indicates that the nanostructure is essentially the same in all species. Small differences in the data from different directions confirm that the crystals are elongated in the [001] direction and that this direction is parallel to the long axis of the bone. A model consisting of thin plates is successfully employed to describe the scattering and extract the plate thicknesses, which are found to be in the range of 20-40 Å for most samples but 40-60 Å for the cow samples. It is demonstrated that the mineral plates have a large degree of polydispersity in plate thickness. Additionally, and equally importantly, the scattering data and the model are critically evaluated in terms of model uncertainties and overall information content.
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| 4. |
- Finnilä, Mikko A J, et al.
(författare)
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Mineral Crystal Thickness in Calcified Cartilage and Subchondral Bone in Healthy and Osteoarthritic Human Knees
- 2022
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 37:9, s. 1700-1710
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage.
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| 5. |
- Forsman, Ulrika, et al.
(författare)
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4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures
- 2010
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Ingår i: Nature chemical biology. - 1552-4450 .- 1552-4469. ; 6:7, s. 515-517
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Tidskriftsartikel (refereegranskat)abstract
- Coenzyme Q (Q) is an electron transporter in the respiratory chain and a lipid-soluble antioxidant that decreases in humans with age. Here we show that 4-nitrobenzoate inhibited 4-hydroxybenzoate: polyprenyl transferase (Coq2) in a competitive manner and dose-dependently decreased Q in mammalian cells without accumulation of Q intermediates. As 4-nitrobenzoate neither interfered with mitochondrial respiration nor induced oxidative stress, it should prove a valuable tool for studies on both Q deficiency and Q supplementation.
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| 6. |
- Gustafsson, Anna, et al.
(författare)
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Linking multiscale deformation to microstructure in cortical bone using in situ loading, digital image correlation and synchrotron X-ray scattering
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 69, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of fragility fractures is expected to increase in the near future due to an aging population. Therefore, improved tools for fracture prediction are required to treat and prevent these injuries efficiently. For such tools to succeed, a better understanding of the deformation mechanisms in bone over different length scales is needed. In this study, an experimental setup including mechanical tensile testing in combination with digital image correlation (DIC) and small/wide angle X-ray scattering (SAXS/WAXS) was used to study deformation at multiple length scales in bovine cortical bone. Furthermore, micro-CT imaging provided detailed information about tissue microstructure. The combination of these techniques enabled measurements of local deformations at the tissue- and nanoscales. The orientation of the microstructure relative to the tensile loading was found to influence the strain magnitude on all length scales. Strains in the collagen fibers were 2-3 times as high as the strains found in the mineral crystals for samples with microstructure oriented parallel to the loading. The local tissue strain at fracture was found to be around 0.5%, independent of tissue orientation. However, the maximum force and the irregularity of the crack path were higher when the load was applied parallel to the tissue orientation. This study clearly shows the potential of combining these different experimental techniques concurrently with mechanical testing to gain a better understanding of bone damage and fracture over multiple length scales in cortical bone. Statement of Significance: To understand the pathophysiology of bone, it is important to improve our knowledge about the deformation and fracture mechanisms in bone. In this study, we combine several recently available experimental techniques with mechanical loading to investigate the deformation mechanisms in compact bone tissue on several length scales simultaneously. The experimental setup included mechanical tensile testing in combination with digital image correlation, microCT imaging, and small/wide angle X-ray scattering.The combination of techniques enabled measurements of local deformations at the tissue- and nanoscales. The study clearly shows the potential of combining different experimental techniques concurrently with mechanical testing to gain a better understanding of structure-property-function relationships in bone tissue.
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| 7. |
- Honkanen, Juuso, et al.
(författare)
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Cationic contrast agent diffusion differs between cartilage and meniscus
- 2016
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Ingår i: Annals of Biomedical Engineering. - : Springer. - 0090-6964 .- 1573-9686. ; 44:10, s. 2913-2921
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Tidskriftsartikel (refereegranskat)abstract
- Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.
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| 8. |
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| 9. |
- Isaksson, Hanna, et al.
(författare)
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Neutron tomographic imaging of bone-implant interface : Comparison with X-ray tomography
- 2017
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 103, s. 295-301
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Tidskriftsartikel (refereegranskat)abstract
- Metal implants, in e.g. joint replacements, are generally considered to be a success. As mechanical stability is important for the longevity of a prosthesis, the biological reaction of the bone to the mechanical loading conditions after implantation and during remodelling determines its fate. The bone reaction at the implant interface can be studied using high-resolution imaging. However, commonly used X-ray imaging suffers from image artefacts in the close proximity of metal implants, which limit the possibility to closely examine the bone at the bone-implant interface. An alternative ex vivo 3D imaging method is offered by neutron tomography. Neutrons interact with matter differently than X-rays; therefore, this study explores if neutron tomography may be used to enrich studies on bone-implant interfaces. A stainless steel screw was implanted in a rat tibia and left to integrate for 6 weeks. After extracting the tibia, the bone-screw construct was imaged using X-ray and neutron tomography at different resolutions. Artefacts were visible in all X-ray images in the close proximity of the implant, which limited the ability to accurately quantify the bone around the implant. In contrast, neutron images were free of metal artefacts, enabling full analysis of the bone-implant interface. Trabecular structural bone parameters were quantified in the metaphyseal bone away from the implant using all imaging modalities. The structural bone parameters were similar for all images except for the lowest resolution neutron images. This study presents the first proof-of-concept that neutron tomographic imaging can be used for ex-vivo evaluation of bone microstructure and that it constitutes a viable, new tool to study the bone-implant interface tissue remodelling.
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| 10. |
- Khayyeri, Hanifeh, et al.
(författare)
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Achilles tendon compositional and structural properties are altered after unloading by botox
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Tendon function and homeostasis rely on external loading. This study investigates the biological mechanisms behind tendon biomechanical function and how the mechanical performance is affected by reduced daily loading. The Achilles tendons of 16 weeks old female Sprague Dawley rats (n = 40) were unloaded for 5 weeks by inducing muscle paralysis with botulinum toxin injections in the right gastrocnemius and soleus muscles. The contralateral side was used as control. After harvest, the tendons underwent biomechanical testing to assess viscoelasticity (n = 30 rats) and small angle X-ray scattering to determine the structural properties of the collagen fibrils (n = 10 rats). Fourier transform infrared spectroscopy and histological staining (n = 10 rats) were performed to investigate the collagen and proteoglycan content. The results show that the stiffness increased in unloaded tendons, together with an increased collagen content. Creep and axial alignment of the collagen fibers were reduced. Stress-relaxation increased whereas hysteresis was reduced in response to unloading with botox treatment. Our findings indicate that altered matrix deposition relies on mechanical loading to reorganize the newly formed tissue, without which the viscoelastic behavior is impaired. The results demonstrate that reduced daily loading deprives tendons of their viscoelastic properties, which could increase the risk of injury.
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| 11. |
- Khayyeri, Hanifeh, et al.
(författare)
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Diminishing effects of mechanical loading over time during rat Achilles tendon healing
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12 December
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical loading affects tendon healing and recovery. However, our understanding about how physical loading affects recovery of viscoelastic functions, collagen production and tissue organisation is limited. The objective of this study was to investigate how different magnitudes of loading affects biomechanical and collagen properties of healing Achilles tendons over time. Achilles tendon from female Sprague Dawley rats were cut transversely and divided into two groups; normal loading (control) and reduced loading by Botox (unloading). The rats were sacrificed at 1, 2- and 4-weeks post-injury and mechanical testing (creep test and load to failure), small angle x-ray scattering (SAXS) and histological analysis were performed. The effect of unloading was primarily seen at the early time points, with inferior mechanical and collagen properties (SAXS), and reduced histological maturation of the tissue in unloaded compared to loaded tendons. However, by 4 weeks no differences remained. SAXS and histology revealed heterogeneous tissue maturation with more mature tissue at the peripheral region compared to the center of the callus. Thus, mechanical loading advances Achilles tendon biomechanical and collagen properties earlier compared to unloaded tendons, and the spatial variation in tissue maturation and collagen organization across the callus suggests important regional (mechano-) biological activities that require more investigation.
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| 12. |
- Kyrklund, Mikael, et al.
(författare)
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Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein.
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression of atherosclerosis. We aimed to investigate whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL) and how it would affect the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share cross-reactive epitopes that prompt IgM antibody production and consequently confer atheroprotection. A significant negative association was observed between atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice, supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA levels to Rgp44 and to Pg in both Rgp44- and Pg-immunized mice were significantly higher than those in saline control, suggesting that IgA to Rgp44 could be a surrogate marker of immunization in Pg-immunized mice. Distinct antibody responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS), and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations, indicating that different immunogenic components between Rpg44 and Pg may behave differently in regard of their roles in the development of atherosclerosis. Immunization with Rgp44 also displayed atheroprotective features in modulation of plaque size through association with plasma levels of IL-1α whereas whole Pg bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5 and IL-10. The present study may contribute to refining therapeutic approaches aiming to modulate immune responses and inflammatory/anti-inflammatory processes in atherosclerosis.
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| 13. |
- Le Cann, Sophie, et al.
(författare)
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Investigating the mechanical characteristics of bone-metal implant interface using in situ synchrotron tomographic imaging
- 2019
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 6:JAN
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Tidskriftsartikel (refereegranskat)abstract
- Long-term stability of endosseous implants depends on successful bone formation, ingrowth and adaptation to the implant. Specifically, it will define the mechanical properties of the newly formed bone-implant interface. 3D imaging during mechanical loading tests (in situ loading) can improve the understanding of the local processes leading to bone damage and failure. In this study, titanium screws were implanted into rat tibiae and were allowed to integrate for 4 weeks with or without the addition of the growth factor Bone Morphogenetic Protein and the bisphosphonate Zoledronic Acid. Samples were subjected to in situ pullout using high-resolution synchrotron x-ray tomography at the Tomcat beamline (SLS, PSI, Switzerland) at 30 keV with 25 ms exposure time, resulting in a total acquisition time of 45 s per scan, with a 3.6 μm isotropic voxel size. Using a custom-made loading device positioned inside the beamline, screws were pulled out with 0.05 mm increment, acquiring multiple scans until rupture of the sample. The in situ loading protocol was adapted to ensure short imaging time, which enabled multiple samples to be tested with short loading steps, while keeping the total testing time low and reducing dose deposition. Higher trabecular bone content was quantified in the surrounding of the screw in the treated groups, which correlated with increased mechanical strength and stiffness. Differences in screw implantation, such as contact between threads and cortex as well as minor tilt of the screw were also correlated to the mechanical parameters. In situ loading enabled the investigation of crack propagation during the pullout, highlighting the mechanical behavior of the interface. Three typical crack types were observed: (1) rupture at the interface of trabecular and cortical bone tissues, close to the screw, (2) large crack inside the cortex connected to the implant, and (3) first failure away from the screw with cracks propagating toward the screw-bone interface. Mechanical properties of in vivo integrated bone-metal screws rely on a combination of multiple parameters that are difficult to identify and separate one from the other.
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| 14. |
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| 15. |
- Mathavan, Neashan, et al.
(författare)
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Characterising Bone Material Composition and Structure in the Ovariectomized (OVX) Rat Model of Osteoporosis.
- 2015
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 97:2, s. 134-144
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Tidskriftsartikel (refereegranskat)abstract
- The ovariectomized (OVX) rat model is well established in investigations of osteoporosis and osteoporotic therapies. Advent of techniques such as Fourier-transform infrared (FTIR) spectroscopy and small angle X-ray scattering (SAXS) facilitate characterization of bone composition and mineral structure, respectively, which are key determinants of bone strength. Limited publications exist on the implementation of these techniques in the OVX rat model. At 12 weeks of age, female Sprague-Dawley rats were either sham-operated (n = 6) or ovariectomized (n = 6) and sacrificed 18 weeks later. L2 lumbar vertebrae and proximal tibiae were assessed by µCT, FTIR and SAXS. Presence of extensive trabecular deterioration in the µCT data confirmed the onset of osteoporosis. FTIR compositional parameters were determined including measures of degree of mineralization, crystallinity, collagen maturity and acid phosphate content. Mineral crystal thickness was determined from the SAXS data using two approaches available in literature. Compositionally, a decline in the heterogeneity of acid phosphate content was observed while measures of crystallinity and collagen maturity remained unaltered. Using an iterative curve fitting method, OVX-induced increases in the mineral crystal thickness of 3.8 and 7.8 % (p < 0.05) were noted in the trabecular of the vertebra and tibia, respectively. In conclusion, implementation of FTIR and SAXS techniques in the OVX rat model, identified no significant compositional changes while substantiating thickening of the mineral crystals as a general structural feature of OVX-induced osteoporosis in rats.
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| 16. |
- Mathavan, Neashan, et al.
(författare)
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The compositional and nano-structural basis of fracture healing in healthy and osteoporotic bone
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis, a prevalent metabolic bone disorder, predisposes individuals to increased susceptibility to fractures. It is also, somewhat controversially, thought to delay or impair the regenerative response. Using high-resolution Fourier-transform infrared spectroscopy and small/wide-angle X-ray scattering we sought to answer the following questions: Does the molecular composition and the nano-structure in the newly regenerated bone differ between healthy and osteoporotic environments? And how do pharmacological treatments, such as bone morphogenetic protein 7 (BMP-7) alone or synergistically combined with zoledronate (ZA), alter callus composition and nano-structure in such environments? Cumulatively, on the basis of compositional and nano-structural characterizations of newly formed bone in an open-osteotomy rat model, the healing response in untreated healthy and ovariectomy-induced osteoporotic environments was fundamentally the same. However, the BMP-7 induced osteogenic response resulted in greater heterogeneity in the nano-structural crystal dimensions and this effect was more pronounced with osteoporosis. ZA mitigated the effects of the upregulated catabolism induced by both BMP-7 and an osteoporotic bone environment. The findings contribute to our understanding of how the repair processes in healthy and osteoporotic bone differ in both untreated and treated contexts and the data presented represents the most comprehensive study of fracture healing at the nanoscale undertaken to date.
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| 17. |
- Semb, Gunvor, et al.
(författare)
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A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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| 18. |
- Silva Barreto, Isabella, et al.
(författare)
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Multiscale Characterization of Embryonic Long Bone Mineralization in Mice
- 2020
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Ingår i: Advanced Science. - : Wiley. - 2198-3844 .- 2198-3844. ; 7:21
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Tidskriftsartikel (refereegranskat)abstract
- Long bone mineralization occurs through endochondral ossification, where a cartilage template mineralizes into bone-like tissue with a hierarchical organization from the whole bone-scale down to sub-nano scale. Whereas this process has been extensively studied at the larger length scales, it remains unexplored at some of the smaller length scales. In this study, the changes in morphology, composition, and structure during embryonic mineralization of murine humeri are investigated using a range of high-resolution synchrotron-based imaging techniques at several length scales. With micro- and nanometer spatial resolution, the deposition of elements and the shaping of mineral platelets are followed. Rapid mineralization of the humeri occurs over approximately four days, where mineral to matrix ratio and calcium content in the most mineralized zone reach adult values shortly before birth. Interestingly, zinc is consistently found to be localized at the sites of ongoing new mineralization. The mineral platelets in the most recently mineralized regions are thicker, longer, narrower, and less aligned compared to those further into the mineralized region. In summary, this study demonstrates a specific spatial distribution of zinc, with highest concentration where new mineral is being deposited and that the newly formed mineral platelets undergo slight reshaping and reorganization during embryonic development.
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| 19. |
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| 20. |
- Tamminen, Inari S., et al.
(författare)
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Increased Heterogeneity of Bone Matrix Mineralization in Pediatric Patients Prone to Fractures: A Biopsy Study
- 2014
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 29:5, s. 1110-1117
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic osteoporosis (IOP) in children is characterized by fragility fractures and/or low bone mineral density in otherwise healthy individuals. The aim of the present work was to measure bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) in children with suspected IOP. Entire cross-sectional areas of transiliac bone biopsy samples from children (n=24, 17 boys; aged 6.7-16.6 years) with a history of fractures (n=14 with at least one vertebral fracture) were analyzed for cancellous (Cn) and cortical (Ct) BMDD. Outcomes were compared with normal reference BMDD data and correlated with the patients' clinical characteristics and bone histomorphometry findings. The subjects had similar average degree but significantly higher heterogeneity of mineralization in both Cn and Ct bone (Cn.CaWidth +23%, Ct.CaWidth +15%, p<0.001 and p=0.002, respectively), together with higher percentages of low mineralized cancellous (Cn.CaLow +35%, p<0.001) and highly mineralized cortical bone areas (Ct.CaHigh +82%, p=0.032). Ct.CaWidth and Ct.CaLow were positively correlated with mineralizing surface per bone surface (MS/BS; a primary histomorphometric determinant of bone formation) and with serum bone turnover markers (all p<0.05). The correlations of the mineralization heterogeneity with histomorphometric and serum bone turnover indices suggest that an enhanced variation in bone turnover/formation contributes to the increased heterogeneity of mineralization. However, it remains unclear whether the latter is cause for, or the response to the increased bone fragility in these children with suspected IOP. (c) 2014 American Society for Bone and Mineral Research.
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| 21. |
- Turunen, Mikael, et al.
(författare)
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Defect in fatty acid esterification of dolichol in Niemann-Pick type C1 mouse livers in vivo
- 2007
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1771:4, s. 506-513
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid esterification of dolichol and cholesterol in Niemann-Pick type C 1 mouse (Balb/c NIH npcl(-/-)) livers was investigated in response to treatment with peroxisomal proliferators. These inducers have hypolipidemic properties and influence the mevalonate pathway and the intracellular transport of the final products of this biosynthetic route. Such inducers are consequently interesting to use in a disease model with defective intracellular transport of lipids. In wild-type mice, the levels of dolichol and cholesterol found as free alcohols were not changed to any great extent upon treatment with the peroxisomal inducers dehydroepiandrosterone, clofibrate and diethylhexylphtalate. In contrast, the amounts of dolichyl esters increased whereas cholesteryl esters decreased by the same treatments. The rate of enzymatic esterification of dolichol in isolated microsomes was accordingly elevated after 5- to 7-day treatments with the efficient peroxisomal proliferators DEHP and PFOA, while the corresponding esterification of cholesterol was decreased. Upon peroxisomal induction in npcl(-/-) mice, the enzymatic dolichol esterification in vitro increased whereas the low concentration of dolichyl esters remained unchanged. The results thus demonstrate that the induction of fatty acid esterification of dolichol in vivo is impaired in npcl(-/-) mouse liver. It is therefore proposed that the intracellular lipid transport defect in npcl(-/-) mouse liver disables either dolichol and/or the fatty acid from reaching the site of esterification in vivo. This proposal was strengthened by the finding that the amount of dolichol was decreased in an isolated Golgi fraction from npcl(-/-) mice.
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| 22. |
- Turunen, Mikael, et al.
(författare)
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Hyperosmolaric contrast agents in cartilage tomography may expose cartilage to overload-induced cell death.
- 2012
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Ingår i: Journal of Biomechanics. - : Elsevier. - 0021-9290 .- 1873-2380. ; 45:3, s. 497-503
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Tidskriftsartikel (refereegranskat)abstract
- In clinical arthrographic examination, strong hypertonic contrast agents are injected directly into the joint space. This may reduce the stiffness of articular cartilage, which is further hypothesized to lead to overload-induced cell death. We investigated the cell death in articular cartilage while the tissue was compressed in situ in physiological saline solution and in full strength hypertonic X-ray contrast agent Hexabrix(TM). Samples were prepared from bovine patellae and stored in Dulbecco's Modified Eagle's Medium overnight. Further, impact tests with or without creep were conducted for the samples with contact stresses and creep times changing from 1 MPa to 10 MPa and from 0 min to 15 min, respectively. Finally, depth-dependent cell viability was assessed with a confocal microscope. In order to characterize changes in the biomechanical properties of cartilage as a result of the use of Hexabrix™, stress-relaxation tests were conducted for the samples immersed in Hexabrix™ and phosphate buffered saline (PBS). Both dynamic and equilibrium modulus of the samples immersed in Hexabrix™ were significantly (p<0.05) lower than those of the samples immersed in PBS. Cartilage samples immersed in physiological saline solution showed load-induced cell death primarily in the superficial and middle zones. However, under high 8-10 MPa contact stresses, the samples immersed in full strength Hexabrix™ showed significantly (p<0.05) higher number of dead cells than the samples compressed in physiological saline, especially in the deep zone of cartilage. In conclusion, excessive loading stresses followed by tissue creep might increase the risk for chondrocyte death in articular cartilage when immersed in hypertonic X-ray contrast agent, especially in the deep zone of cartilage.
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| 23. |
- Turunen, Mikael J., et al.
(författare)
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Bone mineral crystal size and organization vary across mature rat bone cortex
- 2016
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Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1047-8477. ; 195:3, s. 337-344
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Tidskriftsartikel (refereegranskat)abstract
- The macro- and micro-features of bone can be assessed by using imaging methods. However, nano- and molecular features require more detailed characterization, such as use of e.g., vibrational spectroscopy and X-ray scattering. Nano- and molecular features also affect the mechanical competence of bone tissue. The aim of the present study was to reveal the effects of mineralization and its alterations on the mineral crystal scale, by investigating the spatial variation of molecular composition and mineral crystal structure across the cross-section of femur diaphyses in young rats, and healthy and osteoporotic mature rats (N = 5). Fourier transform infrared spectroscopy and scanning small- and wide-angle X-ray scattering (SAXS/WAXS) techniques with high spatial resolution were used at identical locations over the whole cross-section. This allowed quantification of point-by-point information about the spatial distribution of mineral crystal volume. All measured parameters (crystal dimensions, degree of orientation and predominant orientation) varied across the cortex. Specifically, the crystal dimensions were lower in the central cortex than in the endosteal and periosteal regions. Mineral crystal orientation followed the cortical circumference in the periosteal and endosteal regions, but was less well-oriented in the central regions. Central cortex is formed rapidly during development through endochondral ossification. Since rats possess no osteonal remodeling, this bone remains (until old age). Significant linear correlations were observed between the dimensional and organizational parameters, e.g., between crystal length and degree of orientation (R2 = 0.83, p < 0.001). Application of SAXS/WAXS provides valuable information on bone nanostructure and its constituents, effects of diseases and, prospectively, mechanical competence.
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| 24. |
- Turunen, Mikael J., et al.
(författare)
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Composition and microarchitecture of human trabecular bone change with age and differ between anatomical locations
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 54:1, s. 118-125
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Tidskriftsartikel (refereegranskat)abstract
- The microarchitecture of trabecular bone adapts to its mechanical loading environment according to Wolff's law and alters with age. Trabecular bone is a metabolically active tissue, thus, its molecular composition and microarchitecture may vary between anatomical locations as a result of the local mechanical loading environment. No comprehensive comparison of composition and microarchitecture of trabecular bone in different anatomical locations has been conducted. Therefore, the objective of this study was to compare the molecular composition and microarchitecture, evaluated with Fourier transform infrared (FTIR) microspectroscopy and micro-computed tomography (mu CT), respectively, in the femoral neck, greater trochanter and calcaneus of human cadavers. Specimens were harvested from 20 male human cadavers (aged 17-82 years) with no known metabolic bone diseases. Significant differences were found in composition and microarchitecture of trabecular bone between the anatomical locations. Compositional differences were primarily observed between the calcaneus and the proximal femur sites. Mineralization was higher in the greater trochanter than in the calcaneus (+2%, p<0.05) and crystallinity was lowest in the calcaneus (-24%, p<0.05 as compared to the femoral neck). Variation in the composition of trabecular bone within different parts of the proximal femur was only minor. Collagen maturity was significantly lower in greater trochanter than in femoral neck (-8%, p<0.01) and calcaneus (-5%, p<0.05). The greater trochanter possessed a less dense trabecular bone microarchitecture compared to femoral neck or calcaneus. Age related changes were mainly found in the greater trochanter. Significant correlations were found between the composition and microarchitecture of trabecular bone in the greater trochanter and calcaneus, indicating that both composition and microarchitecture alter similarly. This study provides new information about composition and microarchitecture of trabecular bone in different anatomical locations and their alterations with age with respect to the anatomical loading environments. (C) 2013 Elsevier Inc. All rights reserved.
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| 25. |
- Turunen, Mikael J., et al.
(författare)
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Effects of tissue fixation and dehydration on tendon collagen nanostructure
- 2017
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Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1047-8477. ; 199:3, s. 209-215
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Tidskriftsartikel (refereegranskat)abstract
- Collagen is the most prominent protein in biological tissues. Tissue fixation is often required for preservation or sectioning of the tissue. This may affect collagen nanostructure and potentially provide incorrect information when analyzed after fixation. We aimed to unravel the effect of 1) ethanol and formalin fixation and 2) 24. h air-dehydration on the organization and structure of collagen fibers at the nano-scale using small and wide angle X-ray scattering. Samples were divided into 4 groups: ethanol fixed, formalin fixed, and two untreated sample groups. Samples were allowed to air-dehydrate in handmade Kapton pockets during the measurements (24. h) except for one untreated group. Ethanol fixation affected the collagen organization and nanostructure substantially and during 24. h of dehydration dramatic changes were evident. Formalin fixation had minor effects on the collagen organization but after 12. h of air-dehydration the spatial variation increased substantially, not evident in the untreated samples. Generally, collagen shrinkage and loss of alignment was evident in all samples during 24. h of dehydration but the changes were subtle in all groups except the ethanol fixed samples. This study shows that tissue fixation needs to be chosen carefully in order to preserve the features of interest in the tissue.
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| 26. |
- Turunen, Mikael J, et al.
(författare)
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Evaluation of composition and mineral structure of callus tissue in rat femoral fracture.
- 2014
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Ingår i: Journal of Biomedical Optics. - 1083-3668. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT. Callus formation is a critical step for successful fracture healing. Little is known about the molecular composition and mineral structure of the newly formed tissue in the callus. The aim was to evaluate the feasibility of small angle x-ray scattering (SAXS) to assess mineral structure of callus and cortical bone and if it could provide complementary information with the compositional analyses from Fourier transform infrared (FTIR) microspectroscopy. Femurs of 12 male Sprague-Dawley rats at 9 weeks of age were fractured and fixed with an intramedullary 1.1 mm K-wire. Fractures were treated with the combinations of bone morphogenetic protein-7 and/or zoledronate. Rats were sacrificed after 6 weeks and both femurs were prepared for FTIR and SAXS analysis. Significant differences were found in the molecular composition and mineral structure between the fracture callus, fracture cortex, and control cortex. The degree of mineralization, collagen maturity, and degree of orientation of the mineral plates were lower in the callus tissue than in the cortices. The results indicate the feasibility of SAXS in the investigation of mineral structure of bone fracture callus and provide complementary information with the composition analyzed with FTIR. Moreover, this study contributes to the limited FTIR and SAXS data in the field.
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| 27. |
- Turunen, Mikael J., et al.
(författare)
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Sub-trabecular strain evolution in human trabecular bone
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- To comprehend the most detrimental characteristics behind bone fractures, it is key to understand the material and tissue level strain limits and their relation to failure sites. The aim of this study was to investigate the three-dimensional strain distribution and its evolution during loading at the sub-trabecular level in trabecular bone tissue. Human cadaver trabecular bone samples were compressed in situ until failure, while imaging with high-resolution synchrotron radiation X-ray tomography. Digital volume correlation was used to determine the strains inside the trabeculae. Regions without emerging damage were compared to those about to crack. Local strains in close vicinity of developing cracks were higher than previously reported for a whole trabecular structure and similar to those reported for single isolated trabeculae. Early literature on bone fracture strain thresholds at the tissue level seem to underestimate the maximum strain magnitudes in trabecular bone. Furthermore, we found lower strain levels and a reduced ability to capture detailed crack-paths with increased image voxel size. This highlights the dependence between the observed strain levels and the voxel size and that high-resolution is needed to investigate behavior of individual trabeculae. Furthermore, low trabecular thickness appears to be one predictor of developing cracks. In summary, this study investigated the local strains in whole trabecular structure at sub-trabecular resolution in human bone and confirmed the high strain magnitudes reported for single trabeculae under loading and, importantly extends its translation to the whole trabecular structure.
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| 28. |
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| 29. |
- Törnquist, Elin, et al.
(författare)
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Mineralization of cortical bone during maturation and growth in rabbits
- 2019
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Ingår i: Journal of Bone and Mineral Metabolism. - : Springer Science and Business Media LLC. - 0914-8779 .- 1435-5604.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The composite nature of bone as a material governs its structure and mechanical behavior. How the collagenous matrix mineralizes, in terms of both mineral deposition and structure of the mineral crystals, is highly interesting when trying to elucidate the complex structural changes that occur during bone growth and maturation. We have previously looked at mineral deposition and structural evolution of the collagenous matrix, linking both to changes in mechanics. The purpose of this study was to provide specific information on changes in crystal size and organization as a function of growth and maturation. Materials and Methods: Using micro-computed tomography (µCT) and micro-focused scanning small-angle X-ray scattering (SAXS) we investigated cortical bone in two orthogonal directions relative to the long axis of the humeri of New Zealand White rabbits spanning from new-born to 6-months of age. We also investigated the changes with tissue age by looking at radial profiles of osteonal structures in the 6-months old rabbits. The findings were compared to our previous compositional, structural and mechanical data on the same sample cohort. Results: µCT showed a continuous mineral deposition up until 3-months of age, whilst the SAXS data showed an increase in both crystal thickness and degree of orientation up until 6-months of age. The osteonal profiles showed no statistically significant changes in crystal thickness. Conclusions: Comparison to previously collected mechanical data suggests that changes are not only explained by amount of mineral in the tissue but also by the crystal dimensions.
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| 30. |
- Wannberg, Gudmund, et al.
(författare)
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EISCAT_3D - a next-generation European radar system for upper atmosphere and geospace research
- 2010
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Ingår i: Radio Science Bulletin. - 1024-4530. ; :333, s. 75-88
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Tidskriftsartikel (refereegranskat)abstract
- The EISCAT Scientifi c Association, together with a number of collaborating institutions, has recently completed a feasibility and design study for an enhanced performance research radar facility to replace the existing EISCAT UHF and VHF systems. This study was supported by EU Sixth-Framework funding. The new radar retains the powerful multi-static geometry of the EISCAT UHF, but will employ phased arrays, direct-sampling receivers, and digital beamforming and beam steering. Design goals include, inter alia, a tenfold improvement in temporal and spatial resolution, an extension of the instantaneous measurement of full-vector ionospheric drift velocities from a single point to the entire altitude range of the radar, and an imaging capability to resolve small-scale structures. Prototype receivers and beamformers are currently being tested on a 48-element, 224 MHz array (the "Demonstrator") erected at the Kiruna EISCAT site, using the EISCAT VHF transmitter as an illuminator.
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| 31. |
- Williams, Jonathan A., et al.
(författare)
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Time course changes to structural, mechanical and material properties of bone in rats after complete spinal cord injury
- 2022
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Ingår i: Journal of Musculoskeletal Neuronal Interactions. - 1108-7161. ; 22:2, s. 212-234
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Characterise the spatiotemporal trabecular and cortical bone responses to complete spinal cord injury (SCI) in young rats. Methods: 8-week-old male Wistar rats received T9-transection SCI and were euthanised 2-, 6-, 10-or 16-weeks post-surgery. Outcome measures were assessed using micro-computed tomography, mechanical testing, serum markers and Fourier-transform infrared spectroscopy. Results: The trabecular and cortical bone responses to SCI are site-specific. Metaphyseal trabecular BV/TV was 59% lower, characterised by fewer and thinner trabeculae at 2-weeks post-SCI, while epiphyseal BV/TV was 23% lower with maintained connectivity. At later-time points, metaphyseal BV/TV remained unchanged, while epiphyseal BV/TV increased. The total area of metaphyseal and mid-diaphyseal cortical bone were lower from 2-weeks and between 6-and 10-weeks post-SCI, respectively. This suggested that SCI-induced bone changes observed in the rat model were not solely attributable to bone loss, but also to suppressed bone growth. No tissue mineral density differences were observed at any time-point, suggesting that decreased whole-bone mechanical properties were primarily the result of changes to the spatial distribution of bone. Conclusion: Young SCI rat trabecular bone changes resemble those observed clinically in adult and paediatric SCI, while cortical bone changes resemble paediatric SCI only.
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| 32. |
- Åkesson, Dan, et al.
(författare)
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Preparation of nanocomposites from biobased thermoset resins by UV-curing
- 2009
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Ingår i: Progress in organic coatings. - : Elsevier BV. - 0300-9440 .- 1873-331X. ; 67:3, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- Biobased thermoset resins were irradiated with utraviolet(UV) radiation in the presence of photoinitiators. Three different resins were evaluated-two resins were based on soybean oil and one was based on lactic acid. The cross-linking behaviour of these resins was characterized by real-time FTIR and Soxhlet extraction. All of the resins cured rapidly and formed rigid materials with a high degree of conversion. The cross-linked resins were characterized by mechanical testing, thermogravimetric analysis (TGA) as well as dynamic-mechanical thermal analysis (DMTA). The resins were reinforced with layered silicate, in order to form nanocomposite Structures. The resulting composites were characterized by DMTA and tensile testing. (C) 2009 Elsevier B.V. All rights reserved.
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| 33. |
- Åkesson, Dan, et al.
(författare)
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Synthesis and characterization of a lactic acid-based thermoset resin suitable for structural composites and coatings
- 2009
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Ingår i: Journal of Applied Polymer Science. - : John Wiley & Sons, Inc.. - 0021-8995 .- 1097-4628. ; 115:1, s. 480-486
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Tidskriftsartikel (refereegranskat)abstract
- A new biobased polyester resin was developed for thermoset composite applications. The resin is potentially inexpensive and can be produced industrially by relatively simple means. The resin consists of star-shaped methacrylated oligomers of lactic acid (LA). LA oligomers were synthesized in a two-step process: in the first step, oligomers of LA were polymerized by direct condensation of LA. In the second step, the oligomers were end-functionalized by methacrylic anhydride. The resin was characterized by differential scanning calorimetry, Raman spectroscopy, NMR, rubber process analyzer, and TOF-SIMS. Tests show that the resin can be crosslinked into a rigid network within a couple of minutes upon thermal initiation. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 115: 480-486, 2010
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| 34. |
- Åkesson, Dan, et al.
(författare)
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Thermoset lactic acid-based resin as a matrix for flax fibers
- 2010
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Ingår i: Journal of Applied Polymer Science. - : John Wiley & Sons, Inc.. - 0021-8995 .- 1097-4628. ; 119:5, s. 3004-3009
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Thermoset composites were produced from flax fibers and a novel lactic acid (LA)-based thermoset resin. This resin is based on methacrylated, star-shaped oligomers of LA. The main purpose of this work was to evaluate whether this resin can be used to produce structural composites from flax fibers. Composites were prepared by spray impregnation followed by compression molding at elevated temperature. The tests showed that composites can be produced with as much as 70 wt% fiber. The composites were evaluated by tensile testing, flexural testing, charpy impact test, dynamic mechanical thermal analysis (DMTA), and low-vacuum scanning electron microscopy. The ageing properties in high humid conditions were evaluated, the Young's modulus ranged from 3 GPa to 9 GPa in the best case. This work shows that structural composites can be produced from renewable material. It is clear from the results that these composites have properties that make them suitable for furniture, panels, or automotive parts.
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