| 1. |
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| 2. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 3. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Korhonen, Rami K., et al.
(författare)
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Multiscale In Silico Modeling of Cartilage Injuries
- 2023
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Ingår i: Advances in Experimental Medicine and Biology. - 2214-8019 .- 0065-2598. ; 1402, s. 45-56
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Bokkapitel (refereegranskat)abstract
- Injurious loading of the joint can be accompanied by articular cartilage damage and trigger inflammation. However, it is not well-known which mechanism controls further cartilage degradation, ultimately leading to post-traumatic osteoarthritis. For personalized prognostics, there should also be a method that can predict tissue alterations following joint and cartilage injury. This chapter gives an overview of experimental and computational methods to characterize and predict cartilage degradation following joint injury. Two mechanisms for cartilage degradation are proposed. In (1) biomechanically driven cartilage degradation, it is assumed that excessive levels of strain or stress of the fibrillar or non-fibrillar matrix lead to proteoglycan loss or collagen damage and degradation. In (2) biochemically driven cartilage degradation, it is assumed that diffusion of inflammatory cytokines leads to degradation of the extracellular matrix. When implementing these two mechanisms in a computational in silico modeling workflow, supplemented by in vitro and in vivo experiments, it is shown that biomechanically driven cartilage degradation is concentrated on the damage environment, while inflammation via synovial fluid affects all free cartilage surfaces. It is also proposed how the presented in silico modeling methodology may be used in the future for personalized prognostics and treatment planning of patients with a joint injury.
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| 5. |
- Kosonen, Joonas P., et al.
(författare)
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Injury-related cell death and proteoglycan loss in articular cartilage : Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines
- 2023
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is a common musculoskeletal disease that leads to deterioration of articular cartilage, joint pain, and decreased quality of life. When OA develops after a joint injury, it is designated as post-traumatic OA (PTOA). The etiology of PTOA remains poorly understood, but it is known that proteoglycan (PG) loss, cell dysfunction, and cell death in cartilage are among the first signs of the disease. These processes, influenced by biomechanical and inflammatory stimuli, disturb the normal cell-regulated balance between tissue synthesis and degeneration. Previous computational mechanobiological models have not explicitly incorporated the cell-mediated degradation mechanisms triggered by an injury that eventually can lead to tissue-level compositional changes. Here, we developed a 2-D mechanobiological finite element model to predict necrosis, apoptosis following excessive production of reactive oxygen species (ROS), and inflammatory cytokine (interleukin-1)-driven apoptosis in cartilage explant. The resulting PG loss over 30 days was simulated. Biomechanically triggered PG degeneration, associated with cell necrosis, excessive ROS production, and cell apoptosis, was predicted to be localized near a lesion, while interleukin-1 diffusion-driven PG degeneration was manifested more globally. Interestingly, the model also showed proteolytic activity and PG biosynthesis closer to the levels of healthy tissue when pro-inflammatory cytokines were rapidly inhibited or cleared from the culture medium, leading to partial recovery of PG content. The numerical predictions of cell death and PG loss were supported by previous experimental findings. Furthermore, the simulated ROS and inflammation mechanisms had longer-lasting effects (over 3 days) on the PG content than localized necrosis. The mechanobiological model presented here may serve as a numerical tool for assessing early cartilage degeneration mechanisms and the efficacy of interventions to mitigate PTOA progression.
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| 6. |
- Orozco, Gustavo A, et al.
(författare)
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Adaptation of Fibril-Reinforced Poroviscoelastic Properties in Rabbit Collateral Ligaments 8 Weeks After Anterior Cruciate Ligament Transection
- 2023
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 51:4, s. 726-740
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Tidskriftsartikel (refereegranskat)abstract
- Ligaments of the knee provide stability and prevent excessive motions of the joint. Rupture of the anterior cruciate ligament (ACL), a common sports injury, results in an altered loading environment for other tissues in the joint, likely leading to their mechanical adaptation. In the collateral ligaments, the patterns and mechanisms of biomechanical adaptation following ACL transection (ACLT) remain unknown. We aimed to characterize the adaptation of elastic and viscoelastic properties of the lateral and medial collateral ligaments eight weeks after ACLT. Unilateral ACLT was performed in six rabbits, and collateral ligaments were harvested from transected and contralateral knee joints after eight weeks, and from an intact control group (eight knees from four animals). The cross-sectional areas were measured with micro-computed tomography. Stepwise tensile stress-relaxation testing was conducted up to 6% final strain, and the elastic and viscoelastic properties were characterized with a fibril-reinforced poroviscoelastic material model. We found that the cross-sectional area of the collateral ligaments in the ACL transected knees increased, the nonlinear elastic collagen network modulus of the LCL decreased, and the amount of fast relaxation in the MCL decreased. Our results indicate that rupture of the ACL leads to an early adaptation of the elastic and viscoelastic properties of the collagen fibrillar network in the collateral ligaments. These adaptations may be important to consider when evaluating whole knee joint mechanics after ACL rupture, and the results aid in understanding the consequences of ACL rupture on other tissues.
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| 7. |
- Orozco, Gustavo A., et al.
(författare)
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Shear strain and inflammation-induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction : A computational study
- 2022
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 40:7, s. 1505-1522
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Tidskriftsartikel (refereegranskat)abstract
- Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage–synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies.
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| 8. |
- Dejea, Hector, et al.
(författare)
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In Situ Loading and Time-Resolved Synchrotron-Based Phase Contrast Tomography for the Mechanical Investigation of Connective Knee Tissues : A Proof-of-Concept Study
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Ingår i: Advanced Science. - 2198-3844.
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Tidskriftsartikel (refereegranskat)abstract
- Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time-resolved synchrotron-based X-ray phase-contrast tomography (SR-PhC-µCT) allows to capture the tissue dynamics. This proof-of-concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR-PhC-µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress–relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases.
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| 9. |
- Orozco, Gustavo A, et al.
(författare)
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A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait
- 2022
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.
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| 10. |
- Orozco, Gustavo A., et al.
(författare)
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Crack propagation in articular cartilage under cyclic loading using cohesive finite element modeling
- 2022
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Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- Severe joint injuries often involve cartilage defects that propagate after mechanical loading. The propagation of these lesions may contribute to the development of post-traumatic osteoarthritis (PTOA). However, the mechanisms behind their propagation remain unknown. Currently, no numerical predictive methods exist for estimating crack propagation in cartilage under cyclic loading, yet they would provide essential insights into crack growth in injured tissue after trauma. Here, we present a numerical approach to estimate crack propagation in articular cartilage under cyclic loading using a cohesive damage model. Four different material models for cartilage (hyperelastic, poro-hyperelastic, poro-hyper-viscoelastic, and fibril-reinforced poro-hyperelastic (FRPHE) with different collagen orientations) were implemented. Our numerical cohesive damage model was able to replicate the experimental crack length reported in the literature, showing greater crack length with an increasing number of loading cycles. Damage initiation stress (4.35–4.73 MPa) and fracture energy (0.97–1.55 N/mm) values obtained for the poro-hyperelastic, poro-hyper-viscoelastic, and parallel-FRPHE models were within the range of what has been reported previously. The crack growth predictions obtained by the FRPHE models showed the influence of anisotropy of the fibrillar matrix on the cartilage response. Our results indicate that our cohesive damage model could potentially be used to estimate the adverse conditions in injured soft tissue such as osteochondral lesions, menisci tears, or partial ligament ruptures under (ab)normal biomechanical scenarios.
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| 11. |
- Paz, Alexander, et al.
(författare)
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A novel knee joint model in FEBio with inhomogeneous fibril-reinforced biphasic cartilage simulating tissue mechanical responses during gait : data from the osteoarthritis initiative
- 2023
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Ingår i: Computer Methods in Biomechanics and Biomedical Engineering. - : Informa UK Limited. - 1025-5842 .- 1476-8259. ; 26:11, s. 1353-1367
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Tidskriftsartikel (refereegranskat)abstract
- We developed a novel knee joint model in FEBio to simulate walking. Knee cartilage was modeled using a fibril-reinforced biphasic (FRB) formulation with depth-wise collagen architecture and split-lines to account for cartilage structure. Under axial compression, the knee model with FRB cartilage yielded contact pressures, similar to reported experimental data. Furthermore, gait analysis with FRB cartilage simulated spatial and temporal trends in cartilage fluid pressures, stresses, and strains, comparable to those of a fibril-reinforced poroviscoelastic (FRPVE) material in Abaqus. This knee joint model in FEBio could be used for further studies of knee disorders using physiologically relevant loading.
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| 12. |
- Paz, Alexander, et al.
(författare)
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Expediting finite element analyses for subject‐specific studies of knee osteoarthritis : A literature review
- 2021
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Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 11:23
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Forskningsöversikt (refereegranskat)abstract
- Osteoarthritis (OA) is a degenerative disease that affects the synovial joints, especially the knee joint, diminishing the ability of patients to perform daily physical activities. Unfortunately, there is no cure for this nearly irreversible musculoskeletal disorder. Nowadays, many researchers aim for in silico‐based methods to simulate personalized risks for the onset and progression of OA and evaluate the effects of different conservative preventative actions. Finite element analysis (FEA) has been considered a promising method to be developed for knee OA management. The FEA pipe-line consists of three well‐established phases: pre‐processing, processing, and post‐processing. Cur-rently, these phases are time‐consuming, making the FEA workflow cumbersome for the clinical environment. Hence, in this narrative review, we overviewed present‐day trends towards clinical methods for subject‐specific knee OA studies utilizing FEA. We reviewed studies focused on understanding mechanisms that initiate knee OA and expediting the FEA workflow applied to the whole‐organ level. Based on the current trends we observed, we believe that forthcoming knee FEAs will provide nearly real‐time predictions for the personalized risk of developing knee OA. These analyses will integrate subject‐specific geometries, loading conditions, and estimations of local tissue mechanical properties. This will be achieved by combining state‐of‐the‐art FEA workflows with automated approaches aided by machine learning techniques.
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| 13. |
- Simkheada, Tulashi, et al.
(författare)
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Comparison of constitutive models for meniscus and their effect on the knee joint biomechanics during gait
- 2023
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Ingår i: Computer Methods in Biomechanics and Biomedical Engineering. - : Informa UK Limited. - 1025-5842 .- 1476-8259. ; 26:16, s. 2008-2021
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical behavior of meniscus can be modeled using constitutive material models of varying complexity, such as isotropic elastic or fibril reinforced poroelastic (FRPE). However, the FRPE material is complex to implement, computationally demanding in 3D geometries, and simulation is time-consuming. Hence, we aimed to quantify the most suitable and efficient constitutive model of meniscus for simulation of cartilage responses in the knee joint during walking. We showed that simpler constitutive material models can reproduce similar cartilage responses to a knee model with the FRPE meniscus, but only knee models that consider orthotropic elastic meniscus can also reproduce meniscus responses adequately.
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