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Dynamic loads have short and long-term effects in the rehabilitation of lower limb joints. However, an effective exercise program for lower limb rehabilitation has been debated for a long time. Cycling ergometers were instrumented and used as a tool to mechanically load the lower limbs and track the joint mechano-physiological response in rehabilitation programs. Current cycling ergometers apply symmetrical loading to the limbs, which may not reflect the actual load-bearing capacity of each limb, as in Parkinson's and Multiple Sclerosis diseases. Therefore, the present study aimed to develop a new cycling ergometer capable of applying asymmetric loads to the limbs and validate its function using human tests. The instrumented force sensor and crank position sensing system recorded the kinetics and kinematics of pedaling. This information was used to apply an asymmetric assistive torque only to the target leg using an electric motor. The performance of the proposed cycling ergometer was studied during a cycling task at three different intensities. It was shown that the proposed device reduced the pedaling force of the target leg by 19% to 40%, depending on the exercise intensity. This reduction in pedal force caused a significant reduction in the muscle activity of the target leg (p < 0.001), without affecting the muscle activity of the non-target leg. These results demonstrated that the proposed cycling ergometer device is capable of applying asymmetric loading to lower limbs, and thus has the potential to improve the outcome of exercise interventions in patients with asymmetric function in lower limbs.
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Ciclismo , Tecnologia Assistiva , Torque , Ciclismo/fisiologia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fenômenos Biomecânicos , Perna (Membro)/fisiologia , PéRESUMO
Machine learning-based activity and gait phase recognition algorithms are used in powered motion assistive devices to inform control of motorized components. The objective of this study was to develop a supervised multiclass classifier to simultaneously detect activity and gait phase (stance, swing) in real-world walking, stair ascent, and stair descent using inertial measurement data from the thigh and shank. The intended use of this algorithm was for control of a motion assistive device local to the knee. Using data from 80 participants, two decision trees and five long short-term memory (LSTM) models that each used different feature sets were initially tested and evaluated using a novel performance metric: proportion of perfectly classified strides (PPCS). Based on the PPCS of these initial models, five additional posthoc LSTM models were tested. Separate models were developed to classify (i) both activity and gait phase simultaneously (one model predicting six states), and (ii) activity-specific models (three individual binary classifiers predicting stance/swing phases). The superior activity-specific model had an accuracy of 98.0% and PPCS of 55.7%. The superior six-phase model used filtered inertial measurement data as its features and a median filter on its predictions and had an accuracy of 92.1% and PPCS of 22.9%. Pooling stance and swing phases from all activities and treating this model as a binary classifier, this model had an accuracy of 97.1%, which may be acceptable for real-world lower limb exoskeleton control if only stance and swing gait phases must be detected. Keywords: machine learning, deep learning, inertial measurement unit, activity recognition, gait.
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Marcha , Caminhada , Fenômenos Biomecânicos , Humanos , Articulação do Joelho , Aprendizado de MáquinaRESUMO
When runners impact the ground, they experience a sudden peak ground reaction force (GRF), which may be up to 4× greater than their bodyweight. Increased GRF impact peak magnitude has been associated with lower limb injuries in runners. Yet, shoe midsoles are capable of cushioning the impact between the runner and the ground to reduce GRF. It has been proposed that midsoles should be tunable with subject mass to minimize GRF and reduce risk of injury. Auxetic metamaterials, structures designed to achieve negative Poisson's ratios, demonstrate superior impact properties and are highly tunable. Recently, auxetic structures have been introduced in footwear, but their effects on GRF are not documented in literature. This work investigates the viability of a three-dimensional auxetic impact structure with a tunable force plateau as a midsole through mass-spring-damper simulation. An mass-spring-damper model was used to perform 315 simulations considering combinations of seven subject masses (45-90 kg), 15 auxetic plateau forces (72-1080 N), and three auxetic damping conditions (450, 725, and 1000 Ns/m) and regression analysis was used to determine their influence on GRF impact peak, energy, instantaneous, and average loading rate. Simulations showed that tuning auxetic plateau force and damping based on subject mass may reduce GRF impact and loading rate versus simulated conventional midsoles. Auxetic plateau force and damping conditions of 450 Ns/m and â¼1 bodyweight (BW), respectively, minimized peak impact GRF. This work demonstrates the need for tunable auxetic midsoles and may inform future work involving midsole testing.
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Sapatos , Fenômenos Biomecânicos , Simulação por ComputadorRESUMO
PURPOSE: To evaluate the effect of the braced arm-to-thigh technique (BATT) (versus self-selected techniques) on three-dimensional trunk kinematics and spinal loads for three common activities of daily living (ADLs) simulated in the laboratory: weeding (gardening), reaching for an object in a low cupboard, and car egress using the two-legs out technique. METHODS: Ten young healthy males performed each task using a self-selected technique, and then using the BATT. The pulling action of weeding was simulated using a magnet placed on a steel plate. Cupboard and car egress tasks were simulated using custom apparatus representing the dimensions of a kitchen cabinet and a medium-sized Australian car, respectively. Three-dimensional trunk kinematics and L4/L5 spinal loads were estimated using the Lifting Full-Body OpenSim model and compared between techniques. Paired t-tests were used to compare peak values between methods (self-selected vs BATT). RESULTS: The BATT significantly reduced peak extension moments (13-51%), and both compression (27-45%) and shear forces (31-62%) at L4/L5, compared to self-selected techniques for all three tasks (p < 0.05). Lateral bending angles increased with the BATT for weeding and cupboard tasks, but these changes were expected as the BATT inherently introduces asymmetric trunk motion. CONCLUSION: The BATT substantially reduced L4/L5 extension moments, and L4/L5 compression and shear forces, compared to self-selected methods, for three ADLs, in a small cohort of ten young healthy males without prior history of back pain. These study findings can be used to inform safe procedures for these three ADLs, as the results are considered representative of a mature population.
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Atividades Cotidianas , Coxa da Perna , Braço , Austrália , Fenômenos Biomecânicos , Humanos , Vértebras Lombares , Masculino , Coluna Vertebral , Suporte de CargaRESUMO
Some cyanobacteria, known as euendoliths, excavate and grow into calcium carbonates, with their activity leading to significant marine and terrestrial carbonate erosion and to deleterious effects on coral reef and bivalve ecology. Despite their environmental relevance, the mechanisms by which they can bore have remained elusive and paradoxical, in that, as oxygenic phototrophs, cyanobacteria tend to alkalinize their surroundings, which will encourage carbonate precipitation, not dissolution. Therefore, cyanobacteria must rely on unique adaptations to bore. Studies with the filamentous euendolith, Mastigocoleus testarum, indicated that excavation requires both cellular energy and transcellular calcium transport, mediated by P-type ATPases, but the cellular basis for this phenomenon remains obscure. We present evidence that excavation in M. testarum involves two unique cellular adaptations. Long-range calcium transport is based on active pumping at multiple cells along boring filaments, orchestrated by the preferential localization of calcium ATPases at one cell pole, in a ring pattern, facing the cross-walls, and by repeating this placement and polarity, a pattern that breaks at branching and apical cells. In addition, M. testarum differentiates specialized cells we call calcicytes, that which accumulate calcium at concentrations more than 500-fold those found in other cyanobacteria, concomitantly and drastically lowering photosynthetic pigments and enduring severe cytoplasmatic alkalinization. Calcicytes occur commonly, but not exclusively, in apical parts of the filaments distal to the excavation front. We suggest that calcicytes allow for fast calcium flow at low, nontoxic concentrations through undifferentiated cells by providing buffering storage for excess calcium before final excretion to the outside medium.
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Carbonato de Cálcio/metabolismo , Cianobactérias/citologia , Adaptação Fisiológica , Proteínas de Bactérias/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Recifes de Corais , Cianobactérias/metabolismo , TranscitoseRESUMO
Abnormal loading of the knee joint contributes to the pathogenesis of knee osteoarthritis. Gait retraining is a noninvasive intervention that aims to reduce knee loads by providing audible, visual, or haptic feedback of gait parameters. The computational expense of joint contact force prediction has limited real-time feedback to surrogate measures of the contact force, such as the knee adduction moment. We developed a method to predict knee joint contact forces using motion analysis and a statistical regression model that can be implemented in near real-time. Gait waveform variables were deconstructed using principal component analysis, and a linear regression was used to predict the principal component scores of the contact force waveforms. Knee joint contact force waveforms were reconstructed using the predicted scores. We tested our method using a heterogenous population of asymptomatic controls and subjects with knee osteoarthritis. The reconstructed contact force waveforms had mean (SD) root mean square differences of 0.17 (0.05) bodyweight compared with the contact forces predicted by a musculoskeletal model. Our method successfully predicted subject-specific shape features of contact force waveforms and is a potentially powerful tool in biofeedback and clinical gait analysis.
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Marcha/fisiologia , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Análise de Componente Principal , Adulto , Idoso , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/etiologia , Valor Preditivo dos TestesRESUMO
Both development and progression of knee osteoarthritis have been associated with the loading of the knee joint during walking. We are, therefore, interested in developing strategies for changing walking biomechanics to offload the knee joint without resorting to surgery. In this study, simulations of human walking were performed using a 2D bipedal forward dynamics model. A simulation generated by minimizing the metabolic cost of transport (CoT) resembled data measured from normal human walking. Three simulations targeted at minimizing the peak axial knee joint contact force instead of the CoT reduced the peak force by 12-25% and increased the CoT by 11-14%. The strategies used by the simulations were (1) reduction in gastrocnemius muscle force, (2) avoidance of knee flexion during stance, and (3) reduced stride length. Reduced gastrocnemius force resulted from a combination of changes in activation and changes in the gastrocnemius contractile component kinematics. The simulations that reduced the peak contact force avoided flexing the knee during stance when knee motion was unrestricted and adopted a shorter stride length when the simulated knee motion was penalized if it deviated from the measured human knee motion. A higher metabolic cost in an offloading gait would be detrimental for covering a long distance without fatigue but beneficial for exercise and weight loss. The predicted changes in the peak axial knee joint contact force from the simulations were consistent with estimates of the joint contact force in a human subject who emulated the predicted kinematics. The results demonstrate the potential of using muscle-actuated forward dynamics simulations to predict novel joint offloading interventions.
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Articulação do Joelho/fisiologia , Fenômenos Mecânicos , Modelos Biológicos , Caminhada/fisiologia , Adulto , Fenômenos Biomecânicos , Estudos de Viabilidade , Feminino , Marcha , Humanos , MasculinoRESUMO
BACKGROUND: The objective of this study was to investigate differences in tibiofemoral joint contact forces between individuals with moderate medial OA who exhibit radiographic knee OA progression within 3 years versus those who do not, and to understand the relationship between model-predicted contact forces and net external moments for this population. METHODS: 27 individuals with moderate medial compartment knee OA underwent baseline instrumented gait analysis. OA progressors were defined as those who experienced at least a one grade increase in medial joint space narrowing at three years. An electromyography-driven musculoskeletal model was used to estimate muscle and tibiofemoral contact forces at baseline, which were compared between progressors and non-progressors using t-tests. RESULTS: Seven individuals experienced radiographic OA progression by 3 years. Progressors walked with significantly higher peaks of medial and total tibiofemoral contact forces, and higher impulse of medial contact forces. Significant and high correlations were found between: first peaks of medial and total contact forces with first peak of the knee adduction moment (R2 = 0.74; R2 = 0.59); second peaks of medial and total knee contact forces with second peaks of knee adduction and flexion moments (R2 = 0.71; R2 = 0.68); medial knee contact force impulse with knee adduction moment impulse (R2 = 0.76). CONCLUSIONS: Higher tibiofemoral joint contact forces during walking were associated with three-year radiographic knee OA progression based on medial joint space narrowing. These results support the need for strategies that reduce compressive knee contact forces through the reduction of adduction and flexion moments during walking.
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Marcha , Osteoartrite do Joelho , Humanos , Marcha/fisiologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiologia , Caminhada/fisiologia , Joelho , Osteoartrite do Joelho/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Fenômenos BiomecânicosRESUMO
Lower limb tissue stiffness is contingent on various factors, including location, tissue composition, loading rates, and the geometry of the indenting object. Previous studies demonstrated that tissue stiffness varies greatly between individuals and between locations on an individual. Additionally, some studies have shown that activation of underlying muscle tissue increases bulk soft tissue stiffness. Yet, few studies have simultaneously considered both location and activation; this could be particularly important for measuring and predicting the function of devices such as prostheses and exoskeletons that interact with limbs at various locations during dynamic movement. In the present study, a custom handheld indentation device was used to explore changes in bulk leg tissue stiffness at rest and during isometric contractions. The indentation force-displacement curves were modelled using a Hertz model. At each level of activation (active/inactive), the shank had dramatically (â¼150%) greater tissue stiffness than the thigh (p < 0.001). However, results suggested location independence for stiffness ratio (active/inactive, p = 0.42); for either location, stiffness was approximately 2x greater for active vs inactive muscle. These results should be considered during the development of biomechanical models to simulate human tissue indentation stiffness across a range of activation states and locations.
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Membros Artificiais , Perna (Membro) , Fenômenos Biomecânicos , Humanos , Fenômenos Mecânicos , Movimento , Coxa da PernaRESUMO
Inhibitory neurosteroids, molecules generated in glia from circulating steroid hormones and de novo from cholesterol, keep seizures in check in epileptic animals. They can enhance inhibitory transmission mediated by gamma-aminobutyric acid receptors and have anticonvulsant action.
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Epilepsia/metabolismo , Neurotransmissores/metabolismo , Animais , Modelos Animais de Doenças , Eletroencefalografia/métodos , Inibidores Enzimáticos/efeitos adversos , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Feminino , Finasterida/efeitos adversos , Gonadotropinas/uso terapêutico , Lítio , Neurotransmissores/antagonistas & inibidores , Pilocarpus , Pregnanolona/uso terapêutico , RatosRESUMO
Objective: Off-loader knee braces have traditionally focused on redistributing loads away from either the medial or lateral tibiofemoral (TF) compartments. In this article, we study the potential of a novel "tricompartment unloader" (TCU) knee brace intended to simultaneously unload both the patellofemoral (PF) and TF joints during knee flexion. Three different models of the TCU brace are evaluated for their potential to unload the knee joint. Methods: A sagittal plane model of the knee was used to compute PF and TF contact forces, patellar and quadriceps tendon forces, and forces in the anterior and posterior cruciate ligaments during a deep knee bend (DKB) test using motion analysis data from eight participants. Forces were computed for the observed (no brace) and simulated braced conditions. A sensitivity and validity analysis was conducted to determine the valid output range for the model, and Statistical Parameter Mapping was used to quantify the effectual region of the different TCU brace models. Results: PF and TF joint force calculations were valid between ~0 and 100 degrees of flexion. All three simulated brace models significantly (p < 0.001) reduced predicted knee joint loads (by 30-50%) across all structures, at knee flexion angles >~30 degrees during DKB. Conclusions: The TCU brace is predicted to reduce PF and TF knee joint contact loads during weight-bearing activity requiring knee flexion angles between 30 and 100 degrees; this effect may be clinically beneficial for pain reduction or rehabilitation from common knee injuries or joint disorders. Future work is needed to assess the range of possible clinical and prophylactic benefits of the TCU brace.
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Despite the common use of one-handed lifting techniques for activities of daily living, these techniques have received little attention in the biomechanics literature. The braced arm-to-thigh technique (BATT) is a one-handed lifting method in which the dominant hand picks up objects, while the free hand braces the trunk on the ipsilateral thigh. The aim of this study was to compare the BATT to two-handed or unsupported one-handed lifting techniques with loads of 2 and 10 kg, by evaluating trunk motion and spine loading at L4/L5. Twenty healthy participants (30-70 years old) matched in age and sex to 18 participants with low back pain were recruited to the study. A three-axis load cell secured to the distal anterior thigh measured the bracing forces applied by the hand. The OpenSim Lifting Full-Body model was used to estimate trunk kinematics and spinal loading at L4/L5. Linear mixed-effects models were developed to compare trunk angles and L4/L5 moments and forces between lifting techniques. Trunk flexion angles were significantly reduced for the BATT lift compared to one-handed and two-handed stoop lifts (9-20%). However, the BATT also increased asymmetric trunk kinematics and moments at L4/L5. The BATT produced significantly lower moments (28-38%), and compressive (25-32%) and antero-posterior shear (25-45%) forces at L4/L5, compared to unsupported lifting techniques. Bracing the hand on the thigh to support the trunk can substantially reduce low back loading during lifting tasks of 2 to 10 kg.
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Braço , Braquetes , Remoção , Dor Lombar/fisiopatologia , Vértebras Lombares/fisiologia , Vértebras Lombares/fisiopatologia , Coxa da Perna , Atividades Cotidianas , Adulto , Idoso , Fenômenos Biomecânicos , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Suporte de CargaRESUMO
Injuries to the anterior cruciate ligament (ACL) and menisci commonly lead to early onset osteoarthritis. Treatments that can restore normative cartilage loading patterns may mitigate the risk of osteoarthritis, though it is unclear whether such a goal is achievable through conservative rehabilitation. We used musculoskeletal simulation to predict cartilage and ligament loading patterns during walking in intact, ACL deficient, menisci deficient, and ACL-menisci deficient knees. Stochastic simulations with varying coordination strategies were then used to test whether neuromuscular control could be modulated to restore normative knee mechanics in the pathologic conditions. During early stance, a 3â¯mm increase in anterior tibial translation was predicted in the ACL deficient knee. Mean cartilage contact pressure increased by 18% and 24% on the medial and lateral plateaus, respectively, in the menisci deficient knee. Variations in neuromuscular coordination were insufficient to restore normative cartilage contact patterns in either the ACL or menisci deficient knees. Elevated cartilage contact pressures in the pathologic knees were observed in regions where cartilage wear patterns have previously been reported. These results suggest that altered cartilage tissue loading during gait may contribute to region-specific degeneration patterns, and that varying neuromuscular coordination in isolation is unlikely to restore normative knee mechanics.
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Lesões do Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Sistema Nervoso Central/fisiologia , Lesões do Menisco Tibial/patologia , Lesões do Menisco Tibial/fisiopatologia , Caminhada/fisiologia , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Suporte de Carga , Adulto JovemRESUMO
The Static Optimization (SO) solver in OpenSim estimates muscle activations and forces that only equilibrate applied moments. In this study, SO was enhanced through an open-access MATLAB interface, where calculated muscle activations can additionally satisfy crucial mechanical stability requirements. This Stability-Constrained SO (SCSO) is applicable to many OpenSim models and can potentially produce more biofidelic results than SO alone, especially when antagonistic muscle co-contraction is required to stabilize body joints. This hypothesis was tested using existing models and experimental data in the literature. Muscle activations were calculated by SO and SCSO for a spine model during two series of static trials (i.e. simulation 1 and 2), and also for a lower limb model (supplementary material 2). In simulation 1, symmetric and asymmetric flexion postures were compared, while in simulation 2, various external load heights were compared, where increases in load height did not change the external lumbar flexion moment, but necessitated higher EMG activations. During the tasks in simulation 1, the predicted muscle activations by SCSO demonstrated less average deviation from the EMG data (6.8% -7.5%) compared to those from SO (10.2%). In simulation 2, SO predicts constant muscle activations and forces, while SCSO predicts increases in the average activations of back and abdominal muscles that better match experimental data. Although the SCSO results are sensitive to some parameters (e.g. musculotendon stiffness), when considering the strategy of the central nervous system in distributing muscle forces and in activating antagonistic muscles, the assigned activations by SCSO are more biofidelic than SO.
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Articulações/fisiologia , Modelos Biológicos , Músculo Esquelético/fisiologia , Fenômenos Biomecânicos , Feminino , Humanos , Extremidade Inferior/fisiologia , Masculino , Software , Coluna Vertebral/fisiologiaRESUMO
BACKGROUND: Braces for medial knee osteoarthritis can reduce medial joint loads through a combination of three mechanisms: application of an external brace abduction moment, alteration of gait dynamics, and reduced activation of antagonistic muscles. Although the effect of knee bracing has been reported independently for each of these parameters, no previous study has quantified their relative contributions to reducing medial knee loads. METHODS: In this study, we used a detailed musculoskeletal model to investigate immediate changes in medial and lateral loads caused by two different knee braces: OA Assist and OA Adjuster 3 (DJO Global). Seventeen osteoarthritis subjects and eighteen healthy controls performed overground gait trials in unbraced and braced conditions. RESULTS: Across all subjects, bracing reduced medial loads by 0.1 to 0.3 times bodyweight (BW), or roughly 10%, and increased lateral loads by 0.03 to 0.2 BW. Changes in gait kinematics due to bracing were subtle, and had little effect on medial and lateral joint loads. The knee adduction moment was unaltered unless the brace moment was included in its computation. Only one muscle, biceps femoris, showed a significant change in EMG with bracing, but this did not contribute to altered peak medial contact loads. CONCLUSIONS: Knee braces reduced medial tibiofemoral loads primarily by applying a direct, and substantial, abduction moment to each subject's knee. To further enhance brace effectiveness, future brace designs should seek to enhance the magnitude of this unloader moment, and possibly exploit additional kinematic or neuromuscular gait modifications.
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Braquetes , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/terapia , Adulto , Idoso , Fenômenos Biomecânicos/fisiologia , Estudos de Casos e Controles , Eletromiografia , Feminino , Marcha/fisiologia , Músculos Isquiossurais/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Adulto JovemRESUMO
The collagen fibers in the superficial layer of tibiofemoral articular cartilage exhibit distinct patterns in orientation revealed by split lines. In this study, we introduce a simulation framework to predict cartilage surface loading during walking to investigate if split line orientations correspond with principal strain directions in the cartilage surface. The two-step framework uses a multibody musculoskeletal model to predict tibiofemoral kinematics which are then imposed on a deformable surface model to predict surface strains. The deformable surface model uses absolute nodal coordinate formulation (ANCF) shell elements to represent the articular surface and a system of spring-dampers and internal pressure to represent the underlying cartilage. Simulations were performed to predict surface strains due to osmotic pressure, loading induced by walking, and the combination of both loading due to pressure and walking. Time-averaged magnitude-weighted first principal strain directions agreed well with split line maps from the literature for both the osmotic pressure and combined cases. This result suggests there is indeed a connection between collagen fiber orientation and mechanical loading, and indicates the importance of accounting for the pre-strain in the cartilage surface due to osmotic pressure.
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There is currently no validated full-body lifting model publicly available on the OpenSim modelling platform to estimate spinal loads during lifting. In this study, the existing full-body-lumbar-spine model was adapted and validated for lifting motions to produce the lifting full-body model. Back muscle activations predicted by the model closely matched the measured erector spinae activation patterns. Model estimates of intradiscal pressures and in vivo measurements were strongly correlated. The same spine loading trends were observed for model estimates and reported vertebral body implant measurements. These results demonstrate the suitability of this model to evaluate changes in lumbar loading during lifting.
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Remoção , Vértebras Lombares/fisiologia , Modelos Biológicos , Análise e Desempenho de Tarefas , Fenômenos Biomecânicos , Força Compressiva , Eletromiografia , Humanos , Disco Intervertebral/fisiologia , Masculino , Músculo Esquelético/fisiologia , Pressão , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Suporte de Carga , Adulto JovemRESUMO
In Caenorhabditis elegans, mutations in WDR-5 and other components of the COMPASS H3K4 methyltransferase complex extend lifespan and enable its inheritance. Here, we show that wdr-5 mutant longevity is itself a transgenerational trait that corresponds with a global enrichment of the heterochromatin factor H3K9me2 over twenty generations. In addition, we find that the transgenerational aspects of wdr-5 mutant longevity require the H3K9me2 methyltransferase MET-2, and can be recapitulated by removal of the putative H3K9me2 demethylase JHDM-1. Finally, we show that the transgenerational acquisition of longevity in jhdm-1 mutants is associated with accumulating genomic H3K9me2 that is inherited by their long-lived wild-type descendants at a subset of loci. These results suggest that heterochromatin facilitates the transgenerational establishment and inheritance of a complex trait. Based on these results, we propose that transcription-coupled H3K4me via COMPASS limits lifespan by encroaching upon domains of heterochromatin in the genome.
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Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Histona-Lisina N-Metiltransferase/genética , Padrões de Herança/genética , Longevidade/genética , Mutação , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Heterocromatina/genética , Heterocromatina/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Lisina/metabolismo , MetilaçãoRESUMO
Unloader braces are one non-invasive treatment of knee osteoarthritis, which primarily function by applying an external abduction moment to the joint to reduce loads in the medial compartment of the knee. We developed a novel method using brace deflection to estimate the mechanical effect of valgus braces and validated this model using strain gauge instrumentation. Three subjects performed static and walking trials, in which the moment applied by an instrumented brace was calculated using the deflection and strain methods. The deflection method predicted average brace moments of 8.7â¯Nm across static trials; mean error between the deflection model predictions and the gold-standard strain gauge measurements was 0.32â¯Nm. Mean brace moment predictions throughout gait ranged from 7.1 to 8.7â¯Nm using the deflection model. Maximum differences (MAE) over the gait cycle in mean and peak brace moments between methods were 1.50â¯Nm (0.96) and 0.60â¯Nm (0.42). Our proposed method enables quantification of brace abduction moments without the use of custom instrumentation. While the deflection-based method is similar to that implemented by Schmalz et al. (2010), the proposed method isolates abduction deflection from the 3 DOF angular changes that occur within the brace. Though the model should be viewed with more caution during swing (MAEâ¯=â¯1.16â¯Nm), it was shown that the accuracy is influenced by the uncertainty in angle measurement due to cluster spacing. In conclusion, the results demonstrate that the deflection-based method developed can predict comparable brace moments to those of the previously established strain method.
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Braquetes , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caminhada/fisiologia , Adulto JovemRESUMO
Valgus unloader braces are a conservative treatment option for medial compartment knee osteoarthritis that aim to unload the damaged medial compartment through application of an external abduction moment. Patient response to bracing is highly variable, however. While some experience improvements in pain, function, and joint loading, others receive little to no benefit. The objective of this work was to analyze clinical measures and biomechanical characteristics of unbraced walking to identify variables that are associated with the mechanical effectiveness of valgus unloader bracing. Seventeen patients with medial knee osteoarthritis walked overground with and without a valgus unloader brace. A musculoskeletal model was used to estimate the contact forces in the medial compartment of the tibiofemoral joint and brace effectiveness was defined as the decrease in peak medial contact force between unbraced and braced conditions. Stepwise linear regression was used to identify clinical and biomechanical measures that predicted brace effectiveness. The final regression model explained 77% of the variance in brace effectiveness using two variables. Bracing was more effective for those with greater peak external hip adduction moments and for those with higher Kellgren-Lawrence grades, indicating more severe radiographic osteoarthritis. The hip adduction moment was the best predictor of brace effectiveness and was well correlated with several other measures indicating that it may be functioning as a "biomarker" for good bracing candidates. CLINICAL SIGNIFICANCE: The ability to predict good candidates for valgus bracing may improve issues of patient compliance and could enable the ability to train patients to respond better to bracing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:351-356, 2018.