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The incidence and morbidity of femoral fractures increases drastically with age. Femoral architecture and associated fracture risk are strongly influenced by loading during physical activities and it has been shown that the rate of loss of bone mineral density is significantly lower for active individuals than inactive. The objective of this work is to evaluate the impact of a cessation of some physical activities on elderly femoral structure and fracture behaviour. The authors previously established a biofidelic finite element model of the femur considered as a structure optimised to loading associated with daily activities. The same structural optimisation algorithm was used here to quantify the changes in bone architecture following cessation of stair climbing and sit-to-stand. Side fall fracture simulations were run on the adapted bone structures using a damage elasticity formulation. Total cortical and trabecular bone volume and failure load reduced in all cases of activity cessation. Bone loss distribution was strongly heterogeneous, with some locations even showing increased bone volume. This work suggests that maintaining the physical activities involved in the daily routine of a young healthy adult would help reduce the risk of femoral fracture in the elderly population by preventing bone loss.
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Densidade Óssea , Fraturas do Fêmur , Fêmur , Humanos , Fêmur/fisiologia , Fraturas do Fêmur/fisiopatologia , Idoso , Análise de Elementos Finitos , Masculino , Exercício Físico/fisiologia , FemininoRESUMO
The ultimate neural signal for muscle control is the neural drive sent from the spinal cord to muscles. This neural signal comprises the ensemble of action potentials discharged by the active spinal motoneurons, which is transmitted to the innervated muscle fibres to generate forces. Accurately estimating the neural drive to muscles in humans in vivo is challenging since it requires the identification of the activity of a sample of motor units (MUs) that is representative of the active MU population. Current electrophysiological recordings usually fail in this task by identifying small MU samples with over-representation of higher-threshold with respect to lower-threshold MUs. Here, we describe recent advances in electrophysiological methods that allow the identification of more representative samples of greater numbers of MUs than previously possible. This is obtained with large and very dense arrays of electromyographic electrodes. Moreover, recently developed computational methods of data augmentation further extend experimental MU samples to infer the activity of the full MU pool. In conclusion, the combination of new electrode technologies and computational modelling allows for an accurate estimate of the neural drive to muscles and opens new perspectives in the study of the neural control of movement and in neural interfacing.
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Eletromiografia , Neurônios Motores , Músculo Esquelético , Humanos , Músculo Esquelético/fisiologia , Músculo Esquelético/inervação , Eletromiografia/métodos , Neurônios Motores/fisiologia , Contração Muscular/fisiologia , Potenciais de Ação/fisiologia , Simulação por Computador , Modelos NeurológicosRESUMO
The computational simulation of human voluntary muscle contraction is possible with EMG-driven Hill-type models of whole muscles. Despite impactful applications in numerous fields, the neuromechanical information and the physiological accuracy such models provide remain limited because of multiscale simplifications that limit comprehensive description of muscle internal dynamics during contraction. We addressed this limitation by developing a novel motoneuron-driven neuromuscular model, that describes the force-generating dynamics of a population of individual motor units, each of which was described with a Hill-type actuator and controlled by a dedicated experimentally derived motoneuronal control. In forward simulation of human voluntary muscle contraction, the model transforms a vector of motoneuron spike trains decoded from high-density EMG signals into a vector of motor unit forces that sum into the predicted whole muscle force. The motoneuronal control provides comprehensive and separate descriptions of the dynamics of motor unit recruitment and discharge and decodes the subject's intention. The neuromuscular model is subject-specific, muscle-specific, includes an advanced and physiological description of motor unit activation dynamics, and is validated against an experimental muscle force. Accurate force predictions were obtained when the vector of experimental neural controls was representative of the discharge activity of the complete motor unit pool. This was achieved with large and dense grids of EMG electrodes during medium-force contractions or with computational methods that physiologically estimate the discharge activity of the motor units that were not identified experimentally. This neuromuscular model advances the state-of-the-art of neuromuscular modelling, bringing together the fields of motor control and musculoskeletal modelling, and finding applications in neuromuscular control and human-machine interfacing research.
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Contração Muscular , Músculo Esquelético , Humanos , Músculo Esquelético/fisiologia , Contração Muscular/fisiologia , Neurônios Motores/fisiologia , Simulação por Computador , Recrutamento Neurofisiológico/fisiologia , EletromiografiaRESUMO
The spinal motor neurons are the only neural cells whose individual activity can be noninvasively identified. This is usually done using grids of surface electromyographic (EMG) electrodes and source separation algorithms; an approach called EMG decomposition. In this study, we combined computational and experimental analyses to assess how the design parameters of grids of electrodes influence the number and the properties of the identified motor units. We first computed the percentage of motor units that could be theoretically discriminated within a pool of 200 simulated motor units when decomposing EMG signals recorded with grids of various sizes and interelectrode distances (IEDs). Increasing the density, the number of electrodes, and the size of the grids, increased the number of motor units that our decomposition algorithm could theoretically discriminate, i.e., up to 83.5% of the simulated pool (range across conditions: 30.5-83.5%). We then identified motor units from experimental EMG signals recorded in six participants with grids of various sizes (range: 2-36 cm2) and IED (range: 4-16 mm). The configuration with the largest number of electrodes and the shortest IED maximized the number of identified motor units (56 ± 14; range: 39-79) and the percentage of early recruited motor units within these samples (29 ± 14%). Finally, the number of identified motor units further increased with a prototyped grid of 256 electrodes and an IED of 2 mm. Taken together, our results showed that larger and denser surface grids of electrodes allow to identify a more representative pool of motor units than currently reported in experimental studies.
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Algoritmos , Neurônios Motores , Humanos , EletrodosRESUMO
The differentiation of fibroblasts into pathological myofibroblasts during wound healing is characterized by increased cell surface expression of αv-integrins. Our previous studies found that the deubiquitinase (DUB) USP10 removes ubiquitin from αv-integrins, leading to cell surface integrin accumulation, subsequent TGFß1 activation, and pathological myofibroblast differentiation. In this study, a yeast two-hybrid screen revealed a novel binding partner for USP10, the formin, DAAM1. We found that DAAM1 binds to and inhibits USP10's DUB activity through the FH2 domain of DAAM1 independent of its actin functions. The USP10/DAAM1 interaction was also supported by proximity ligation assay (PLA) in primary human corneal fibroblasts. Treatment with TGFß1 significantly increased USP10 and DAAM1 protein expression, PLA signal, and co-localization to actin stress fibers. DAAM1 siRNA knockdown significantly reduced co-precipitation of USP10 and DAAM1 on purified actin stress fibers, and ß1- and ß5-integrin ubiquitination. This resulted in increased αv-, ß1-, and ß5-integrin total protein levels, αv-integrin recycling, and extracellular fibronectin (FN) deposition. Together, our data demonstrate that DAAM1 inhibits USP10's DUB activity on integrins subsequently regulating cell surface αv-integrin localization and FN accumulation.
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Integrinas , Humanos , Actinas/metabolismo , Enzimas Desubiquitinantes/metabolismo , Forminas/metabolismo , Integrinas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , CicatrizaçãoRESUMO
Structural components designed to absorb energy and shield a more valuable structure ideally require mechanical properties that combine a relatively high load-carrying capacity followed by a practically zero stiffness. This ensures that a specified energy quantity may be absorbed within a limited displacement and that any stress transfer to the valuable structure is minimized. Material damage has been historically mobilized to provide such properties, but this obviously renders such components to be single-use. By contrast, mobilization of elastic instability can also provide the desired combination of properties but without necessarily damaging the material. This reveals an intriguing possibility of such components being potentially repairable and theoretically re-usable with no significant loss in performance. A series of analytical, finite-element and experimental studies are presented for a bespoke mechanical metamaterial arrangement that is designed to buckle sequentially and behave with the desired 'high strength-low stiffness' characteristic. It is found that the various axial and rotational stiffnesses associated with the geometric arrangement and its constituent connections may be tuned to provide the desired mechanical behaviour within the elastic range and delay the onset of significant damage, thereby rendering the concept of harnessing instability to be feasible.
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The association between combat-related traumatic injury (CRTI) and bone health is uncertain. A disproportionate number of lower limb amputees from the Iraq and Afghanistan conflicts are diagnosed with osteopenia/osteoporosis, increasing lifetime risk of fragility fracture and challenging traditional osteoporosis treatment paradigms. The aim of this study is to test the hypotheses that CRTI results in a systemic reduction in bone mineral density (BMD) and that active traumatic lower limb amputees have localized BMD reduction, which is more prominent with higher level amputations. This is a cross-sectional analysis of the first phase of a cohort study comprising 575 male adult UK military personnel with CRTI (UK-Afghanistan War 2003 to 2014; including 153 lower limb amputees) who were frequency-matched to 562 uninjured men by age, service, rank, regiment, deployment period, and role-in-theatre. BMD was assessed using dual-energy X-ray absorptiometry (DXA) scanning of the hips and lumbar spine. Femoral neck BMD was lower in the CRTI than the uninjured group (T-score -0.08 versus -0.42 p = .000). Subgroup analysis revealed this reduction was significant only at the femoral neck of the amputated limb of amputees (p = 0.000), where the reduction was greater for above knee amputees than below knee amputees (p < 0.001). There were no differences in spine BMD or activity levels between amputees and controls. Changes in bone health in CRTI appear to be mechanically driven rather than systemic and are only evident in those with lower limb amputation. This may arise from altered joint and muscle loading creating a reduced mechanical stimulus to the femur resulting in localized unloading osteopenia. This suggests that interventions to stimulate bone may provide an effective management strategy. © 2023 Crown copyright and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.
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Amputados , Doenças Ósseas Metabólicas , Osteoporose , Adulto , Masculino , Humanos , Densidade Óssea , Estudos de Coortes , Estudos Transversais , Resultado do TratamentoRESUMO
Deep learning biomechanical models perform optimally when trained with large datasets, however these can be challenging to collect in gait labs, while limited augmentation techniques are available. This study presents a data augmentation approach based on generative adversarial networks which generate synthetic motion capture (mocap) datasets of marker trajectories and ground reaction forces (GRFs). The proposed architecture, called adversarial autoencoder, consists of an encoder compressing mocap data to a latent vector, a decoder reconstructing the mocap data from the latent vector and a discriminator distinguishing random vectors from encoded latent vectors. Direct kinematics (DK) and inverse kinematics (IK) joint angles, GRFs, and inverse dynamics (ID) joint moments calculated for real and synthetic trials were compared using statistical parametric mapping to assure realistic data generation and select optimal architectural hyperparameters based on percentage average differences across the gait cycle length. We observed negligible differences for DK computed joint angles and GRFs, but not for inverse methods (IK: 29.2%, ID: 35.5%). When the same architecture was trained also including the joint angles calculated by IK, we found no significant differences in the kinematics and GRFs, and improvements in joint moments estimation (ID: 25.7%). Finally, we showed that our data augmentation approach improved the accuracy of joint kinematics (up to 23%, 0.8°) and vertical GRFs (11%) predicted by standard neural networks using a single simulated pelvic inertial measurement unit. These findings suggest that predictive deep learning models can benefit from the synthetic datasets produced with the proposed technique.
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Aprendizado Profundo , Fenômenos Biomecânicos , Marcha , Redes Neurais de ComputaçãoRESUMO
Our understanding of the firing behaviour of motoneuron (MN) pools during human voluntary muscle contractions is currently limited to electrophysiological findings from animal experiments extrapolated to humans, mathematical models of MN pools not validated for human data, and experimental results obtained from decomposition of electromyographical (EMG) signals. These approaches are limited in accuracy or provide information on only small partitions of the MN population. Here, we propose a method based on the combination of high-density EMG (HDEMG) data and realistic modelling for predicting the behaviour of entire pools of motoneurons in humans. The method builds on a physiologically realistic model of a MN pool which predicts, from the experimental spike trains of a smaller number of individual MNs identified from decomposed HDEMG signals, the unknown recruitment and firing activity of the remaining unidentified MNs in the complete MN pool. The MN pool model is described as a cohort of single-compartment leaky fire-and-integrate (LIF) models of MNs scaled by a physiologically realistic distribution of MN electrophysiological properties and driven by a spinal synaptic input, both derived from decomposed HDEMG data. The MN spike trains and effective neural drive to muscle, predicted with this method, have been successfully validated experimentally. A representative application of the method in MN-driven neuromuscular modelling is also presented. The proposed approach provides a validated tool for neuroscientists, experimentalists, and modelers to infer the firing activity of MNs that cannot be observed experimentally, investigate the neuromechanics of human MN pools, support future experimental investigations, and advance neuromuscular modelling for investigating the neural strategies controlling human voluntary contractions.
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Neurônios Motores , Músculo Esquelético , Animais , Eletromiografia/métodos , Humanos , Locomoção , Neurônios Motores/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologiaRESUMO
Our understanding of the behaviour of spinal alpha-motoneurons (MNs) in mammals partly relies on our knowledge of the relationships between MN membrane properties, such as MN size, resistance, rheobase, capacitance, time constant, axonal conduction velocity, and afterhyperpolarization duration. We reprocessed the data from 40 experimental studies in adult cat, rat, and mouse MN preparations to empirically derive a set of quantitative mathematical relationships between these MN electrophysiological and anatomical properties. This validated mathematical framework, which supports past findings that the MN membrane properties are all related to each other and clarifies the nature of their associations, is besides consistent with the Henneman's size principle and Rall's cable theory. The derived mathematical relationships provide a convenient tool for neuroscientists and experimenters to complete experimental datasets, explore the relationships between pairs of MN properties never concurrently observed in previous experiments, or investigate inter-mammalian-species variations in MN membrane properties. Using this mathematical framework, modellers can build profiles of inter-consistent MN-specific properties to scale pools of MN models, with consequences on the accuracy and the interpretability of the simulations.
Muscles receive their instructions through electrical signals carried by tens or hundreds of cells connected to the command centers of the body. These 'alpha-motoneurons' have various sizes and electrical characteristics which affect how they transmit signals. Previous experiments have shown that these properties are linked; for instance, larger motoneurons transfer electrical signals more quickly. The exact nature of the mathematical relationships between these characteristics, however, remains unclear. This limits our understanding of the behaviour of motoneurons from experimental data. To identify the equations linking eight motoneuron properties, Caillet et al. analysed published datasets from experimental studies on cat motoneurons. This approach uncovered simple mathematical associations: in fact, only one characteristic needs to be measured experimentally to calculate all the other properties. The relationships identified were also consistent with previously accepted approaches for modelling motoneuron activity. Caillet et al. then validated this mathematical framework with data from studies on rodents, showing that some of the equations hold true for different mammals. This work offers a quick and easy way for researchers to calculate the characteristics of a motoneuron based on a single observation. This will allow non-measured properties to be added to experimental datasets, and it could help to uncover the diversity of motoneurons at work within a population.
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Neurônios Motores , Medula Espinal , Animais , Ratos , Camundongos , Neurônios Motores/fisiologia , Medula Espinal/fisiologia , MamíferosRESUMO
BACKGROUND: Lumbar Disc Degeneration (LDD) is associated with recurrent low back pain (LBP) (symptomatic). However, in some instances of LDD, people do not experience LBP (asymptomatic). RESEARCH QUESTION: As a step towards understanding why some people with LDD experience LBP and others do not, the primary aim of this study was to examine differences in anticipatory (APA) and compensatory postural adjustments (CPA), between symptomatic LDD patients (LDD pain) and asymptomatic LDD controls (LDD no pain) during postural perturbation. The secondary aim was to determine simultaneous differences in mental health, disability and quality of life status. METHODS: 3 T MRI was used to acquire T2 weighted images (L1-S1) from LDD no pain (n = 34) and LDD pain groups (n = 34). In this observational study, responses to predicted and unpredicted forward perturbations were examined using three dimensional motion capture. A Mann Whitney U test was conducted to examine group differences in sagittal spine and lower limb kinematics (integrated angular displacements during four established APA and CPA time intervals), anxiety, depression, disability and quality of life. RESULTS: The LDD pain group exhibited lower hip and knee displacements (p = 0.049-0.040) than the LDD no pain group during predicted and unpredicted perturbation. The LDD pain group also exhibited higher compensatory lumbar displacement than the LDD no pain group (p = 0.040-0.005) in the predicted condition but there was no difference observed in the unpredicted condition. The LDD pain group experienced higher levels of depression, anxiety and disability (p < 0.0001) and lower quality of life (p = 0.0001) than LDD controls. SIGNIFICANCE: Symptomatic LDD patients are different from LDD controls; they exhibit different kinematic strategies, levels of disability, anxiety, depression and quality of life. Effective care may benefit from evaluating and targeting these differences.
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Degeneração do Disco Intervertebral , Dor Lombar , Fenômenos Biomecânicos , Humanos , Dor Lombar/complicações , Vértebras Lombares , Qualidade de VidaRESUMO
Purpose: Integrins play a central role in myofibroblast pathological adhesion, over-contraction, and TGFß activation. Previously, we demonstrated that after corneal wounding, αv integrins are protected from intracellular degradation by upregulation of the deubiquitinase USP10, leading to cell-surface integrin accumulation. Because integrins bind to and internalize extracellular matrix (ECM), we tested whether extracellular fibronectin (FN) accumulation can result from an increase in integrin and matrix recycling in primary human corneal fibroblasts (HCFs). Methods: Primary HCFs were isolated from cadaver eyes. HCFs were transfected with either USP10 cDNA or control cDNA by nucleofection. Internalized FN was quantified with a FN ELISA. Recycled extracellular integrin and FN were detected with streptavidin-488 by live cell confocal microscopy (Zeiss LSM 780). Endogenous FN extra domain A was detected by immunocytochemistry. Cell size and removal of FN from the cell surface was determined by flow cytometry. Results: USP10 overexpression increased α5ß1 (1.9-fold; P < 0.001) and αv (1.7-fold; P < 0.05) integrin recycling, with a concomitant increase in biotinylated FN internalization (2.1-fold; P < 0.05) and recycling over 4 days (1.7-2.2-fold; P < 0.05). The dependence of FN recycling on integrins was demonstrated by α5ß1 and αv integrin blocking antibodies, which, compared with control IgG, decreased biotinylated FN recycling (62% and 84%, respectively; P < 0.05). Overall, we established that extracellular FN was composed of approximately 1/3 recycled biotinylated FN and 2/3 endogenously secreted FN. Conclusions: Our data suggest that reduced integrin degradation with a subsequent increase in integrin/FN recycling after wounding may be a newly identified mechanism for the characteristic accumulation of ECM in corneal scar tissue.
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Córnea/metabolismo , Fibronectinas/metabolismo , Ubiquitina Tiolesterase/biossíntese , Adesão Celular , Membrana Celular/metabolismo , Células Cultivadas , Córnea/citologia , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Citometria de Fluxo , Humanos , Transdução de SinaisRESUMO
Public health organisations typically recommend a minimum amount of moderate intensity activities such as walking or cycling for two and a half hours a week, combined with some more demanding physical activity on at least 2 days a week to maintain a healthy musculoskeletal condition. For populations at risk of bone loss in the lumbar spine, these guidelines are particularly relevant. However, an understanding of how these different activities are influential in maintaining vertebral bone health is lacking. A predictive structural finite element modelling approach using a strain-driven algorithm was developed to study mechanical stimulus and bone adaptation in the lumbar spine under various physiological loading conditions. These loading conditions were obtained with a previously developed full-body musculoskeletal model for a range of daily living activities representative of a healthy lifestyle. Activities of interest for the simulations include moderate intensity activities involving limited spine movements in all directions such as, walking, stair ascent and descent, sitting down and standing up, and more demanding activities with large spine movements during reaching and lifting tasks. For a combination of moderate and more demanding activities, the finite element model predicted a trabecular and cortical bone architecture representative of a healthy vertebra. When more demanding activities were removed from the simulations, areas at risk of bone degradation were observed at all lumbar levels in the anterior part of the vertebral body, the transverse processes and the spinous process. Moderate intensity activities alone were found to be insufficient in providing a mechanical stimulus to prevent bone degradation. More demanding physical activities are essential to maintain bone health in the lumbar spine.
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Ocular scarring after surgery, trauma, or infection leads to vision loss. The transparent cornea is an excellent model system to test anti-scarring therapies. Cholesterol-conjugated fully modified asymmetric small interfering RNAs (siRNAs) (self-deliverable siRNAs [sdRNAs]) are a novel modality for in vivo gene knockdown, transfecting cells and tissues without any additional formulations. Myofibroblasts are a main contributor to scarring and fibrosis. αv integrins play a central role in myofibroblast pathological adhesion, overcontraction, and transforming growth factor ß (TGF-ß) activation. Previously, we demonstrated that αv integrins are protected from intracellular degradation after wounding by upregulation of the deubiquitinase (DUB) ubiquitin-specific protease 10 (USP10), leading to integrin cell surface accumulation. In this study, we tested whether knockdown of USP10 with a USP10-targeting sdRNA (termed US09) will reduce scarring after wounding a rabbit cornea in vivo. The wounded corneal stroma was treated once with US09 or non-targeting control (NTC) sdRNA. At 6 weeks US09 treatment resulted in faster wound closure, limited scarring, and suppression of fibrotic markers and immune response. Specifically, fibronectin-extra domain A (EDA), collagen III, and a-smooth muscle actin (p < 0.05), CD45+ cell infiltration (p < 0.01), and apoptosis at 24 (p < 0.01) and 48 h (p < 0.05) were reduced post-wounding. Corneal thickness and cell proliferation were restored to unwounded parameters. Targeting the DUB, USP10 is a novel strategy to reduce scarring. This study indicates that ubiquitin-mediated pathways should be considered in the pathogenesis of fibrotic healing.
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Balance recovery mechanisms are of paramount importance in situations like public transport where sudden loss of equilibrium can occur. These mechanisms can be altered by aging or pathological disorders. However it is almost impossible to investigate these phenomena in real-life conditions, and the safe environment of a laboratory is needed. This paper investigates how jerk perturbations in the transverse plane similar to those experienced on public transport can be simulated in a controlled manner. A platform capable of producing horizontal perturbations with a person standing on it was developed. Accuracy, repeatability, and load sensitivity of the system were assessed with repeated trials in all four directions of movement. Comparison between the destabilising effect experienced on public transport and the postural response to perturbations from the platform was also made by tracking acceleration of the centre of mass of four subjects in these two situations. Results show that balance perturbations representative of real-life situations, such as standing on public transport, can accurately and repeatedly be produced in a safe and controlled environment with a low-cost and low-maintenance system. Coupled to motion capture technology, the system can be used for pathology assessment and rehabilitation treatments.
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Movimento , Equilíbrio Postural/fisiologia , Ferrovias , Acelerometria , Adulto , Custos e Análise de Custo , Desenho de Equipamento , Feminino , Humanos , Masculino , Movimento (Física) , Reprodutibilidade dos TestesRESUMO
BACKGROUND: It is hypothesized that inherent differences in movement strategies exist between control subjects and those with a history of lower back pain (LBP). Previous motion analysis studies focus primarily on tracking spinal movements, neglecting the connection between the lower limbs and spinal function. Lack of knowledge surrounding the functional implications of LBP may explain the diversity in success from general treatments currently offered to LBP patients. OBJECTIVE: This pilot study evaluated the response of healthy controls and individuals with a history of LBP (hLBP) to a postural disturbance. METHODS: Volunteers (n= 26) were asked to maintain standing balance in response to repeated balance disturbances delivered via a perturbation platform while both kinematic and electromyographic data were recorded from the trunk, pelvis, and lower limb. RESULTS: The healthy cohort utilized an upper body-focused strategy for balance control, with substantial activation of the external oblique muscles. The hLBP cohort implemented a lower limb-focused strategy, relying on activation of the semitendinosus and soleus muscles. No significant differences in joint range of motion were identified. CONCLUSIONS: These findings suggest that particular reactive movement patterns may indicate muscular deficits in subjects with hLBP. Identification of these deficits may aid in developing specific rehabilitation programs to prevent future LBP recurrence.
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Dor Lombar/fisiopatologia , Extremidade Inferior/fisiopatologia , Coluna Vertebral/fisiopatologia , Tronco/fisiopatologia , Adulto , Fenômenos Biomecânicos/fisiologia , Estudos de Casos e Controles , Eletromiografia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Movimento , Músculo Esquelético/fisiopatologia , Projetos Piloto , Equilíbrio Postural/fisiologia , Postura/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto JovemRESUMO
Fetal kicking and movements generate biomechanical stimulation in the fetal skeleton, which is important for prenatal musculoskeletal development, particularly joint shape. Developmental dysplasia of the hip (DDH) is the most common joint shape abnormality at birth, with many risk factors for the condition being associated with restricted fetal movement. In this study, we investigate the biomechanics of fetal movements in such situations, namely fetal breech position, oligohydramnios and primiparity (firstborn pregnancy). We also investigate twin pregnancies, which are not at greater risk of DDH incidence, despite the more restricted intra-uterine environment. We track fetal movements for each of these situations using cine-MRI technology, quantify the kick and muscle forces, and characterise the resulting stress and strain in the hip joint, testing the hypothesis that altered biomechanical stimuli may explain the link between certain intra-uterine conditions and risk of DDH. Kick force, stress and strain were found to be significantly lower in cases of breech position and oligohydramnios. Similarly, firstborn fetuses were found to generate significantly lower kick forces than non-firstborns. Interestingly, no significant difference was observed in twins compared to singletons. This research represents the first evidence of a link between the biomechanics of fetal movements and the risk of DDH, potentially informing the development of future preventative measures and enhanced diagnosis. Our results emphasise the importance of ultrasound screening for breech position and oligohydramnios, particularly later in pregnancy, and suggest that earlier intervention to correct breech position through external cephalic version could reduce the risk of hip dysplasia.
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Luxação do Quadril , Articulação do Quadril , Fenômenos Mecânicos , Feminino , Luxação do Quadril/fisiopatologia , Articulação do Quadril/fisiopatologia , Humanos , Movimento , Gravidez , Fatores de Risco , Estresse MecânicoRESUMO
The pelvic construct is an important part of the body as it facilitates the transfer of upper body weight to the lower limbs and protects a number of organs and vessels in the lower abdomen. In addition, the importance of the pelvis is highlighted by the high mortality rates associated with pelvic trauma. This study presents a mesoscale structural model of the pelvic construct and the joints and ligaments associated with it. Shell elements were used to model cortical bone, while truss elements were used to model trabecular bone and the ligaments and joints. The finite element (FE) model was subjected to an iterative optimization process based on a strain-driven bone adaptation algorithm. The bone model was adapted to a number of common daily living activities (walking, stair ascent, stair descent, sit-to-stand, and stand-to-sit) by applying onto it joint and muscle loads derived using a musculoskeletal modeling framework. The cortical thickness distribution and the trabecular architecture of the adapted model were compared qualitatively with computed tomography (CT) scans and models developed in previous studies, showing good agreement. The sensitivity of the model to changes in material properties of the ligaments and joint cartilage and changes in parameters related to the adaptation algorithm was assessed. Changes to the target strain had the largest effect on predicted total bone volumes. The model showed low sensitivity to changes in all other parameters. The minimum and maximum principal strains predicted by the structural model compared to a continuum CT-derived model in response to a common test loading scenario showed good agreement with correlation coefficients of 0.813 and 0.809, respectively. The developed structural model enables a number of applications such as fracture modeling, design, and additive manufacturing of frangible surrogates.
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Osso Esponjoso/fisiologia , Osso Cortical/fisiologia , Análise de Elementos Finitos , Pelve/fisiologia , Fenômenos Biomecânicos , Osso Esponjoso/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Humanos , Ligamentos/diagnóstico por imagem , Ligamentos/fisiologia , Masculino , Pelve/diagnóstico por imagem , Estresse Mecânico , Tomografia Computadorizada por Raios X , Suporte de Carga , Adulto JovemRESUMO
Mechanical forces generated by fetal kicks and movements result in stimulation of the fetal skeleton in the form of stress and strain. This stimulation is known to be critical for prenatal musculoskeletal development; indeed, abnormal or absent movements have been implicated in multiple congenital disorders. However, the mechanical stress and strain experienced by the developing human skeleton in utero have never before been characterized. Here, we quantify the biomechanics of fetal movements during the second half of gestation by modelling fetal movements captured using novel cine-magnetic resonance imaging technology. By tracking these movements, quantifying fetal kick and muscle forces, and applying them to three-dimensional geometries of the fetal skeleton, we test the hypothesis that stress and strain change over ontogeny. We find that fetal kick force increases significantly from 20 to 30 weeks' gestation, before decreasing towards term. However, stress and strain in the fetal skeleton rises significantly over the latter half of gestation. This increasing trend with gestational age is important because changes in fetal movement patterns in late pregnancy have been linked to poor fetal outcomes and musculoskeletal malformations. This research represents the first quantification of kick force and mechanical stress and strain due to fetal movements in the human skeleton in utero, thus advancing our understanding of the biomechanical environment of the uterus. Further, by revealing a potential link between fetal biomechanics and skeletal malformations, our work will stimulate future research in tissue engineering and mechanobiology.
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Desenvolvimento Fetal/fisiologia , Feto , Desenvolvimento Musculoesquelético/fisiologia , Esqueleto , Estresse Fisiológico/fisiologia , Feminino , Feto/diagnóstico por imagem , Feto/embriologia , Humanos , Masculino , Esqueleto/diagnóstico por imagem , Esqueleto/embriologiaRESUMO
The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally. Therefore, the objective of this study was to develop simplified finite element models to investigate the mechanical behaviour and rupture of the fetal membrane, particularly its constituent layers, under various physiological conditions. It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviour compared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk of membrane rupture. Additionally, reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture) both resulted in increased membrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likely cause it to fail at term, during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of both normal and preterm rupture.