Combining the probabilistic finite element model and artificial neural network to study nutrient levels in the human intervertebral discs.

BACKGROUND: Diffusion distance and diffusivity are known to affect nutrient transport rates, but the probabilistic analysis of these two factors remains vacant. There is a lack of effective tools to evaluate disc nutrient levels. METHODS: Five-hundred-disc samples with different combinations of morphological and water content parameters were generated, which were used to evaluate nutrient levels in unloaded and loaded states. Spearman correlation coefficients between inputs and responses were calculated. Artificial neural networks were trained to predict nutrient concentrations based on the dataset generated by the probabilistic finite element model. FINDINGS: In unloaded and loaded states, the minimum oxygen concentration of nucleus pulposus was negatively correlated with disc height (r = -0.83, p < 0.01 and r = -0.76, p < 0.01, respectively), and the minimum glucose concentration of annulus fibrosus was positively correlated with its water content (r = 0.68, p < 0.01 and r = 0.73, p < 0.01, respectively). The maximum lactate concentration of cartilage endplate was affected by endplate thickness (r = 0.94, p < 0.01 and r = 0.95, p < 0.01, respectively). For trained neural networks, nutrient concentrations could be well predicted, with coefficients of determination greater than 0.95 and mean absolute percentage errors less than 5 %. INTERPRETATION: This study underscores the importance of disc height, annulus fibrosus water content, and endplate thickness in regulating nutrient levels, and precise control of these parameters should be prioritized in the design of tissue-engineered discs. Moreover, artificial neural networks might be a promising tool for evaluating nutrient levels.

Effect of compressive and tensile forces on glucose concentration and cell viability within the intervertebral disc: A finite element study.

Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.

Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities.

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Potential of electronic devices for detection of health problems in older adults at home: A systematic review and meta-analysis.

OBJECTIVE: The aim of this review was to evaluate the overall diagnostic performance of e-devices for detection of health problems in older adults at home. METHODS: A systematic review was conducted following the PRISMA-DTA guidelines. RESULTS: 31 studies were included with 24 studies included in meta-analysis. The included studies were divided into four categories according to the signals detected: physical activity (PA), vital signs (VS), electrocardiography (ECG) and other. The meta-analysis showed the pooled estimates of sensitivity and specificity were 0.94 and 0.98 respectively in the 'VS' group. The pooled sensitivity and specificity were 0.97 and 0.98 respectively in the 'ECG' group. CONCLUSIONS: All kinds of e-devices perform well in diagnosing the common health problems. While ECG-based health problems detection system is more reliable than VS-based ones. For sole signal detection system has limitation in diagnosing specific health problems, more researches should focus on developing new systems combined of multiple signals.

Biomechanical response of lumbar intervertebral disc in daily sitting postures: a poroelastic finite element analysis.

This study aims to establish and validate a poroelastic L4-L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.

Dynamic changes in mechanical properties of the adult rat spinal cord after injury.

Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.

Biomechanical effect of age-related structural changes on cervical intervertebral disc: A finite element study.

Previous literature has investigated the biomechanical response of healthy and degenerative discs, but the biomechanical response of suboptimal healthy intervertebral discs received less attention. The purpose was to compare the biomechanical responses and risk of herniation of young healthy, suboptimal healthy, and degenerative intervertebral discs. A cervical spine model was established and validated using the finite element method. Suboptimal healthy, mildly, moderately, and severely degenerative disc models were developed. Disc height deformation, range of motion, intradiscal pressure, and von Mises stress in annulus fibrosus were analyzed by applying a moment of 4 Nm in flexion, extension, lateral bending, and axial rotation with 100 N compressive loads. Disc height deformation in young healthy, suboptimal healthy, mildly, moderately, and severely degenerative discs was 40%, 37%, 21%, 12%, and 8%, respectively. The decreasing order of the range of motion was young healthy spine > suboptimal healthy spine > mildly degenerative spine > moderately degenerative spine > severely degenerative spine. The mean stress of annulus ground substance in the suboptimal healthy disc was higher than in the young healthy disc. The mean stress of inter-lamellar matrix and annulus ground substance in moderately and severely degenerative discs was higher than in other discs. Age-related structural changes and degenerative changes increased the stiffness and reduced the elastic deformation of intervertebral discs. Decreased range of motion due to the effects of aging or degeneration on the intervertebral disc, may cause compensation of adjacent segments and lead to progressive degeneration of multiple segments. The effect of aging on the intervertebral disc increased the risk of annulus fibrosus damage from the biomechanical point of view. Moderately and severely degenerative discs may have a higher risk of herniation due to the higher risk of damage and layers separation of annulus fibrosus caused by increased stress in the annulus ground substance and inter-lamellar matrix.

Effect of home-based exercise programs with e-devices on falls among community-dwelling older adults: a meta-analysis.

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72-0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

Effect of degenerative factors on cervical spinal cord during flexion and extension: a dynamic finite element analysis.

Spinal cord injury (SCI) is a global problem that brings a heavy burden to both patients and society. Recent investigations indicated degenerative disease is taking an increasing part in SCI with the growth of the aging population. However, little insight has been gained about the effect of cervical degenerative disease on the spinal cord during dynamic activities. In this work, a dynamic fluid-structure interaction model was developed and validated to investigate the effect of anterior and posterior encroachment caused by degenerative disease on the spinal cord during normal extension and flexion. Maximum von-Mises stress and maximum principal strain were observed at the end of extension and flexion. The abnormal stress distribution caused by degenerative factors was concentrated in the descending tracts of the spinal cord. Our finding indicates that the excessive motion of the cervical spine could potentially exacerbate spinal cord injury and enlarge injury areas. Stress and strain remained low compared to extension during moderate flexion. This suggests that patients with cervical degenerative disease should avoid frequent or excessive flexion and extension which could result in motor function impairment, whereas moderate flexion is safe. Besides, encroachment caused by degenerative factors that are not significant in static imaging could also cause cord compression during normal activities.

Effect of Velocity and Contact Stress Area on the Dynamic Behavior of the Spinal Cord Under Different Testing Conditions.

Knowledge of the dynamic behavior of the spinal cord under different testing conditions is critical for our understanding of biomechanical mechanisms of spinal cord injury. Although velocity and contact stress area are known to affect external mechanical stress or energy upon sudden traumatic injury, quantitative investigation of the two clinically relevant biomechanical variables is limited. Here, freshly excised rat spinal-cord-pia-arachnoid constructs were tested through indentation using indenters of different sizes (radii: 0.25, 0.50, and 1.00 mm) at various loading rates ranging from 0.04 to 0.20 mm/s. This analysis found that the ex vivo specimen displayed significant nonlinear viscoelasticity at <10% of specimen thickness depth magnitudes. At higher velocity and larger contact stress area, the cord withstood a higher peak load and exhibited more sensitive mechanical relaxation responses (i.e., increasing amplitude and speed of the drop in peak load). Additionally, the cord became stiffer (i.e., increasing elastic modulus) and softer (i.e., decreasing elastic modulus) at a higher velocity and larger contact stress area, respectively. These findings will improve our understanding of the real-time complex biomechanics involved in traumatic spinal cord injury.

The biomechanical effect of preexisting different types of disc herniation in cervical hyperextension injury.

OBJECTIVE: Preexisting severe cervical spinal cord compression is a significant risk factor in cervical hyperextension injury, and the neurological function may deteriorate after a slight force to the forehead. There are few biomechanical studies regarding the influence of pathological factors in hyperextension loading condition. The aim of this study is to analyze the effects of preexisting different types of cervical disc herniation and different degrees of compression on the spinal cord in cervical hyperextension. METHOD: A 3D finite element (FE) model of cervical spinal cord was modeled. Local type with median herniation, local type with lateral herniation, diffuse type with median herniation, and diffuse type with lateral herniation were simulated in neutral and extention positions. The compressions which were equivalent to 10%, 20%, 30%, and 40% of the sagittal diameter of the spinal cord were modeled. RESULTS: The results of normal FE model were consistent with those of previous studies. The maximum von Mises stresses appeared in the pia mater for all 32 loading conditions. The maximum von Mises stresses in extension position were much higher than in neutral position. In most cases, the maximum von Mises stresses in diffuse type were higher than in local type. CONCLUSION: Cervical spinal cord with preexisting disc herniation is more likely to be compressed in hyperextension situation than in neutral position. Diffuse type with median herniation may cause more severe compression with higher von Mises stresses concentrated at the anterior horn and the peripheral white matter, resulting in acute central cord syndrome from biomechanical point of view.

[Antitumer effect of supernatant from co-culture of human embryonic stem cells and breast cancer cells on MDA-MB-231 cells in vitro].

This study was designed to investigate the inhibitory effect of supernatant from co-culture of human embryonic stem cells and tumor MDA-MB-231 cells on the breast cancer. The direct co-culture system of human embryonic stem cells H9 and breast cancer MDA-MB-231 cells was established, and the supernatant was tested in the inhibition of MDA-MB-231 cells. The inhibitory effects were examined in tumor cell morphology using microscope, cell proliferation with MTT assay, and cell apoptosis using the Hoechst staining and flow cytometry. Transwell assay was used to detect the migration and invasion of tumor cells. The results suggest that the supernatant significantly inhibited the proliferation, invasion and migration, and promoted cell apoptosis of MDA-MB-231 cells. However, the supernatant of H9 cells alone had little effect on MDA-MB-231 cells. Therefore, we conclude that the supernatant of co-culture cells had an inhibitory effect on tumor cells in vitro.