Prevalence of persistent SARS-CoV-2 in a large community surveillance study.

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

Exploring the Influence of Facet Orientation and Tropism on Neutral Zone Properties.

Lumbar spine pathologies have been linked independently to both neutral zone (NZ) properties and facet joint anatomical characteristics; however, the effect of facet joint orientation (FO) and tropism (FT) on NZ properties remains unclear. The aim of the present study was to investigate how axial plane FO and FT relate to NZ range and stiffness in the human lumbar spine and porcine cervical spine. Seven human lumbar functional spine units (FSUs) and 94 porcine cervical FSUs were examined. FO and FT were measured, and in vitro mechanical testing was used to determine anterior-posterior (AP) and flexion-extension (FE) NZ range and stiffness. FO and FT were found to have no significant relationship with AP and FE NZ range. Increases in FT were associated with greater FE and AP NZ stiffness in human FSUs, with no FT-NZ stiffness relationship observed in porcine specimens. A significant relationship (p < 0.001) between FO and FE NZ stiffness was observed for both porcine and human FSUs, with a more sagittal orientation of the facet joints being associated with decreased FE NZ stiffness. Given the link between NZ stiffness and pathological states of the lumbar spine, further research is warranted to determine the practical significance of the observed facet joint anatomical characteristic-NZ property relationship.

Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey.

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens.

Defining the lumbar and trunk-thigh neutral zone from the passive stiffness curve: application to hybrid sit-stand postures and chair design.

Minimal data exist on the neutral position for the lumbar spine, trunk, and thighs when adopting a hybrid posture. This study examined sex differences in the neutral zone lumbar stiffness and the lumbar and trunk-thigh angle boundaries of the neutral zone, and determined if the standing lumbar angle fell within the neutral zone. Passive lumbar flexion and extension moment-angle curves were generated for 31 participants (13 M, 18 F), pooled from two datasets, with trunk-thigh angles available for 10 participants. The neutral zone was defined as the low stiffness zone from both the flexion and extension curves. Males demonstrated significantly greater extensor stiffness. Neutral lumbar and trunk-thigh angles ranged on average -22.2 to 0.2° and 124.2 to 159.6° for males and -17.8 to -1.3° and 143.2 to 159.5° for females, respectively. Standing lumbar angles fell outside the neutral zone for 44% of participants. These neutral zone boundaries may inform kinematics for hybrid chair designs.Practitioner summary: Adoption of a neutral spinal posture may be achieved through hybrid chair design, yet minimal data exists on a physiologically defined neutral zone. Using measures of in vivo lumbar stiffness, the lumbar and trunk-thigh angular boundaries of the neutral zone were defined for both males and females.Abbreviations: EMG: electromyography; MVC: maximal voluntary contraction.

Characterizing the Mechanical and Viscoelastic Response of the Porcine Facet Joint Capsule Ligament in Response to a Simulated Impact.

The facet capsule ligament (FCL) is a structure in the lumbar spine that constrains motions of the vertebrae. Subfailure loads can produce microdamage resulting in increased laxity, decreased stiffness, and altered viscoelastic responses. Therefore, the purpose of this investigation was to determine the mechanical and viscoelastic properties of the FCL under various magnitudes of strain from control samples and samples that had been through an impact protocol. Two hundred FCL tissue samples were tested (20 control and 180 impacted). Impacted FCL tissue samples were obtained from functional spinal units that had been exposed to one of nine subfailure impact conditions. All specimens underwent the following loading protocol: preconditioning with five cycles of 5% strain, followed by a 30 s rest period, five cycles of 10% strain, and 1 cycle of 10% strain with a hold duration at 10% strain for 240 s (4 min). The same protocol was followed for 30% and 50% strain. Measures of stiffness, hysteresis, and force-relaxation were computed. No significant differences in stiffness were observed for impacted specimens in comparison to control. Impacted specimens from the 8 g flexed and 11 g flexed and neutral conditions exhibited greater hysteresis during the cyclic-30% and cyclic-50% portion of the protocol in comparison to controls. In addition, specimens from the 8 g and 11 g flexed conditions resulted in greater stress decay for the 50%-hold conditions. Results from this study demonstrate viscoelastic changes in FCL samples exposed to moderate and highspeed single impacts in a flexed posture.

Strain Response in the Facet Joint Capsule During Physiological Joint Rotation and Translation Following a Simulated Impact Exposure: An In Vitro Porcine Model.

Low back pain (LBP) is frequently reported following rear impact collisions. Knowledge of how the facet joint capsule (FJC) mechanically behaves before and after rear impact collisions may help explain LBP development despite negative radiographic evidence of gross tissue failure. This study quantified the Green strain tensor in the facet joint capsule during rotation and translation range-of-motion tests completed before and following an in vitro simulation of a rear impact collision. Eight FSUs (4 C3-C4, 4 C5-C6) were tested. Following a preload test, FSUs were flexed and extended at 0.5 deg/s until an ±8 N·m moment was achieved. Anterior and posterior joint translation was then applied at 0.2 mm/s until a target ±400 N shear load was imposed. Markers were drawn on the facet capsule surface and their coordinates were tracked during pre- and postimpact range-of-motion tests. Strain was defined as the change in point configuration relative to the determined neutral joint posture. There were no significant differences (p > 0.05) observed in all calculated FJC strain components in rotation and translation before and after the simulated impact. Our results suggest that LBP development resulting from the initiation of strain-induced mechanoreceptors and nociceptors with the facet joint capsule is unlikely following a severe rear impact collision within the boundaries of physiological joint motion.

Cervical Spine Motion Requirements From Night Vision Goggles May Play a Greater Role in Chronic Neck Pain than Helmet Mass Properties.

BACKGROUND: Chronic Neck Pain (CNP) among rotary-wing aircrew is thought to stem from night vision goggles (NVG) and counterweight (CW) systems which displace the centre of mass of the head. This investigation aimed to quantify the loads acting on the neck as a function of movement magnitude (MM), helmet conditions, and movement axes in rapid movements. METHODS: Cervical spine kinematics during rapid head repositioning tasks for flexion-extension (FE) and axial rotation (AR) movements were measured from 15 males and 15 females. Participants moved in either a 35° (Near MM) or 70° arc (Far MM), while donning a helmet, helmet with NVG, helmet with NVG and a typical CW, and a CW Liner (CWL). Measured EMG from three muscles bilaterally and used to drive a biomechanical model to quantify the compression and shear acting at the C5-C6 joint. RESULTS: In AR, the NVGs were associated with the largest compression magnitudes, 252 (24) N. CW conditions decreased the maximum compression to 249 (53) N. For FE, the compression was 340 N for the Far MM trials and 246 N for Near MMs. Changing the helmet configuration only modestly influenced these magnitudes in FE. CONCLUSION: Every 30° of MM increased compression by 57 to 105 N. The reduction of the moment of inertia by 16% in the CWL did not reduce reaction forces. Joint loads scaled proportionately with head-supported weight by a factor of 2.05. The magnitudes of loads suggest a cumulative loading pathway for CNP development.

A one-dimensional collagen-based biomechanical model of passive soft tissue with viscoelasticity and failure.

INTRODUCTION: Strains and sprains of soft tissues, including tendons and ligaments, are frequently occurring injuries. Musculoskeletal models show great promise in prediction and prevention of these injuries. However, these models rarely account for the viscoelastic properties of ligaments and tendons, much less their failure properties. The purpose of this project was to develop, simplify, and analyze a collagen-distribution model to address these limitations. MODEL DEVELOPMENT: A distribution-moment approximation was applied to an existing partial differential equation model to reduce its computational complexity. The resulting model was equipped with a Voigt model in series, which endowed it with viscoelastic properties in addition to failure properties. RESULTS: The model was able to reproduce the characteristic toe, linear, and failure regions ubiquitous throughout in-vitro tests on tissue specimens. In addition, it was able to reproduce a tri-phasic creep test consisting of an initial deformation, a steady-state, and failure. Stress-relaxation and hysteresis were also reproducible by the model. DISCUSSION AND CONCLUSION: The ability to reproduce so many characteristics of biological tissues suggests more bio-fidelity was achieved by the reduced model was other currently available models. Future work to further improve its bio-fidelity is proposed for specific tendons and ligaments.

Model-Aided Design of a Rear-Impact Collision Testing System for In Vivo Investigations.

A collision testing device used to simulate rear-end impacts on human volunteers was developed and validated. The testing device was designed using impact parameters obtained from real crash-test-derived vehicle-to-vehicle rear-end collisions. Experimental results show the proposed testing device achieves repeatable impact parameters well within the reported ranges of real vehicle-to-vehicle rear-end impact simulations reported in the literature. In particular, the device was able to produce a 7.66 (0.30) km/h delta-v collision with a duration of 111.6 (6.2) ms, and a 4.75 (0.29) g peak acceleration.

An Electromyographically Driven Cervical Spine Model in OpenSim.

Relatively few biomechanical models exist aimed at quantifying the mechanical risk factors associated with neck pain. In addition, there is a need to validate spinal-rhythm techniques for inverse dynamics spine models. Therefore, the present investigation was 3-fold: (1) the development of a cervical spine model in OpenSim, (2) a test of a novel spinal-rhythm technique based on minimizing the potential energy in the passive tissues, and (3) comparison of an electromyographically driven approach to estimating compression and shear to other cervical spine models. The authors developed ligament force-deflection and intervertebral joint moment-angle curves from published data. The 218 Hill-type muscle elements, representing 58 muscles, were included and their passive forces validated against in vivo data. Our novel spinal-rhythm technique, based on minimizing the potential energy in the passive tissues, disproportionately assigned motion to the upper cervical spine that was not physiological. Finally, using kinematics and electromyography collected from 8 healthy male volunteers, the authors calculated the compression at C7-T1 as a function of the head-trunk Euler angles. Differences from other models varied from 25.5 to 368.1 N. These differences in forces may result in differences in model geometry, passive components, number of degrees of freedom, or objective functions.

Cervical spine joint loading with neck flexion.

Cervical spine flexion is a common posture for those using computers, tablets, and smartphones; the latter being dubbed 'text-neck' in recent years. Coincidentally, flexion has been flagged as a significant mechanical risk factor for the development of chronic neck pain. Unfortunately, few modelling endeavours have attempted to quantify the intervertebral joint loads throughout the cervical spine in flexion, while still accounting for muscular activation. Eight healthy male subjects undertook five trials beginning in a neutral posture, flexed to 45 degrees, and returned to a neutral posture. 3 D head-trunk angles and surface electromyography from 10 neck muscles (5 bilaterally) were used as inputs into an inverse dynamic cervical spine model based on a 50th percentile male to compute the compression and anteroposterior (AP) shear forces for this flexion task. In general, compression increases cranially to caudally throughout the cervical spine, but levels off at the C5-C6 level. Conversely, in a neutral posture, there is a constant 18 N of anterior shear at each joint level. Compression increased twofold throughout the cervical spine with flexion, whereas anterior shear increased fourfold in the upper cervical spine and dramatically decreased caudally. The dramatic change in joint kinetics provides some mechanical evidence for the role of posture and interplay with muscle activity in the development of chronic neck pain. Results from this study can reinforce the need for appropriate workstation and monitor configurations and support the increased loading hypothesised to occur in 'text neck' postures. Practitioner summary: The purpose of this investigation was to quantify the compression and shear forces in the neck in 45 degrees of flexion compared to neutral. Flexion increased compression throughout the cervical spine 1.6-fold compared to a neutral posture. In the upper cervical spine, AP-shear increased four-fold compared to neutral. Abbreviation: AP: anteroposterior.

A Comparison of Clinical Spinal Mobility Measures to Experimentally Derived Lumbar Spine Passive Stiffness.

Spinal stiffness and mobility assessments vary between clinical and research settings, potentially hindering the understanding and treatment of low back pain. A total of 71 healthy participants were evaluated using 2 clinical assessments (posteroanterior spring and passive intervertebral motion) and 2 quantitative measures: lumped mechanical stiffness of the lumbar spine and local tissue stiffness (lumbar erector spinae and supraspinous ligament) measured via myotonometry. The authors hypothesized that clinical, mechanical, and local tissue measures would be correlated, that clinical tests would not alter mechanical stiffness, and that males would demonstrate greater lumbar stiffness than females. Clinical, lumped mechanical, and tissue stiffness were not correlated; however, gradings from the posteroanterior spring and passive intervertebral motion tests were positively correlated with each other. Clinical assessments had no effect on lumped mechanical stiffness. The males had greater lumped mechanical and lumbar erector spinae stiffness compared with the females. The lack of correlation between clinical, tissue, and lumped mechanical measures of spinal stiffness indicates that the use of the term "stiffness" by clinicians may require reevaluation; clinicians should be confident that they are not altering mechanical stiffness of the spine through segmental mobility assessments; and greater resting lumbar erector stiffness in males suggests that sex should be considered in the assessment and treatment of the low back.

The Impact of Posture on the Mechanical Properties of a Functional Spinal Unit During Cyclic Compressive Loading.

To assess how posture affects the transmission of mechanical energy up the spinal column during vibration, 18 porcine functional spinal units (FSUs) were exposed to a sinusoidal force (1500 ± 1200 N) at 5 Hz for 120 min in either a flexed, extended, or neutral posture. Force and FSU height were measured continuously throughout the collection. From these data, specimen height loss, dynamic stiffness, hysteresis, and parameters from a standard linear solid (SLS) model were determined and analyzed for differences between postures. Posture had an influence on all of these parameters. In extension, the FSU had higher dynamic stiffness values than when neutral or flexed (p < 0.0001). In flexion, the FSU had higher hysteresis than both an extended or neutral posture (p < 0.0001). Height loss was greatest in a flexed posture and smallest in an extended posture (p < 0.0001). In extension, the series spring element in the SLS model had a stiffness value higher than both flexed and neutral posture conditions, whereas the stiffness in the parallel spring was the same between extension and neutral (p < 0.01), both higher than in flexion. Viscosity coefficients were highest in extension compared to both flexed and neutral (p < 0.01). Based on these results, it was determined that posture had a significant influence in determining the mechanical properties of the spine when exposed to cyclic compressive loading.

A comparison of trunk biomechanics, musculoskeletal discomfort and productivity during simulated sit-stand office work.

Sedentary office work has been shown to cause low back discomfort and potentially cause injury. Prolonged standing work has been shown to cause discomfort. The implementation of a sit-stand paradigm is hypothesised to mitigate discomfort and prevent injury induced by prolonged exposure to each posture in isolation. This study explored the potential of sit-stand to reduce discomfort and prevent injury, without adversely affecting productivity. Twenty-four participants performed simulated office work in three different conditions: sitting, standing and sit-stand. Variables measured included: perceived discomfort, L4-L5 joint loading and typing/mousing productivity. Working in a sit-stand paradigm was found to have the potential to reduce discomfort when compared to working in a sitting or standing only configuration. Sit-stand was found to be associated with reduced lumbar flexion during sitting compared to sitting only. Increasing lumbar flexion during prolonged sitting is a known injury mechanism. Therefore, sit-stand exhibited a potentially beneficial response of reduced lumbar flexion that could have the potential to prevent injury. Sit-stand had no significant effect on productivity. Practitioner Summary: This study has contributed foundational elements to guide usage recommendations for sit-stand workstations. The sit-stand paradigm can reduce discomfort; however, working in a sit-stand ratio of 15:5 min may not be the most effective ratio. More frequent posture switches may be necessary to realise the full benefit of sit-stand.

Strain inhibition of bacterial collagenase is consistent with a collagen fibril uncrimping mechanism in rat tail tendons.

Mechanical strain inhibits bacterial collagenase from cleaving collagen. Additionally, the toe region of a soft tissue's force-elongation curve arises from sequentially engaging collagen fibrils as the tissue lengthens. Together, these phenomena suggest that mechanical strain may gradually inhibit collagenase activity through a soft tissue's toe region. Therefore, this investigation sought to test this hypothesis. 92 rat tail tendon fascicles from 3 female sentinel animals underwent preliminary stiffness tests, and their force-elongation curves were fit to a collagen distribution model. This distribution-based model calculated the force magnitude corresponding to p% of collagen fibril engagement. Specimens were separated into one of five levels of p, and that level of force was maintained for two hours while being exposed to 0.054 U/mL of bacterial collagenase from C. histolyticum. The specimens were strained to failure following the creep test, and the relative reduction in stiffness was quantified to estimate the fraction of digested fibrils. Every 10% additional collagen engagement corresponded to a 6.3% (97% highest density interval: 4.3 - 8.4%) retention of stiffness, which indicated collagenase inhibition. The results of this investigation were consistent with a strain-inhibition hypothesis along with the established uncrimping mechanism in the toe region. These results support an interaction between mechanical strain and collagenolysis, which may be valuable for disease prevention or treatment.

Lower limb postures resembling sitting and standing alter lumbar angles along the passive stiffness curve.

In vivo lumbar passive stiffness is often used to assess time-dependent changes in lumbar tissues and to define the neutral zone. We tested the hypothesis that flexing the hips would alter tension in hip and spine musculature, leading to a more extended passive stiffness curve (i.e., right-shifted), without changes in lumbar stiffness. Twenty participants underwent side-lying passive testing with the lower limbs positioned in Stand, Kneel, and Sit representative postures. Moment-angle curves were constructed from the lumbar angles and the moment at L4/5 and partitioned into three zones. Partially supporting our hypothesis, lumbar stiffness within the low and transition stiffness zones was similar between the Stand and Sit. Contrary to our hypothesis, lumbar angles were significantly larger in the Sit compared to the Stand and Kneel postures at the first and second breakpoints, with average differences of 9.3° or 27.2% of passive range of motion (%PassRoM) in flexion and 5.6° or 16.6 %PassRoM in extension. Increased flexion in the Sit may be linked to increased posterior pelvic tilt and associated lower lumbar vertebrae flexion. Investigators must ensure consistent pelvis and hip positioning when measuring lumbar stiffness. Additionally, the adaptability of the neutral zone to pelvis posture, particularly between standing and sitting, should be considered in ergonomic applications.

Head supported mass, moment of inertia, neck loads and stability: A simulation study.

Occupations or activities where donning head-supported mass (HSM) is commonplace put operators at an elevated risk of chronic neck pain. Yet, there is no consensus about what features of HSM influence the relative contributions to neck loads. Therefore, we tested four hypotheses that could increase neck loads: (i) HSM increases gravitational moments; (ii) more muscle activation is required to stabilize the head with HSM; (iii) the position of the HSM centre of mass (COM) induces gravitational moments; and (iv) the added moment of inertia (MOI) from HSM increases neck loads during head repositioning tasks. We performed a sensitivity analysis on the C5-C6 compression evaluated from a 24-degree freedom cervical spine model in OpenSim for static and dynamic movement trials. For static trials, we varied the magnitude of HSM, the position of its COM, and developed a novel stability constraint for static optimization. In dynamic trials, we varied HSM and the three principle MOIs. HSM magnitude and compression were linearly related to one another for both static and dynamic trials, with amplification factors varying between 1.9 and 3.9. Similar relationships were found for the COM position, although the relationship between C5-C6 peak compression and MOI in dynamic trials was generally nonlinear. This sensitivity analysis uncovered evidence in favour of hypotheses (i), (ii) and (iii). However, the model's prediction of C5-C6 compression was not overly sensitive to the magnitude of MOI. Therefore, the HSM mass properties may be more influential on neck compression than MOI properties, even during dynamic tasks.

[Modeling and simulation activities to design sampling scheme for population pharmacokinetic study on amlodipine].

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.

Are rotational passive stiffness and translational passive stiffness correlated? A porcine in vitro study.

BACKGROUND: Qualitative clinical assessments of spinal stiffness have been demonstrated to show moderate correlations with one-another. We hypothesized that these correlations would improve in an in vitro model of the functional spinal unit. If the stiffness of spinal units are different across loading regimes (e.g. flexion-extension versus shear), then it may provide one explanation as to the variability in findings from clinical assessments, since these tests tend not to discriminate rotational and translational degrees-of-freedom. Therefore, the purpose of this investigation was to quantify the relationships between rotational and translational stiffness measures in vitro. METHODS: Forty-eight porcine cervical spine functional units were used in this investigation (20 C3-C4, 28 C5-C6). While under constant 300 N compressive load, range-of-motion tests for both flexion-extension (± 8 Nm, 0.5 deg./s) and anteroposterior shear (± 400 N, 0.2 mm/s) were conducted, to quantify moment-angle and force-deflection curves. Representative stiffness values were then obtained for flexion, extension, anterior shear, and posterior shear using segmented regression. The correlation matrix between these four measures was then used to explore their potential relationships. FINDINGS: Of the six correlations conducted, only the relationship between posterior shear and extension stiffness was statistically significant (p = 0.014), despite featuring a low correlation coefficient (R2 = 0.123). INTERPRETATION: The poor correlations between stiffness metrics in this study supports the disparate findings of tissue stiffness in vivo. Results from this investigation suggest that clinicians should be cognizant of which degrees-of-freedom they are assessing in the spine, as their stiffness values vary independently.

Cyclic loading history alters the joint compression tolerance and regional indentation responses in the cartilaginous endplate.

This study quantified the effect of subthreshold loading histories that differed by joint posture (neutral, flexed), peak loading variation (10%, 20%, 40%), and loading duration (1000, 3000, 5000 cycles) on the post-loading Ultimate Compressive Tolerance (UCT), yield force, and regional Cartilaginous End Plate (CEP) indentation responses (loading stiffness and creep displacement). One hundred and fourteen porcine spinal units were included. Following conditioning and cyclic compression exposures, spinal units were transected and one endplate from each vertebra underwent subsequent UCT or microindentation testing. UCT testing was conducted by compressing a single vertebra at a rate of 3 kN/s using an indenter fabricated to a representative intervertebral disc size and shape. Force and actuator position were sampled at 100 Hz. Non-destructive uniaxial CEP indentation was performed at five surface locations (central, anterior, posterior, right, left) using a Motoman robot and aluminum indenter (3 mm hemisphere). Force and end-effector position were sampled at 10 Hz. A significant three-way interaction was observed for UCT (p = 0.038). Compared to neutral, the UCT was, on average, 1.9 kN less following each flexed loading duration. No effect of variation was observed in flexion; however, 40% variation caused the UCT to decrease by an average of 2.13 kN and 2.06 kN following 3000 and 5000 cycles, respectively. The indentation stiffness in the central CEP mimicked the UCT response. These results demonstrate a profound effect of posture on post-loading UCT and CEP behaviour. Control of peak compression exposures became particularly relevant only when a neutral posture was maintained and beyond the midpoint of the predicated lifespan.