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Repetitive impacts encountered during locomotion may be modified by footwear and/or surface. Changes in kinematics may occur either as a direct response to altered mechanical conditions or over time as active adaptations. PURPOSE:: To investigate how midsole hardness, surface stiffness, and running duration influence running kinematics. METHODS: In the first of two experiments, 12 males ran at metabolic steady state under six conditions; combinations of midsole hardness (40 Shore A, 70 Shore A), and surface stiffness (100 kN x m, 200 kN x m, and 350 kN x m). In the second experiment, 10 males ran for 30 min on a 12% downhill grade. In both experiments, subjects ran at 3.4 m x s on a treadmill while 2-D hip, knee, and ankle kinematics were determined using high-speed videography (200 Hz). Oxygen cost and heart rate data were also collected. Kinematic adaptations to midsole, surface, and running time were studied. RESULTS: Stance time, stride cycle time, and maximal knee flexion were invariant across conditions in each experiment. Increased midsole hardness resulted in greater peak ankle dorsiflexion velocity (P = 0.0005). Increased surface stiffness resulted in decreased hip and knee flexion at contact, reduced maximal hip flexion, and increased peak angular velocities of the hip, knee, and ankle. Over time, hip flexion at contact decreased, plantarflexion at toe-off increased, and peak dorsiflexion and plantarflexion velocity increased. CONCLUSION: Lower-extremity kinematics adapted to increased midsole hardness, surface stiffness, and running duration. Changes in limb posture at impact were interpreted as active adaptations that compensate for passive mechanical effects. The adaptations appeared to have the goal of minimizing metabolic cost at the expense of increased exposure to impact shock. [ABSTRACT FROM AUTHOR]

Aims: DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions., Methods: Four representative low-grade gliomas of distinct histologies were centrally selected, and DNA extraction was performed. Participating laboratories received a DNA aliquot and performed the DNA methylation-based classification and result interpretation without knowledge of tumour histology. Additionally, participants were required to interpret the copy number profile derived from DNA methylation data and conduct DNA sequencing of the BRAF hotspot p.V600 due to its relevance for low-grade gliomas. Results had to be returned within 30 days., Results: High technical reproducibility was observed, with a median pairwise correlation of 0.99 (range 0.94-0.99) between coordinating laboratory and participants. DNA methylation-based tumour classification and copy number profile interpretation were consistent across all centres, and BRAF mutation status was accurately reported for all cases. Eleven out of 12 centres successfully reported their analysis within the 30-day timeframe., Conclusion: Our study demonstrates remarkable concordance in DNA methylation profiling and profile interpretation across 12 international centres. These findings underscore the potential contribution of DNA methylation analysis to the harmonisation of brain tumour diagnostics., (© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Objective: The objective of this study was to assess the feasibility of monitoring and diagnosing compromised walking motion in the frontal plane, particularly in persons living with the chronic effects of stroke (PwCS). The study aimed to determine whether active control of walking in the frontal plane could be monitored and provide diagnostic insights into compensations made by PwCS during community living., Methods: The study recruited PwCS with noticeable walking asymmetries and employed a monitoring method to assess frontal plane motion. Monitoring was conducted both within a single assessment and between assessments. The study aimed to uncover baseline data and diagnostic information about active control in chronic stroke survivors. Data were collected using sensors during 6 minutes of walking and compared between the paretic and non-paretic legs., Results: The study demonstrated the feasibility of monitoring frontal plane motion and diagnosing disturbed endpoint control ( p  < 0.0125) in chronic stroke survivors when comparing the paretic leg to the non-paretic leg. A greater variability was observed in the paretic leg ( p  < 0.0125), and sensors were able to diagnose a stronger coupling of the body with its endpoint on the paretic side ( p  < 0.0125). Similar results were obtained when monitoring was conducted over a six-minute walking period, and no significant diagnostic differences were found between the two monitoring assessments. Monitoring did not reveal performance fatigue or debilitation over time., Conclusions: This study's findings indicate that monitoring frontal plane motion is a feasible approach for diagnosing compromised walking motion. The results suggest that individuals with walking asymmetries, exhibit differences in endpoint control and variability between their paretic and non-paretic legs. These insights could contribute to more effective rehabilitation strategies and highlight the potential for monitoring compensations during various activities of daily living., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit., Methods: Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available. Central reference histopathology, immunohistochemistry, 850k DNA methylation analysis, gene panel sequencing, and RNA-Seq were performed., Results: FrFr tissue was available in 178/379 enrolled cases. RNA-Seq was performed on 125 of these samples. We confirmed KIAA1549::BRAF-fusion (n = 71), BRAF V600E-mutation (n = 12), and alterations in FGFR1 (n = 14) as the most frequent alterations, among other common molecular drivers (n = 12). N = 16 cases (13%) presented rare gene fusions (eg, TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n = 27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 internal tandem duplications (n = 6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols., Conclusions: The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We propose to include RNA-Seq as part of routine diagnostics for all pLGG patients, especially when no common pLGG alteration was identified., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We examined whether conflicting visual and non-visual information leads to gait abnormalities and how the subthalamic deep brain stimulation (STN DBS) influences gait dysfunction in Parkinson's disease (PD). We used a motion capture system to measure the kinematics of the lower limbs during treadmill walking in immersive virtual reality. The visual information provided in the virtual reality paradigm was modulated to create a mismatch between the optic-flow velocity of the visual scene and the walking speed on the treadmill. In each mismatched condition, we calculated the step duration, step length, step phase, step height, and asymmetries. The key finding of our study was that mismatch between treadmill walking speed and the optic-flow velocity did not consistently alter gait parameters in PD. We also found that STN DBS improved the PD gait pattern by changing the stride length and step height. The effects on phase and left/right asymmetry were not statistically significant. The DBS parameters and location also determined its effects on gait. Statistical effects on stride length and step height were noted when the DBS volume of activated tissue (VTA) was in the dorsal aspect of the subthalamus. The statistically significant effects of STN DBS was present when VTA significantly overlapped with MR tractogrphically measured motor and pre-motor hyperdirect pathways. In summary, our results provide novel insight into ways for controlling walking behavior in PD using STN DBS., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Vibration, a potent mechanical stimulus for activating muscle spindle primary afferents, may improve gait performance in persons with multiple sclerosis (MS), but has yet to be developed and deployed for multiple leg muscles with application during walking training. This study explored the development of a cyclic focal muscle vibration (FMV) system, and the deployment feasibility to correct MS walking swing phase deficits in order to determine whether this intervention warrants comprehensive study. The system was deployed during twelve, two-hour sessions of walking with cyclic FMV over six weeks. Participants served as their own control. Blood pressure, heart rate, walking speed, kinematics (peak hip, knee and ankle angles during swing), toe clearance, and step length were measured before and after deployment with blood pressure and heart rate monitored during deployment. During system deployment, there were no untoward sensations and physiological changes in blood pressure and heart rate, and volitional improvements were found in walking speed, improved swing phase kinematics, toe clearance and step length. This FMV training system was developed and deployed to improve joint flexion during walking in those with MS, and it demonstrated feasibility and benefits. Further study will determine the most effective vibration frequency and dose, carryover effects, and those most likely to benefit from this intervention.

Gait deficits are often persistent after stroke, and current rehabilitation methods do not restore normal gait for everyone. Targeted methods of focused gait therapy that meet the individual needs of each stroke survivor are needed. Our objective was to develop and test a combination protocol of simultaneous brain stimulation and focused stance phase training for people with chronic stroke (>6 months). We combined Transcranial Direct Current Stimulation (tDCS) with targeted stance phase therapy using Virtual Reality (VR)-assisted treadmill training and overground practice. The training was guided by motor learning principles. Five users (>6 months post-stroke with stance phase gait deficits) completed 10 treatment sessions. Each session began with 30 min of VR-assisted treadmill training designed to apply motor learning (ML)-based stance phase targeted practice. During the first 15 min of the treadmill training, bihemispheric tDCS was simultaneously delivered. Immediately after, users completed 30 min of overground (ML)-based gait training. The outcomes included the feasibility of protocol administration, gait speed, Timed Up and Go (TUG), Functional Gait Assessment (FGA), paretic limb stance phase control capability, and the Fugl−Meyer for lower extremity coordination (FMLE). The changes in the outcome measures (except the assessments of stance phase control capability) were calculated as the difference from baseline. Statistically and clinically significant improvements were observed after 10 treatment sessions in gait speed (0.25 ± 0.11 m/s) and FGA (4.55 ± 3.08 points). Statistically significant improvements were observed in TUG (2.36 ± 3.81 s) and FMLE (4.08 ± 1.82 points). A 10-session intervention combining tDCS and ML-based task-specific gait rehabilitation was feasible and produced clinically meaningful improvements in lower limb function in people with chronic gait deficits after stroke. Because only five users tested the new protocol, the results cannot be generalized to the whole population. As a contribution to the field, we developed and tested a protocol combining brain stimulation and ML-based stance phase training for individuals with chronic stance phase deficits after stroke. The protocol was feasible to administer; statistically and/or clinically significant improvements in gait function across an array of gait performance measures were observed with this relatively short treatment protocol.

Mechanical analysis of movement plays an important role in clinical management of neurological and orthopedic conditions. There has been increasing interest in performing movement analysis in real-time, to provide immediate feedback to both therapist and patient. However, such work to date has been limited to single-joint kinematics and kinetics. Here we present a software system, named human body model (HBM), to compute joint kinematics and kinetics for a full body model with 44 degrees of freedom, in real-time, and to estimate length changes and forces in 300 muscle elements. HBM was used to analyze lower extremity function during gait in 12 able-bodied subjects. Processing speed exceeded 120 samples per second on standard PC hardware. Joint angles and moments were consistent within the group, and consistent with other studies in the literature. Estimated muscle force patterns were consistent among subjects and agreed qualitatively with electromyography, to the extent that can be expected from a biomechanical model. The real-time analysis was integrated into the D-Flow system for development of custom real-time feedback applications and into the gait real-time analysis interactive lab system for gait analysis and gait retraining.

Walking is possible for many patients with a spinal cord injury. Avenues enabling walking include braces, robotics and FES. Among the benefits are improved musculoskeletal and mental health, however unrealistic expectations may lead to negative changes in quality of life. Use rigorous assessment standards to gauge the improvement of walking during the rehabilitation process, but also yearly. Continued walking after discharge may be limited by challenges, such as lack of accessibility in and outside the home, and complications, such as shoulder pain or injuries from falls. It is critical to determine the risks and benefits of walking for each patient., (Published by Elsevier Inc.)

The purpose of this single-subject study was to determine the neurotherapeutic and neuroprosthetic effects of an implanted functional electrical stimulation (FES) system designed to facilitate walking in an individual with a longstanding motor and sensory incomplete spinal cord injury. An implanted pulse generator and eight intramuscular stimulating electrodes were installed unilaterally, activating weak or paralyzed hip flexors, hip and knee extensors, and ankle dorsiflexors during 36 sessions of gait training with FES. The neurotherapeutic effects were assessed by a comparison of pre- and posttraining volitional walking. The neuroprosthetic effects were assessed by a comparison of posttraining volitional and FES-assisted walking. Treatment resulted in significant (p < 0.005) volitional improvements in 6-minute walking distance and speed, speed during maximum walk, double support time, and 10 m walking speed. Posttraining FES-assisted walking resulted in significant additional improvements in all these measures, except 10 m walking speed. When the subject was using FES-assisted gait, maximum walking distance, peak knee flexion in swing, peak ankle dorsiflexion in swing, and knee extension moment also significantly increased. Neuroprosthetic gains were sufficient to enable the subject to advance from household ambulation to limited community ambulation. Additionally, the subject could perform multiple walks per day when using FES-assisted gait, which was impossible with volitional effort alone.

Background: The purpose of this study was to determine how a driver's foot and ankle forces during a frontal vehicle collision depend on initial lower extremity posture and brake pedal force., Method of Approach: A 2D musculoskeletal model with seven segments and six right-side muscle groups was used. A simulation of a three-second braking task found 3647 sets of muscle activation levels that resulted in stable braking postures with realistic pedal force. These activation patterns were then used in impact simulations where vehicle deceleration was applied and driver movements and foot and ankle forces were simulated. Peak rearfoot ground reaction force (F(RF)), peak Achilles tendon force (FAT), peak calcaneal force (F(CF)) and peak ankle joint force (F(AJ)) were calculated., Results: Peak forces during the impact simulation were 476 +/- 687 N (F(RF)), 2934 +/- 944 N (F(CF)) and 2449 +/- 918 N (F(AJ)). Many simulations resulted in force levels that could cause fractures. Multivariate quadratic regression determined that the pre-impact brake pedal force (PF), knee angle (KA) and heel distance (HD) explained 72% of the variance in peak FRF, 62% in peak F(CF) and 73% in peak F(AJ)., Conclusions: Foot and ankle forces during a collision depend on initial posture and pedal force. Braking postures with increased knee flexion, while keeping the seat position fixed, are associated with higher foot and ankle forces during a collision.

Muscles have a potentially important effect on lower extremity injuries during an automobile collision. Computational modeling can be a powerful tool to predict these effects and develop protective interventions. Our purpose was to determine how muscles influence peak foot and ankle forces during an automobile collision. A 2-D bilateral musculoskeletal model was constructed with seven segments. Six muscle groups were included in the right lower extremity, each represented by a Hill muscle model. Vehicle deceleration data were applied as input and the resulting movements were simulated. Three models were evaluated: no muscles (NM), minimal muscle activation at a brake pedal force of 400 N (MN), and maximal muscle activation to simulate panic braking (MX). Muscle activation always resulted in large increases in peak joint force. Peak ankle joint force was greatest for MX (10120 N), yet this model also had the lowest peak rearfoot force (629 N). Peak force on the Achilles tendon was 4.5 times greater, during MX (6446 N) compared to MN (1430 N). We conclude that (1). external and internal forces are dependent on muscles, (2). muscle activation level could exacerbate axial loading injuries, (3). external and internal forces can be inversely related once muscle properties are included.

The purpose of this study was to investigate the influence of midsole durometer on mechanical and hematological responses during a prolonged downhill run. Twenty-four men completed a 30-min downhill run (-12% grade) wearing either soft, medium, or hard midsole shoes. Data describing mean peak tibial acceleration (PTA), stride frequency, plasma free hemoglobin, hemoglobin concentration, hematocrit, and creatine kinase (CK) were collected. While there were no significant differences in PTA among midsole durometer shoes, PTA increased by 20% after the first 5 min of the run over all other time intervals during the run (p < .05). Hemolysis showed a 50.2% increase from prerun to postrun values (p <.05). CK increased from the prerun state to 24 hr after the run (p <. 05). Downhill running, irrespective of midsole durometer, showed increased levels of legshock, hemolysis, and muscle damage over values that are present in the literature for a level running protocol.