Manipulating post-stroke gait: Exploiting aberrant kinematics

Post-stroke individuals often exhibit abnormal kinematics, including increased pelvic obliquity and hip abduction coupled with reduced knee flexion. Prior examinations suggest these behaviors are expressions of abnormal cross-planar coupling of muscle activity. However, few studies have detailed the impact of gait-retraining paradigms on three-dimensional joint kinematics. In this study, a cross-tilt walking surface was examined as a novel gait-retraining construct. We hypothesized that relative to baseline walking kinematics, exposure to cross-tilt would generate significant changes in subsequent flat-walking joint kinematics during affected limb swing. Twelve post-stroke participants walked on a motorized treadmill platform during a flat-walking condition and during a 10-degree cross-tilt with affected limb up-slope, increasing toe clearance demand. Individuals completed 15 min of cross-tilt walking with intermittent flat-walking catch trials and a final washout period (5 min). For flat-walking conditions, we examined changes in pelvic obliquity, hip abduction/adduction and knee flexion kinematics at the spatiotemporal events of swing initiation and toe-off, and the kinematic event of maximum angle during swing. Pelvic obliquity significantly reduced at swing initiation and maximum obliquity in the final catch trial and late washout. Knee flexion significantly increased at swing initiation, toe-off, and maximum flexion across catch trials and late washout. Hip abduction/adduction was not significantly influenced following cross-tilt walking. Significant decrease in the rectus femoris and medial hamstrings muscle activity across catch trials and late washout was observed. Exploiting the abnormal features of post-stroke gait during retraining yielded desirable changes in muscular and kinematic patterns post-training.     

Proximal gait adaptations in individuals with knee osteoarthritis: A systematic review and meta-analysis

Clarifying proximal gait adaptations as a strategy to reduce knee joint loading and pain for individuals with knee osteoarthritis (OA) contributes to understanding the pathogenesis of multi-articular OA changes and musculoskeletal pain in other joints. We aimed to determine whether biomechanical alterations in knee OA patients during level walking is increased upper trunk lean in the frontal and sagittal planes, and subsequent alteration in external hip adduction moment (EHAM) and external hip flexion moment (EHFM). A literature search was conducted in PubMed, PEDro, CINAHL, and Cochrane CENTRAL through May 2018. Where possible, data were combined into a meta-analysis; pooled standardized mean differences (SMD) of between knee OA patients and healthy adults were calculated using a random-effect model. In total, 32 articles (2037 participants, mean age, 63.0 years) met inclusion criteria. Individuals with knee OA had significantly increased lateral trunk lean toward the ipsilateral limb (pooled SMD: 1.18; 95% CI: 0.59, 1.77) along with significantly decreased EHAM. These subjects also displayed a non-significantly increased trunk/pelvic flexion angle and EHFM. The GRADE approach judged all measures as “very low.” These results may indicate that biomechanical alterations accompanying knee OA are associated with increased lateral trunk lean and ensuing alterations in EHAM. Biomechanical alterations in the sagittal plane were not evident. Biomechanical adaptations might have negative sequelae, such as secondary hip abductor muscle weakness and low back pain. Thus, investigations of negative sequelae due to proximal gait adaptations are warranted.     

Minimum toe clearance adaptations to floor surface irregularity and gait speed

Toe speed during gait generally nears its maximum while its height reaches a local minima approximately halfway through swing phase. Trips are thought to frequently occur at these local minima (minimum toe clearance or MTC events) and trip risk has been quantified using the minimum distance between the toe and ground here (MTC). This study investigated MTC on floor surfaces with and without multiple small obstacles. After shoes and floor surfaces were digitized, 14 unimpaired subjects (half women) each traversed a 4.88 m walkway 4 times at slow, preferred, and fast speeds across surfaces with no obstacles, visible obstacles, and hidden obstacles. Both surfaces with obstacles had the same random obstacle configuration. Shoe and body segment motions were tracked using passive markers and MTC and joint kinematics calculated. All MTC and kinematic variables tested significantly increased with faster instructed gait speed except the likelihood of MTC event occurrence (local minima in minimum toe clearance trajectory when foot is in upper quartile of speed). MTC events were less frequent for swing phases on surfaces with obstacles (80% vs. 98% for no obstacles). MTC values, when present, were doubled by the presence of visible obstacles (22.2 ± 7.3mm vs. 11.1 ± 5.7 mm) and further increased to 26.8 ± 7.1mm when these obstacles were hidden from view (all comparisons p ≤ 0.0003). These substantial floor surface-related changes in MTC event occurrences and values resulted from alterations in toe- and heel-clearance trajectories caused by subtle but significant changes in joint kinematics that did not exceed 10% each joint's swing phase range of motion.     

Biomechanical gait analysis of pigs walking on solid concrete floor

Inappropriate floors in pig pens and slippery floor conditions may cause leg problems that reduce animal welfare. Therefore the objectives of the present study were to characterise the walk of pigs on dry concrete solid floor, to evaluate whether pigs modify their gait according to floor condition, and to suggest a coefficient of friction (COF) that ensures safe walking on solid concrete floors for pigs. Kinematic (50 Hz video recordings in the sagittal plane) and kinetic (1 KHz force plate measuring three perpendicular ground reaction forces) data were collected from four strides of both the fore- and hindlimbs of 30 healthy pigs walking on dry, greasy and wet concrete floor with 10 pigs on each floor condition. The COF of the floor conditions were tested in a drag-test. The results from the gait analysis showed that the pigs adapted their gait to potentially slippery floors by lowering their walking speed and reducing their peak utilised COF on greasy and wet (contaminated) floors compared with dry floors. Moreover, the pigs shortened their progression length and prolonged their stance phase duration on greasy floor compared with dry and wet floors. Thus the greasy floor appeared the most slippery condition to the pigs, whereas the wet floor was intermediate to the other two conditions. The pigs walked with a four-beat gait, and the limbs differed biomechanically, as the forelimbs carried more load, received higher peak vertical forces and had longer lasting stance phases than did the hindlimbs. The utilised COF from the gait analysis indicated that a high floor COF (>0.63) is needed to prevent pigs from slipping and thus to ensure safe walking on dry concrete floors.     

Muscle contributions to support during gait in an individual with post-stroke hemiparesis

Walking requires coordination of muscles to support the body during single stance. Impaired ability to coordinate muscles following stroke frequently compromises walking performance and results in extremely low walking speeds. Slow gait in post-stroke hemiparesis is further complicated by asymmetries in lower limb muscle excitations. The objectives of the current study were: (1) to compare the muscle coordination patterns of an individual with flexed stance limb posture secondary to post-stroke hemiparesis with that of healthy adults walking very slowly, and (2) to identify how paretic and non-paretic muscles provide support of the body center of mass in this individual. Simulations were generated based on the kinematics and kinetics of a stroke survivor walking at his self-selected speed (0.3 m/s) and of three speed-matched, healthy older individuals. For each simulation, muscle forces were perturbed to determine the muscles contributing most to body weight support (i.e., height of the center of mass during midstance). Differences in muscle excitations and midstance body configuration caused paretic and non-paretic ankle plantarflexors to contribute less to midstance support than in healthy slow gait. Excitation of paretic ankle dorsiflexors and knee flexors during stance opposed support and necessitated compensation by knee and hip extensors. During gait for an individual with post-stroke hemiparesis, adequate body weight support is provided via reorganized muscle coordination patterns of the paretic and non-paretic lower limbs relative to healthy slow gait.     

Biomechanical mechanism of lateral trunk lean gait for knee osteoarthritis patients

The biomechanical mechanism of lateral trunk lean gait employed to reduce external knee adduction moment (KAM) for knee osteoarthritis (OA) patients is not well known. This mechanism may relate to the center of mass (COM) motion. Moreover, lateral trunk lean gait may affect motor control of the COM displacement. Uncontrolled manifold (UCM) analysis is an evaluation index used to understand motor control and variability of the motor task. Here we aimed to clarify the biomechanical mechanism to reduce KAM during lateral trunk lean gait and how motor variability controls the COM displacement. Twenty knee OA patients walked under two conditions: normal and lateral trunk lean gait conditions. UCM analysis was performed with respect to the COM displacement in the frontal plane. We also determined how the variability is structured with regards to the COM displacement as a performance variable. The peak KAM under lateral trunk lean gait was lower than that under normal gait. The reduced peak KAM observed was accompanied by medially shifted knee joint center, shortened distance of the center of pressure to knee joint center, and shortened distance of the knee–ground reaction force lever arm during the stance phase. Knee OA patients with lateral trunk lean gait could maintain kinematic synergy by utilizing greater segmental configuration variance to the performance variable. However, the COM displacement variability of lateral trunk lean gait was larger than that of normal gait. Our findings may provide clinical insights to effectively evaluate and prescribe gait modification training for knee OA patients.     

Biomechanical adaptations for burrowing in the incisor enamel microstructure of Geomyidae and Heteromyidae (Rodentia: Geomyoidea)

The enamel microstructure of fossil and extant Geomyoidea (Geomyidae, Heteromyidae) lower incisors incorporates three‐ or two‐layered schmelzmusters with uniserial, transverse Hunter‐Schreger bands having parallel and perpendicular or exclusively perpendicular oriented interprismatic matrix. Phylogenetically, these schmelzmusters are regarded as moderately (enamel type 2) to highly derived (enamel type 3). Our analysis detected a zone of modified radial enamel close to the enamel–dentine junction. Modified radial enamel shows a strong phylogenetic signal within the clade Geomorpha as it is restricted to fossil and extant Geomyoidea and absent in Heliscomyidae, Florentiamyidae, and Eomyidae. This character dates back to at least the early Oligocene (early Arikareean, 29 Ma), where it occurs in entoptychine gophers. We contend that this specialized incisor enamel architecture developed as a biomechanical adaptation to regular burrowing activities including chisel‐tooth digging and a fiber‐rich diet and was probably present in the common ancestor of the clade. We regard the occurrence of modified radial enamel in lower incisors of scratch‐digging Geomyidae and Heteromyidae as the retention of a plesiomorphic character that is selectively neutral. The shared occurrence of modified radial enamel is a strong, genetically anchored argument for the close phylogenetic relationship of Geomyidae and Heteromyidae on the dental microstructure level.     

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes – processing speed, whole‐brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3′ untranslated region of voltage‐gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.     

Post-opioid receptor adaptations to chronic morphine; altered functionality and associations of signaling molecules

Opioid desensitization/tolerance mechanisms have largely focused on adaptations that occur on the level of the mu-opioid receptor (MOR) itself. These include opioid receptor phosphorylation and ensuing trafficking events. Recent research, however, has revealed additional adaptations that occur downstream from the opioid receptor, which involve covalent modification of signaling molecules and altered associations among them. These include augmented isoform-specific synthesis of adenylyl cyclase (AC) and their phosphorylation as well as augmented phosphorylation of the G(beta) subunit of G(beta gamma). The aggregate effect of these changes is to shift mu-opioid receptor-coupled signaling from predominantly G(i alpha) inhibitory to (G(i)-derived) G(beta gamma) stimulatory AC signaling. Most recently, chronic morphine has been shown to enhance the association (interaction) between MOR and G(s), which should provide an additional avenue for offsetting inhibitory MOR signaling sequelae. The unfolding complexity of chronic morphine-induced sequelae demands an evolving broader and more encompassing perspective on opioid tolerance-producing mechanisms. This should facilitate understanding tolerance within the context of physiological plasticity that is activated by chronic exposure to drugs of abuse. Additional research is required to integrate the various tolerance-producing adaptations that have been elucidated to date. Specifically, the relative contribution to opioid tolerance of identified adaptations is still unknown as is the extent to which they vary among different regions of the central nervous system.     

Reliability and comparison of Kinect-based methods for estimating spatiotemporal gait parameters of healthy and post-stroke individuals

Different studies have analyzed the potential of the off-the-shelf Microsoft Kinect, in its different versions, to estimate spatiotemporal gait parameters as a portable markerless low-cost alternative to laboratory grade systems. However, variability in populations, measures, and methodologies prevents accurate comparison of the results. The objective of this study was to determine and compare the reliability of the existing Kinect-based methods to estimate spatiotemporal gait parameters in healthy and post-stroke adults. Forty-five healthy individuals and thirty-eight stroke survivors participated in this study. Participants walked five meters at a comfortable speed and their spatiotemporal gait parameters were estimated from the data retrieved by a Kinect v2, using the most common methods in the literature, and by visual inspection of the videotaped performance. Errors between both estimations were computed. For both healthy and post-stroke participants, highest accuracy was obtained when using the speed of the ankles to estimate gait speed (3.6–5.5 cm/s), stride length (2.5–5.5 cm), and stride time (about 45 ms), and when using the distance between the sacrum and the ankles and toes to estimate double support time (about 65 ms) and swing time (60–90 ms). Although the accuracy of these methods is limited, these measures could occasionally complement traditional tools.     

Biomechanical analysis of the three-dimensional foot structure during gait: a basic tool for clinical applications

A novel three-dimensional numerical model of the foot, incorporating, for the first time in the literature, realistic geometric and material properties of both skeletal and soft tissue components of the foot, was developed for biomechanical analysis of its structural behavior during gait. A system of experimental methods, integrating the optical Contact Pressure Display (CPD) method for plantar pressure measurements and a Digital Radiographic Fluoroscopy (DRF) instrument for acquisition of skeletal motion during gait, was also developed in this study and subsequently used to build the foot model and validate its predictions. Using a Finite Element solver, the stress distribution within the foot structure was obtained and regions of elevated stresses for six subphases of the stance (initial-contact, heel-strike, midstance, forefoot-contact, push-off, and toe-off) were located. For each of these subphases, the model was adapted according to the corresponding fluoroscopic data, skeletal dynamics, and active muscle force loading. Validation of the stress state was achieved by comparing model predictions of contact stress distribution with respective CPD measurements. The presently developed measurement and numerical analysis tools open new approaches for clinical applications, from simulation of the development mechanisms of common foot disorders to pre- and post-interventional evaluation of their treatment.     

Strong independent associations between gait biomechanics and pain in patients with knee osteoarthritis

We investigated the simple and multivariate associations between knee pain and gait biomechanics. 279 patients with medial knee osteoarthritis (OA) and discordant changes in pain between limbs after walking completed bilateral three-dimensional gait analysis. For each limb, patients rated their pain before and after a 6-min walk and the change in pain was recorded as an increase (≥1 points) or not (≤0 points). Among paired limbs, the simple and multivariate associations between an increase in pain and the external moments in each orthogonal plane were evaluated using conditional logistic regression. The analyses were then repeated for knee angles. Univariate analyses demonstrated associations in each plane that varied in both magnitude and direction, with larger associations for the knee moments [Odds Ratio (95% confidence interval) = first peak adduction moment: 2.80 (2.02, 3.88), second peak adduction moment: 2.36 (1.73, 3.24), adduction impulse: 6.65 (3.50, 12.62), flexion moment: 0.46 (0.36, 0.60), extension moment: 0.56 (0.44, 0.71), internal rotation moment: 7.54 (3.32, 17.13), external rotation moment: 0.001 (0.00, 0.04)]. Multivariate analyses with backward elimination resulted in a model including only the adduction impulse [5.35 (2.51, 11.42)], flexion moment [0.32 (0.22, 0.46)] and extension moment [0.28 (0.19, 0.42)]. The varus, flexion and extension angles were included in the final multivariate model for the knee angles. When between-person confounding is lessened by comparing limbs within patients, there are strong independent associations between knee pain and multiple external knee moments that vary in magnitude and direction. While controlling for other knee moments, a greater adduction impulse and lower flexion and extension moments were independently associated with greater odds of an increase in pain.     

Preoperative gait adaptations persist one year after surgery in clinically well-functioning total hip replacement patients

The purpose of this study was to evaluate whether preoperative gait adaptations persist one year after THR in the same set of subjects. The hypothesis tested was that hip dynamic range of motion and peak external moments during walking return to normal after THR. Hip kinematics and kinetics were measured for 28 subjects before and one year after THR and compared to those of 25 subjects with radiographically normal hips. All THR subjects improved clinically after surgery with Harris hip scores improving from 33-85 (average 53) to 61-100 (average 95) (sign test p<0.001). Preoperatively dynamic hip range of motion (ROM), and all peak external moments were reduced compared to normal (Mann-Whitney p< or =0.040). Improvement was seen in the ROM and all but the frontal plane, and external rotation peak moments (Friedman p< or =0.023). The preoperative and postoperative values of the ROM, and peak flexion, abduction and external rotation moments were all significantly correlated (Spearman p<0.020) indicating a possible learned effect from before THR surgery. Postoperative THR subjects continued to have a significantly lower than normal ROM, and peak adduction and peak internal rotation moments (Mann-Whitney p< or =0.003). Despite good to excellent clinical functional outcome, gait in THR patients does not return to normal by one year after surgery. Aggressive muscle strengthening is currently not emphasized after THR surgery. Some THR patients may benefit from more intensive rehabilitation before and after surgery.     

Effect of plantarflexion resistance of an ankle-foot orthosis on ankle and knee joint power during gait in individuals post-stroke

Plantarflexion resistance of an ankle-foot orthosis (AFO) plays an important role to prevent foot-drop, but its impact on push-off has not been well investigated in individuals post-stroke. The aim of this study was to investigate the effect of plantarflexion resistance of an articulated AFO on ankle and knee joint power of the limb wearing the AFO in individuals post-stroke. Gait analysis was performed on 10 individuals with chronic stroke using a Vicon 3-dimensional motion capture system and a Bertec split-belt instrumented treadmill. They walked on the treadmill under 4 plantarflexion resistance levels (S1 < S2<S3 < S4) set on the AFO with resistance adjustable ankle joints. The ankle and knee joint power calculations were performed using Visual3D, and mean values were plotted across a gait cycle. Statistical analyses revealed significant differences in the peak ankle joint power generation according to the plantarflexion resistance of the AFO (P = 0.008). No significant differences were found in the knee joint power. Peak ankle joint power generation [Median (IQR: Interquartile range)] were S1: 0.0517 (0.0238–0.1071) W/kg, S2: 0.0342 (0.0132–0.0862) W/kg, S3: 0.0353 (0.0127–0.0821) W/kg, and S4: 0.0234 (0.0087–0.06764) W/kg. Reduction of the peak ankle joint power generation appeared to be related to reduction in the peak plantarflexion angular velocity at late stance due to increases in the plantarflexion resistance of the AFO. This study showed that peak ankle joint power generation was significantly, and somewhat systematically, affected by plantarflexion resistance of the AFO in individuals post-stroke.     

Pharmacological treatment of intermittent claudication does not have a significant effect on gait impairments during claudication pain

Peripheral arterial disease (PAD) is a manifestation of atherosclerosis resulting in intermittent claudication (IC) or leg pain during physical activity. Two drugs (cilostazol and pentoxifylline) are approved for treatment of IC. Our previous work has reported no significant differences in gait biomechanics before and after drug interventions when PAD patients walked without pain. However, it is possible that the drugs are more efficacious during gait with pain. Our aim was to use advanced biomechanical analysis to evaluate the effectiveness of these drugs while walking with pain. Initial and absolute claudication distances, joint kinematics, torques, powers, and gait velocity during the presence of pain were measured from 24 patients before and after 12 weeks of treatment with either cilostazol or pentoxifylline. We found no significant improvements after 12 weeks of treatment with either cilostazol or pentoxifylline on the gait biomechanics of PAD patients during pain. Our findings indicate that the medications cilostazol and pentoxifylline have reduced relevance in the care of gait dysfunction even during pain in patients with PAD.     

Autophagosome formation: core machinery and adaptations

Eukaryotic cells employ autophagy to degrade damaged or obsolete organelles and proteins. Central to this process is the formation of autophagosomes, double-membrane vesicles responsible for delivering cytoplasmic material to lysosomes. In the past decade many autophagy-related genes, ATG, have been identified that are required for selective and/or nonselective autophagic functions. In all types of autophagy, a core molecular machinery has a critical role in forming sequestering vesicles, the autophagosome, which is the hallmark morphological feature of this dynamic process. Additional components allow autophagy to adapt to the changing needs of the cell.