High tibial osteotomy results in improved frontal plane knee moments, gait patterns and patient-reported outcomes.

PURPOSE: The purpose of this study was to quantify changes in knee loading in the three clinical planes, compensatory gait adaptations and patient-reported outcome measures (PROMS) resulting from opening wedge high tibial osteotomy (HTO). METHODS: Gait analysis was performed on 18 participants (19 knees) with medial osteoarthritis (OA) and varus alignment pre- and post-HTO, along with 18 controls, to calculate temporal, kinematic and kinetic measures. Oxford Knee Score, Knee Outcome Survey and visual analogue pain scores were collected. Paired and independent sample tests identified changes following surgery and deviations from controls. RESULTS: HTO restored frontal and transverse plane knee joint loading to that of the control group, while reductions remained in the sagittal plane. Elevated frontal plane trunk sway (p = 0.031) and reduced gait speed (p = 0.042), adopted as compensatory gait changes pre-HTO, were corrected by the surgery. PROMs significantly improved (p ≤ 0.002). Centre of pressure (COP) was lateralised relative to the knee post-HTO (p < 0.001). Energy absorbed in the sagittal plane significantly increased post-HTO (p = 0.007), whilst work done in the transverse plane reduced (p ≤ 0.008). Pre-operative gait deviations from the control group that were retained post-HTO included smaller sagittal (p = 0.003) knee range of motion during gait, greater stance duration (p = 0.008) and altered COP location (anterior to the knee) in early stance (p = 0.025). CONCLUSIONS: HTO surgery restored frontal and transverse plane knee loading to normal levels and improved PROMs. Gait adaptations known to reduce knee loading employed pre-HTO were not retained post-HTO. Some gait features were found to differ between post-HTO subjects and controls. LEVEL OF EVIDENCE: II.

Small diameter helical vascular scaffolds support endothelial cell survival.

There is an acute clinical need for small-diameter vascular grafts as a treatment option for cardiovascular disease. Here, we used an intelligent design system to recreate the natural structure and hemodynamics of small arteries. Nano-fibrous tubular scaffolds were fabricated from blends of polyvinyl alcohol and gelatin with inner helices to allow a near physiological spiral flow profile, using the electrospinning technique. Human coronary artery endothelial cells (ECs) were seeded on the inner surface and their viability, distribution, gene expression of mechanosensitive and adhesion molecules compared to that in conventional scaffolds, under static and flow conditions. We show significant improvement in cell distribution in helical vs. conventional scaffolds (94% ±â€¯9% vs. 82% ±â€¯7.2%; P < 0.05) with improved responsiveness to shear stress and better ability to withhold physiological pressures. Our helical vascular scaffold provides an improved niche for EC growth and may be attractive as a potential small diameter vascular graft.

Harmonising data collection from osteoarthritis studies to enable stratification: recommendations on core data collection from an Arthritis Research UK clinical studies group.

OBJECTIVE: Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies. METHODS: An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies. RESULTS: Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above. CONCLUSIONS: Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment.

Recommendations for the conduct of efficacy trials of treatment devices for osteoarthritis: a report from a working group of the Arthritis Research UK Osteoarthritis and Crystal Diseases Clinical Studies Group.

OBJECTIVE: There are unique challenges to designing and carrying out high-quality trials testing therapeutic devices in OA and other rheumatic diseases. Such challenges include determining the mechanisms of action of the device and the appropriate sham. Design of device trials is more challenging than that of placebo-controlled drug trials. Our aim was to develop recommendations for designing device trials. METHODS: An Arthritis Research UK study group comprised of 30 rheumatologists, physiotherapists, podiatrists, engineers, orthopaedists, trialists and patients, including many who have carried out device trials, met and (using a Delphi-styled approach) came to consensus on recommendations for device trials. RESULTS: Challenges unique to device trials include defining the mechanism of action of the device and, therefore, the appropriate sham that provides a placebo effect without duplicating the action of the active device. Should there be no clear-cut mechanism of action, a three-arm trial including a no-treatment arm and one with presumed sham action was recommended. For individualized devices, generalizable indications and standardization of the devices are needed so that treatments can be generalized. CONCLUSION: A consensus set of recommendations for device trials was developed, providing a basis for improved trial design, and hopefully improvement in the number of effective therapeutic devices for rheumatic diseases.

Utilising electrodermal activity sensor signals to quantify nociceptive response during movement activities.

OBJECTIVE: With an increasingly ageing population and osteoarthritis prevalence, the quantification of nociceptive signals responsible for painful movements and individual responses could lead to better treatment and monitoring solutions. Changes in electrodermal activity (EDA) can be detected via changes in skin conductance (SC) and measured using finger electrodes on a wearable sensor, providing objective information for increased physiological stress response. RESULTS: To provide EDA response preliminary data, this was recorded with healthy volunteers on an array of activities while receiving a noxious stimulus. This provides a defined scenario that can be utilised as protocol feasibility testing. Raw signal extraction, processing and statistical analysis was performed using mean SC values on all participant data. The application of the stimuli resulted in a significant average increase (p < 0.05) in mean SC in four out of five activities with significant gender differences (p < 0.05) in SC and self-reported pain scores and large effect sizes. Though EDA parameters are a promising tool for nociceptive response indicators, limitations including motion artifact sensitivities and lack of previous movement-based EDA published data result in restricted analysis understanding. Refined processing pipelines with signal decomposition tools could be utilised in a protocol that quantifies nociceptive response clinically meaningfully.

A 3D motion analysis study comparing the effectiveness of cervical spine orthoses at restricting spinal motion through physiological ranges.

OBJECTIVE: To compare the effectiveness of the Aspen, Aspen Vista, Philadelphia, Miami-J and Miami-J Advanced collars at restricting cervical spine movement in the sagittal, coronal and axial planes. METHODS: Nineteen healthy volunteers (12 female, 7 male) were recruited to the study. Collars were fitted by an approved physiotherapist. Eight ProReflex (Qualisys, Sweden) infrared cameras were used to track the movement of retro-reflective marker clusters placed in predetermined positions on the head and trunk. 3D kinematic data were collected during forward flexion, extension, lateral bending and axial rotation from uncollared to collared subjects. The physiological range of motion in the three planes was analysed using the Qualisys Track Manager System. RESULTS: The Aspen and Philadelphia were significantly more effective at restricting flexion/extension than the Vista (p < 0.001), Miami-J (p < 0.001 and p < 0.01) and Miami-J Advanced (p < 0.01 and p < 0.05). The Aspen was significantly more effective at restricting rotation than the Vista (p < 0.001) and the Miami-J (p < 0.05). The Vista was significantly the least effective collar at restricting lateral bending (p < 0.001). CONCLUSION: Our motion analysis study found the Aspen collar to be superior to the other collars when measuring restriction of movement of the cervical spine in all planes, particularly the sagittal and transverse planes, while the Aspen Vista was the least effective collar.

Using musculoskeletal modelling to estimate knee joint loading pre and post high tibial osteotomy.

BACKGROUND: Both medial knee osteoarthritis and associated varus alignment have been proposed to alter knee joint loading and consequently overloading the medial compartment. Individuals with knee osteoarthritis and varus deformity are candidates for coronal plane corrective surgery, high tibial osteotomy. This study evaluated knee loading and contact location for a control group, a pre-surgery cohort and the same cohort 12 months post-surgery using a musculoskeletal modelling approach. METHODS: Joint kinematics during gait were measured in 30 knee osteoarthritis patients, before and after high tibial osteotomy, and 28 healthy adults. Using a musculoskeletal model that incorporated patient-specific mechanical tibial femoral angle, the resulting muscle, ligament, and contact forces were calculated and the medial - lateral condyle load distribution was analysed. FINDINGS: Surgery changed medial compartment contact force throughout stance relative to pre-surgery. This reduction in medial compartment contact force pre- vs post-HTO is observed despite a significant increase in post-surgery walking speed compared to pre-HTO, where increased speed is typically associated with increased joint loading. INTERPRETATION: This study has estimated the effects of high tibial osteotomy on knee loading using a generic model that incorporates a detailed knee model to better understand tibiofemoral contact loading. The findings support the aim of surgery to unload the medial knee compartment and lateralise joint contact forces.

Biomechanics beyond the lab: Remote technology for osteoarthritis patient data-A scoping review.

The objective of this project is to produce a review of available and validated technologies suitable for gathering biomechanical and functional research data in patients with osteoarthritis (OA), outside of a traditionally fixed laboratory setting. A scoping review was conducted using defined search terms across three databases (Scopus, Ovid MEDLINE, and PEDro), and additional sources of information from grey literature were added. One author carried out an initial title and abstract review, and two authors independently completed full-text screenings. Out of the total 5,164 articles screened, 75 were included based on inclusion criteria covering a range of technologies in articles published from 2015. These were subsequently categorised by technology type, parameters measured, level of remoteness, and a separate table of commercially available systems. The results concluded that from the growing number of available and emerging technologies, there is a well-established range in use and further in development. Of particular note are the wide-ranging available inertial measurement unit systems and the breadth of technology available to record basic gait spatiotemporal measures with highly beneficial and informative functional outputs. With the majority of technologies categorised as suitable for part-remote use, the number of technologies that are usable and fully remote is rare and they usually employ smartphone software to enable this. With many systems being developed for camera-based technology, such technology is likely to increase in usability and availability as computational models are being developed with increased sensitivities to recognise patterns of movement, enabling data collection in the wider environment and reducing costs and creating a better understanding of OA patient biomechanical and functional movement data.

Knee osteoarthritis alters peri-articular knee muscle strategies during gait.

The primary role of muscles is to move, and control joints. It is therefore important to understand how degenerative joint disease changes this role with the resulting effect on mechanical joint loading. Muscular control strategies can vary depending on strength and coordination which in turn influences joint control and loading. The purpose of this study was to investigate the variation in neuromuscular control mechanisms and joint biomechanics for three subject groups including those with: uni-compartmental knee osteoarthritis (OA), listed for high tibial osteotomy surgery (pre-HTO, n = 10); multi-compartmental knee OA listed for total knee replacement (pre-TKR, n = 9), and non-pathological knees (NP, n = 11). Lower limb kinematics and electromyography (EMG) data for subjects walking at self-selected speed, were input to an EMG-driven musculoskeletal knee model which was scaled and calibrated to each individual to estimate muscle forces. Compared to NP, the peak gastrocnemius muscle force reduced by 30% and 18% for pre-HTO and pre-TKR respectively, and the peak force estimated for hamstring muscle increased by 25% for pre-HTO. Higher quadriceps and hamstring forces suggest that co-contraction with the gastrocnemius could lead to higher joint contact forces. Combined with the excessive loading due to a high external knee adduction moment this may exacerbate joint destruction. An increased lateral muscle co-contraction reflects the progression from NP to uni-compartmental OA (pre-HTO). Pre-TKR patients adopt a different gait pattern to pre-HTO patients. Increased medial muscle co-activation could potentially differentiate between uni- or multi-compartmental OA.

Gait function improvements, using Cardiff Classifier, are related to patient-reported function and pain following hip arthroplasty.

Summarizing results of three-dimensional (3D) gait analysis into a comprehensive measure of overall gait function is valuable to discern to what extent gait function is affected, and later recovered after surgery and rehabilitation. This study aimed to investigate whether preoperative gait function, quantified and summarized using the Cardiff Classifier, can predict improvements in postoperative patient-reported activities of daily living, and overall gait function 1 year after total hip arthroplasty (THA). Secondly, to explore relationships between pre-to-post surgical change in gait function versus changes in patient-reported and performance-based function. Thirty-two patients scheduled for THA and 25 nonpathological individuals were included in this prospective cohort study. Patients were evaluated before THA and 1 year postoperatively using 3D gait analysis, patient-reported outcomes, and performance-based tests. Kinematic and kinetic gait parameters, derived from 3D gait analysis, were quantified using the Cardiff Classifier. Linear regressions investigated the predictive value of preoperative gait function on postoperative outcomes of function, and univariate correlations explored relationships between pre-to-post surgical changes in outcome measures. Preoperative gait function, by means of Cardiff Classifier, explained 35% and 30% of the total variance in change in patient-reported activities of daily living, and in gait function, respectively. Moderate-to-strong correlations were found between change in gait function and change in patient-reported function and pain, while no correlations were found between change in gait function and performance-based function. Clinical significance: Preoperative gait function predicts postsurgical function to a moderate degree, while improvements in gait function after surgery are more closely related to how patients perceive function than their maximal performance of functional tests.

Data sharing across osteoarthritis research groups and disciplines: Opportunities and challenges.

Background: Osteoarthritis is a heterogeneous condition characterised by a wide variety of factors and represents a worldwide healthcare challenge. There are multiple clinical and research specialisms involved in the diagnosis, prognosis and treatment of osteoarthritis, and there may be opportunities to share or pool data which are currently not being utilised. However, there are challenges to doing so which require carefully structured solutions and partnership working. Methods: Interviews were conducted with nine experts from various fields within osteoarthritis research. A semi-structured approach was used, and thematic analysis applied to the results. Results: Generally, osteoarthritis researchers were supportive of data sharing, provided it is done responsibly and without impacting data integrity. Benefits identified included increasing typically low-powered data, the potential for machine learning opportunities, and the potential for improved patient outcomes. However, a number of challenges were identified, relating to: data security, data harmonisation, storage costs, ethical considerations and governance. Conclusions: There is clear support for increased data sharing and partnership working in osteoarthritis research. Further investigation will be required to navigate the complex issues identified; however, it is clear that collaborative opportunities should be better facilitated and there may be innovative ways to do this. It is also clear that nomenclature within different disciplines could be better streamlined, to improve existing opportunities to harmonise data.

Alternative radiopacifiers for polymethyl methacrylate bone cements: Silane-treated anatase titanium dioxide and yttria-stabilised zirconium dioxide.

Poly (methyl methacrylate) (PMMA) bone cement is widely used for anchoring joint arthroplasties. In cement brands approved for these procedures, micron-sized particles (usually barium sulphate, BaSO4) act as the radiopacifier. It has been postulated that these particles act as sites for crack initiation and subsequently cement fatigue. This study investigated whether alternative radiopacifiers, anatase titanium dioxide (TiO2) and yttria-stabilised zirconium dioxide (ZrO2), could improve the in vitro mechanical, fatigue crack propagation and biological properties of polymethyl methacrylate (PMMA) bone cement and whether their coating with a silane could further enhance cement performance. Cement samples containing 0, 5, 10, 15, 20 and 25%w/w TiO2 or ZrO2 and 10%w/w silane-treated TiO2 or ZrO2 were prepared and characterised in vitro in terms of radiopacity, compressive and bending strength, bending modulus, fatigue crack propagation, hydroxyapatite forming ability and MC3T3-E1 cell attachment and viability. Cement samples with greater than 10%w/w TiO2 and ZrO2 had a similar radiopacity to the control 10%w/w BaSO4 cement and commercial products. The addition of TiO2 and ZrO2 to bone cement reduced the bending strength and fracture toughness and increased fatigue crack propagation due to the formation of agglomerations and voids. Silane treating TiO2 reversed this effect, enhancing the dispersion and adhesion of particles to the PMMA matrix and resulted in improved mechanical properties and fatigue crack propagation resistance. Silane-treated TiO2 cements had increased nucleation of hydroxyapatite and MC3T3-E1 cell attachment in vitro, without significantly compromising cell viability. This research has demonstrated that 10%w/w silane-treated anatase TiO2 is a promising alternative radiopacifier for PMMA bone cement offering additional benefits over conventional BaSO4 radiopacifiers.

The relationship between alignment, function and loading in total knee replacement: In-vivo analysis of a unique patient population.

The purpose of this study was to quantify the effect of total knee replacement (TKR) alignment on in-vivo knee function and loading in a unique patient cohort who have been identified as having a high rate of component mal-alignment. Post-TKR (82.4 ± 6.7 months), gait analysis was performed on 25 patients (27 knees), to calculate knee kinematics and kinetics. For a step activity, video fluoroscopic analysis quantified in-vivo implant kinematics. Frontal plane lower-limb alignment was defined by the Hip-Knee-Ankle angle (HKA) measured on long leg static X-rays. Transverse plane component rotation was calculated from computed tomography scans. Sagittal plane alignment was defined by measuring the flexion angle of the femoral component and the posterior tibial slope angle (PTSA). For gait analysis, a more varus HKA correlated with increased peak and dynamic joint kinetics, predicting 47.6% of Knee Adduction Angular Impulse variance. For the step activity, during step-up and single leg loaded, higher PTSA correlated with a posterior shift in medial compartment Anterior-Posterior (AP) translation. During step-down, higher PTSA correlated with reduced lateral compartment AP translation with a posterior shift in AP translation in both compartments. A more varus HKA correlated with a more posterior medial AP translation and inter-component rotation was related to transverse plan range of motion. This in-vivo study found that frontal plane lower-limb alignment had a significant effect on joint forces during gait but had minimal influence on in-vivo implant kinematics for step activity. PTSA was found to influence in-vivo TKR translations and is therefore an important surgical factor.

The use of technology in the subcategorisation of osteoarthritis: a Delphi study approach.

Objective: This UK-wide OATech Network + consensus study utilised a Delphi approach to discern levels of awareness across an expert panel regarding the role of existing and novel technologies in osteoarthritis research. To direct future cross-disciplinary research it aimed to identify which could be adopted to subcategorise patients with osteoarthritis (OA). Design: An online questionnaire was formulated based on technologies which might aid OA research and subcategorisation. During a two-day face-to-face meeting concordance of expert opinion was established with surveys (23 questions) before, during and at the end of the meeting (Rounds 1, 2 and 3, respectively). Experts spoke on current evidence for imaging, genomics, epigenomics, proteomics, metabolomics, biomarkers, activity monitoring, clinical engineering and machine learning relating to subcategorisation. For each round of voting, ≥80% votes led to consensus and ≤20% to exclusion of a statement. Results: Panel members were unanimous that a combination of novel technological advances have potential to improve OA diagnostics and treatment through subcategorisation, agreeing in Rounds 1 and 2 that epigenetics, genetics, MRI, proteomics, wet biomarkers and machine learning could aid subcategorisation. Expert presentations changed participants' opinions on the value of metabolomics, activity monitoring and clinical engineering, all reaching consensus in Round 2. X-rays lost consensus between Rounds 1 and 2; clinical X-rays reached consensus in Round 3. Conclusion: Consensus identified that 9 of the 11 technologies should be targeted towards OA subcategorisation to address existing OA research technology and knowledge gaps. These novel, rapidly evolving technologies are recommended as a focus for emergent, cross-disciplinary osteoarthritis research programmes.

Identifying non-specific low back pain clinical subgroups from sitting and standing repositioning posture tasks using a novel Cardiff Dempster-Shafer Theory Classifier.

BACKGROUND: Low back pain (LBP) classification systems are used to deliver targeted treatments matched to an individual profile, however, distinguishing between different subsets of LBP remains a clinical challenge. METHODS: A novel application of the Cardiff Dempster-Shafer Theory Classifier was employed to identify clinical subgroups of LBP on the basis of repositioning accuracy for subjects performing a sitting and standing posture task. 87 LBP subjects, clinically subclassified into flexion (n = 50), passive extension (n = 14), and active extension (n = 23) motor control impairment subgroups and 31 subjects with no LBP were recruited. Thoracic, lumbar and pelvic repositioning errors were quantified. The Classifier then transformed the error variables from each subject into a set of three belief values: (i) consistent with no LBP, (ii) consistent with LBP, (iii) indicating either LBP or no LBP. FINDINGS: In discriminating LBP from no LBP the Classifier accuracy was 96.61%. From no-LBP, subsets of flexion LBP, active extension and passive extension achieved 93.83, 98.15% and 97.62% accuracy, respectively. Classification accuracies of 96.8%, 87.7% and 70.27% were found when discriminating flexion from passive extension, flexion from active extension and active from passive extension subsets, respectively. Sitting lumbar error magnitude best discriminated LBP from no LBP (92.4% accuracy) and the flexion subset from no-LBP (90.1% accuracy). Standing lumbar error best discriminated active and passive extension from no LBP (94.4% and 95.2% accuracy, respectively). INTERPRETATION: Using repositioning accuracy, the Cardiff Dempster-Shafer Theory Classifier distinguishes between subsets of LBP and could assist decision making for targeted exercise in LBP management.

Does Gait Retraining Have the Potential to Reduce Medial Compartmental Loading in Individuals With Knee Osteoarthritis While Not Adversely Affecting the Other Lower Limb Joints? A Systematic Review.

OBJECTIVES: To review the literature regarding gait retraining to reduce knee adduction moments and their effects on hip and ankle biomechanics. DATA SOURCES: Twelve academic databases were searched from inception to January 2019. Key words "walk*" OR "gait," "knee" OR "adduction moment," "osteoarthriti*" OR "arthriti*" OR "osteo arthriti*" OR "OA," and "hip" OR "ankle" were combined with conjunction "and" in all fields. STUDY SELECTION: Abstracts and full-text articles were assessed by 2 individuals against a predefined criterion. DATA SYNTHESIS: Of the 11 studies, sample sizes varied from 8-40 participants. Eight different gait retraining styles were evaluated: hip internal rotation, lateral trunk lean, toe-in, toe-out, increased step width, medial thrust, contralateral pelvic drop, and medial foot weight transfer. Using the Black and Downs tool, the methodological quality of the included studies was fair to moderate ranging between 12 of 25 to 18 of 28. Trunk lean and medial thrust produced the biggest reductions in first peak knee adduction moment. Studies lacked collective sagittal and frontal plane hip and ankle joint biomechanics. Generally, studies had a low sample size of healthy participants with no osteoarthritis and assessed gait retraining during 1 laboratory visit while not documenting the difficulty of the gait retraining style. CONCLUSIONS: Gait retraining techniques may reduce knee joint loading; however, the biomechanical effects to the pelvis, hip, and ankle is unknown, and there is a lack of understanding for the ease of application of the gait retraining styles.

Which osteoarthritic gait features recover following total knee replacement surgery?

BACKGROUND: Gait analysis can be used to measure variations in joint function in patients with knee osteoarthritis (OA), and is useful when observing longitudinal biomechanical changes following Total Knee Replacement (TKR) surgery. The Cardiff Classifier is an objective classification tool applied previously to examine the extent of biomechanical recovery following TKR. In this study, it is further developed to reveal the salient features that contribute to recovery towards healthy function. METHODS: Gait analysis was performed on 30 patients before and after TKR surgery, and 30 healthy controls. Median TKR follow-up time was 13 months. The combined application of principal component analysis (PCA) and the Cardiff Classifier defined 18 biomechanical features that discriminated OA from healthy gait. Statistical analysis tested whether these features were affected by TKR surgery and, if so, whether they recovered to values found for the controls. RESULTS: The Cardiff Classifier successfully discriminated between OA and healthy gait in all 60 cases. Of the 18 discriminatory features, only six (33%) were significantly affected by surgery, including features in all three planes of the ground reaction force (p<0.001), ankle dorsiflexion moment (p<0.001), hip adduction moment (p = 0.003), and transverse hip angle (p = 0.007). All but two (89%) of these features remained significantly different to those of the control group after surgery. CONCLUSIONS: This approach was able to discriminate gait biomechanics associated with knee OA. The ground reaction force provided the strongest discriminatory features. Despite increased gait velocity and improvements in self-reported pain and function, which would normally be clinical indicators of recovery, the majority of features were not affected by TKR surgery. This TKR cohort retained pre-operative gait patterns; reduced sagittal hip and knee moments, decreased knee flexion, increased hip flexion, and reduced hip adduction. The changes that were associated with surgery were predominantly found at the ankle and hip, rather than at the knee.

Comparison of gait, functional activities, and patient-reported outcome measures in patients with knee osteoarthritis and healthy adults using 3D motion analysis and activity monitoring: an exploratory case-control analysis.

OBJECTIVE: To examine functional performance differences using kinematic and kinetic analysis between participants with and without knee osteoarthritis (OA) to determine which outcomes best characterize persons with and without knee OA. METHODS: Participants with unilateral moderate knee OA (Kellgren-Lawrence grades 2 or 3) and controls without knee pain were matched for age, gender, and body mass index. Primary outcomes included temporal parameters, joint rotations and moments, and ground reaction forces assessed via 3D motion capture during walking and ascending/descending stairs. Secondary outcomes included timed functional activities (sit to stand; tying shoelaces), 48 hrs lower limb activity monitoring, and patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, European Quality of Life-5 Dimensions). RESULTS: Eight matched pairs were analyzed. Compared with controls, OA participants exhibited significant reductions in peak frontal hip and sagittal knee moments, and decreased peak anterior ground reaction force with the affected limb while walking. Ascending stairs, OA participants had slower speed, fewer strides per minute, longer cycle and stance times, and increased trunk range of motion (ROM) in assessments of both limbs; longer swing time and reduced ankle ROM in the affected limb; and increased knee frontal ROM in the unaffected limb. Descending stairs, OA participants had fewer strides per minute and decreased trunk transverse ROM in assessments of both limbs; increased knee frontal ROM in the affected limb; and longer strides, shorter stance and cycle times, increased trunk sagittal and decreased knee transverse ROMs in the unaffected limbs vs controls. Compared with controls, OA participants had slower walking cadence (120-130 vs 100-110 steps/min, respectively), took significantly longer on timed functional measures, and had significantly worse scores in patient-reported outcomes. CONCLUSION: Several objectives and patient-reported measures examined in this study could potentially be considered as outcomes in pharmacologic or physical therapy OA trials.

Notch3 activation modulates cell growth behaviour and cross-talk to Wnt/TCF signalling pathway.

Notch3 is one of the four Notch receptors identified in mammal and expressed mainly in the arterial smooth muscle cells of human adult. Signalling via Notch3 is thought to be important in maintaining the phenotypic stability of the cells, but the nature of the signalling and its regulation to other signalling pathways are largely unknown. To understand further of the cellular function of Notch3 signalling, we generated cell lines stably expressing a constitutively active form of human Notch3 comprising of its soluble intracellular domain (N3IC). The N3IC expressing cells showed accelerated proliferation, decreased migration, increased cell surface N-cadherin, and growth in a colonised fashion that was reversible by N-cadherin blockade. N3IC expressing cells were also protected significantly against staurosporine-induced apoptosis and exhibited lower caspase 3/7 activity, accompanied by up-regulation of pAKT compared to control cells. We also found a complex cross-talk between Notch3 signalling and the Wnt pathway. N3IC stimulated Wnt-independent T-cell factor (TCF, the target transcription factor in the Wnt pathway) activation which was associated with increased Tyr-142 phosphorylation of beta-catenin. In contrast N3IC suppressed TCF activation in response to LiCl, which mimics the Wnt-dependent TCF activation mechanism. We conclude that Notch3 promotes cell growth and survival by activating PI3-kinase/AKT pathway; N-cadherin participates in the change of cell growth caused by Notch3 activation; and Notch3 signalling has dual-effects on the Wnt/TCF pathway suggesting a buffering role that Notch3 signalling may play in balancing these two important signalling pathways in regulating cell function.

Reduction, classification and ranking of motion analysis data: an application to osteoarthritic and normal knee function data.

There are certain major obstacles to using motion analysis as an aid to clinical decision making. These include: the difficulty in comprehending large amounts of both corroborating and conflicting information; the subjectivity of data interpretation; the need for visualization; and the quantitative comparison of temporal waveform data. This paper seeks to overcome these obstacles by applying a hybrid approach to the analysis of motion analysis data using principal component analysis (PCA), the Dempster-Shafer (DS) theory of evidence and simplex plots. Specifically, the approach is used to characterise the differences between osteoarthritic (OA) and normal (NL) knee function data and to produce a hierarchy of those variables that are most discriminatory in the classification process. Comparisons of the results obtained with the hybrid approach are made with results from artificial neural network analyses.