LONGITUDINAL ADAPTATIONS IN MUSCLE STRENGTH, FUNCTIONAL PERFORMANCE, GAIT BIOMECHANICS, AND PATIENT-REPORTED FUNCTION AFTER UNILATERAL TOTAL KNEE ARTHROPLASTY

Objective: The aims of this research were to identify gaps in the literature related to impairments after total knee arthroplasty (TKA) (Aim 1) and define recovery between 3 and 6 months after TKA across four domains: 1) hip and knee muscle performance, 2) functional performance, 3) patient-reported function, and 4) biomechanics of walking and stair descent (Aim 2). Additionally, this project sought to explore the relationships between each domain (Aim 3) and establish predictive models to allow clinicians to use clinical measures to predict future gait biomechanics in patients after TKA (Aim 4). Ultimately, the results of this research would quantify post-rehabilitative recovery after TKA and identify potential targets for objective criteria needed for discharge from outpatient rehabilitation. Participants: Thirty-nine individuals completed the study protocol, 21 in the TKA group (7 male, 14 female, height: 1.68 ± 0.08 m, mass: 90.95 ± 21.04 kg, BMI: 32.27 ± 7.4 kg/m2, Age: 60.6 ± 8.1 years) and 18 matched control subjects (7 male, 11 female, height: 1.69 ± 0.10 m, mass: 83.69 ± 20.2 kg, BMI: 29.2 ± 5.5 kg/m2, Age: 61.2 ± 8.8 years). Methods: For Aim 1, a systematic review of the literature related to the four previously stated domains was conducted. In Aims 2-4, a longitudinal design with 3 and 6 months post-surgery assessment time points was used for the TKA group. At both assessment time points, participants underwent maximal voluntary isometric strength testing of bilateral hip abduction, hip external rotation, and knee extension to determine peak strength and rate of torque development (RTD). Participants also performed the five-time sit-to-stand test (FTSTS) and underwent three-dimensional motion analysis while walking at a self-selected speed and during a stair descent task. Patient-reported function was measured using the Knee Injury & Osteoarthritis Outcome Score (KOOS). The control subjects completed the same testing procedures at a single time point. Main Outcome Measures: Outcomes were assessed across four domains. The first domain included peak isometric muscle strength and RTD of hip abduction, hip external rotation, and knee extension. The second and third domains represented functional performance as assessed by the FTSTS and patient-reported function as measured by the KOOS, respectively. The final domain included hip and knee joint kinematics and kinetics during walking and stair descent as measured using three-dimensional motion analysis and inverse dynamics. Statistical Analysis: Aim 1: no formal statistics were utilized in the systematic review. Aim 2 utilized paired sample t-tests for between-limb (operative vs non-operative) and within-limb (3 months vs 6 months post-surgery) comparisons across all four domains. Additionally, independent two-sample t-tests were used to compare the operative and non-operative limbs of the TKA group to the matched control group. In Aim 3, Pearson product-moment correlations were performed to assess the relationships between muscle performance, FTSTS performance, and KOOS scores in the TKA group at 1) 3 months post-surgery, 2) 6 months post-surgery, and 3) between the improvements in these outcomes from 3 to 6 months post-surgery. Lastly, Aim 4 utilized Pearson product-moment correlations and stepwise multiple linear regressions to develop a predictive model using clinical measures assessed at 3 months post-operatively to predict knee flexion excursion during walking at 6 months post-surgery. Results: Aim 1: Improvements in KOOS scores, deficits in peak quadriceps strength, and altered knee joint biomechanics during walking are present during the first 6 months following TKA. Limited evidence exists regarding hip muscle strength deficits, FTSTS performance, and stair descent biomechanics after TKA. Aim 2: Quadriceps and hip external rotation peak strength and RTD, FTSTS performance, gait and stair descent biomechanics, and KOOS scores all demonstrated significant, but modest, improvement between 3 and 6 months post-surgery. However, persistent deficits in quadriceps and hip external rotation peak strength and RTD, FTSTS, movement biomechanics, and KOOS scores compared to control subjects indicate incomplete recovery after TKA both immediately after rehabilitation and following the early post-rehabilitative period. Aim 3: Peak hip muscle strength and FTSTS performance are significantly correlated with KOOS Pain, activities of daily living, and Sport subscales at 3 months post-surgery. Fewer relationships were observed at 6 months post-surgery and between improvements from 3 to 6 months. Aim 4: Quadriceps RTD, hip external rotation RTD, and FTSTS performance were predictive of knee flexion excursion during walking, with quadriceps RTD the strongest of the three predictors. Faster quadriceps RTD, slower hip external rotation RTD, and faster FTSTS performance are predicted to lead to greater knee flexion excursion. Conclusions: Modest improvement in muscle strength and RTD, FTSTS performance, patient-reported function, and biomechanics occur during the post-rehabilitative period after TKA, but all domains remain impaired compared to matched control subjects. Furthermore, muscle strength and RTD and FTSTS performance contribute to greater patient-perceived function and future knee flexion excursion during walking. In order to improve outcomes across domains after TKA, emphasizing improvement in muscle strength, RTD, and FTSTS ability during the first 3 months after surgery is critical as persistent deficits do not resolve by 6 months post-surgery. Lastly, maximizing quadriceps RTD by 3 months post-surgery is likely to lead to improved walking biomechanics at 6 months post-surgery

Modifications in Early Rehabilitation Protocol after Rotator Cuff Repair : EMG Studies

La déchirure de la coiffe des rotateurs est une des causes les plus fréquentes de douleur et de dysfonctionnement de l'épaule. La réparation chirurgicale est couramment réalisée chez les patients symptomatiques et de nombreux efforts ont été faits pour améliorer les techniques chirurgicales. Cependant, le taux de re-déchirure est encore élevé ce qui affecte les stratégies de réhabilitation post-opératoire. Les recommandations post-chirurgicales doivent trouver un équilibre optimal entre le repos total afin de protéger le tendon réparé et les activités préconisées afin de restaurer l'amplitude articulaire et la force musculaire. Après une réparation de la coiffe, l'épaule est le plus souvent immobilisée grâce à une écharpe ou une orthèse. Cependant, cette immobilisation limite aussi la mobilité du coude et du poignet. Cette période qui peut durer de 4 à 6 semaines où seuls des mouvements passifs peuvent être réalisés. Ensuite, les patients sont incités à réaliser les exercices actifs assistés et des exercices actifs dans toute la mobilité articulaire pour récupérer respectivement l’amplitude complète de mouvement actif et se préparer aux exercices de résistance réalisés dans la phase suivante de la réadaptation. L’analyse électromyographique des muscles de l'épaule a fourni des évidences scientifiques pour la recommandation de beaucoup d'exercices de réadaptation au cours de cette période. Les activités sollicitant les muscles de la coiffe des rotateurs à moins de 20% de leur activation maximale volontaire sont considérés sécuritaires pour les premières phases de la réhabilitation. À partir de ce concept, l'objectif de cette thèse a été d'évaluer des activités musculaires de l'épaule pendant des mouvements et exercices qui peuvent théoriquement être effectués au cours des premières phases de la réhabilitation. Les trois questions principales de cette thèse sont : 1) Est-ce que la mobilisation du coude et du poignet produisent une grande activité des muscles de la coiffe? 2) Est-ce que les exercices de renforcement musculaire du bras, de l’avant-bras et du torse produisent une grande activité dans les muscles de la coiffe? 3) Au cours d'élévations actives du bras, est-ce que le plan d'élévation affecte l'activité de la coiffe des rotateurs? Dans notre première étude, nous avons évalué 15 muscles de l'épaule chez 14 sujets sains par électromyographie de surface et intramusculaire. Nos résultats ont montré qu’avec une orthèse d’épaule, les mouvements du coude et du poignet et même quelques exercices de renforcement impliquant ces deux articulations, activent de manière sécuritaire les muscles de ii la coiffe. Nous avons également introduit des tâches de la vie quotidienne qui peuvent être effectuées en toute sécurité pendant la période d'immobilisation. Ces résultats peuvent aider à modifier la conception d'orthèses de l’épaule. Dans notre deuxième étude, nous avons montré que l'adduction du bras réalisée contre une mousse à faible densité, positionnée pour remplacer le triangle d’une orthèse, produit des activations des muscles de la coiffe sécuritaires. Dans notre troisième étude, nous avons évalué l'électromyographie des muscles de l’épaule pendant les tâches d'élévation du bras chez 8 patients symptomatiques avec la déchirure de coiffe des rotateurs. Nous avons constaté que l'activité du supra-épineux était significativement plus élevée pendant l’abduction que pendant la scaption et la flexion. Ce résultat suggère une séquence de plan d’élévation active pendant la rééducation. Les résultats présentés dans cette thèse, suggèrent quelques modifications dans les protocoles de réadaptation de l’épaule pendant les 12 premières semaines après la réparation de la coiffe. Ces suggestions fournissent également des évidences scientifiques pour la production d'orthèses plus dynamiques et fonctionnelles à l’articulation de l’épaule.Rotator cuff tear is one of the most common causes of shoulder pain and dysfunction. The operative repair has been widely performed for symptomatic patients and many efforts have been done to improve the surgical techniques. However, the re-tear rate is still high and this affects post-repair rehabilitation strategies. Post-surgical care should balance between the restriction imposed to protect the repaired tendon and the activities prescribed to restore range of motion and muscle strength. Frequently, early after rotator cuff repair, shoulder is immobilized in a sling or abduction orthosis, but this immobilization includes elbow and wrist joints as well. In this period that may last 4-6 weeks, only passive range of motion exercises are performed. After removing the immobilizer, patients are encouraged to do active assisted and active range of motion exercises respectively to regain the full active range of motion and be prepared for the resistance exercises in the following phase of rehabilitation. Electromyography of shoulder muscles has provided scientific basis for many of rehabilitation exercises during this period. Anecdotally, the activities of less than 20% of the maximal voluntary contraction of rotator cuff muscles are considered safe for the first phases of rehabilitation after rotator cuff repair. Using this concept, the aim of this dissertation is to evaluate the activity of shoulder musculature during some movements and exercises that can theoretically be performed during the early phases of rehabilitation. Three main questions of this thesis are: 1) Do elbow and wrist mobilizations highly activate rotator cuff muscles? 2) Do some resistance exercises of arm, forearm and chest muscles produce high activity in rotator cuff muscles? 3) During active arm elevation, does the plane of elevation affect rotator cuff activity? In our first study, we evaluated 15 shoulder muscles in 14 healthy subjects with both surface and indwelling EMG. Our results showed that while wearing a shoulder orthosis, elbow and wrist movements and even some resistance training involving these two joints, would minimally activate the rotator cuff muscles and can be considered safe. We also introduced some daily living tasks that can be performed safely during immobilization period. These findings may help to modify the design of current shoulder orthoses. In the second study, we also showed that resisted arm adduction against a low-density foam that replaced the hard wedge of orthosis would not highly activate the cuff muscles. In our final study, we evaluated the EMG of shoulder musculature during arm elevation tasks in 8 symptomatic patients with rotator cuff tears. We found that supraspinatus activity during arm elevation is significantly higher in abduction plane than in scaption and flexion planes in patients with rotator cuff tears. This suggested a plane sequences for active range of motion exercises during rehabilitation. The findings that are presented in this dissertation, suggest some modifications in the rehabilitation protocols during the first 12 weeks after rotator cuff repair. These suggestions also provide a scientific basis for producing more dynamic and functional shoulder orthoses

The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury

Spinal cord injury (SCI) triggers neuroinflammation, and subsequently secondary degeneration and oligodendrocyte (OL) death. We report that the alarmin interleukin (IL)−1α is produced by damaged microglia after SCI. Intra-cisterna magna injection of IL-1α in mice rapidly induces neutrophil infiltration and OL death throughout the spinal cord, mimicking the injury cascade seen in SCI sites. These effects are abolished through co-treatment with the IL-1R1 antagonist anakinra, as well as in IL-1R1-knockout mice which demonstrate enhanced locomotor recovery after SCI. Conditional restoration of IL-1R1 expression in astrocytes or endothelial cells (ECs), but not in OLs or microglia, restores IL-1α-induced effects, while astrocyte- or EC-specific Il1r1 deletion reduces OL loss. Conditioned medium derived from IL-1α-stimulated astrocytes results in toxicity for OLs; further, IL-1α-stimulated astrocytes generate reactive oxygen species (ROS), and blocking ROS production in IL-1α-treated or SCI mice prevented OL loss. Thus, after SCI, microglia release IL-1α, inducing astrocyte- and EC-mediated OL degeneration

Complex and Adaptive Dynamical Systems: A Primer

An thorough introduction is given at an introductory level to the field of quantitative complex system science, with special emphasis on emergence in dynamical systems based on network topologies. Subjects treated include graph theory and small-world networks, a generic introduction to the concepts of dynamical system theory, random Boolean networks, cellular automata and self-organized criticality, the statistical modeling of Darwinian evolution, synchronization phenomena and an introduction to the theory of cognitive systems. It inludes chapter on Graph Theory and Small-World Networks, Chaos, Bifurcations and Diffusion, Complexity and Information Theory, Random Boolean Networks, Cellular Automata and Self-Organized Criticality, Darwinian evolution, Hypercycles and Game Theory, Synchronization Phenomena and Elements of Cognitive System Theory.Comment: unformatted version of the textbook; published in Springer, Complexity Series (2008, second edition 2010

Critical phenomena in complex networks

The combination of the compactness of networks, featuring small diameters, and their complex architectures results in a variety of critical effects dramatically different from those in cooperative systems on lattices. In the last few years, researchers have made important steps toward understanding the qualitatively new critical phenomena in complex networks. We review the results, concepts, and methods of this rapidly developing field. Here we mostly consider two closely related classes of these critical phenomena, namely structural phase transitions in the network architectures and transitions in cooperative models on networks as substrates. We also discuss systems where a network and interacting agents on it influence each other. We overview a wide range of critical phenomena in equilibrium and growing networks including the birth of the giant connected component, percolation, k-core percolation, phenomena near epidemic thresholds, condensation transitions, critical phenomena in spin models placed on networks, synchronization, and self-organized criticality effects in interacting systems on networks. We also discuss strong finite size effects in these systems and highlight open problems and perspectives.Comment: Review article, 79 pages, 43 figures, 1 table, 508 references, extende

Detection of QTL affecting flesh quality traits (body lipid percentage and flesh colour) using molecular markers (microsatellites and AFLP markers) in Atlantic salmon (Salmo salar L.)

Flesh colour and fillet fat percentage are the two most important attributes to salmon fillet quality. A medium genetic component to body lipid percentage within commercial lines has previously been shown (h2 = 0.17-0.24). A low level of heritability (h2 = 0.16) has also been reported for flesh colour in Atlantic salmon. To investigate whether this genetic component includes loci of major effect, a genome-wide QTL scan was performed with commercially bred Atlantic salmon (Landcatch Natural Selection). Five large full-sib families (10 parents with 153 offspring) were genotyped using microsatellite markers. To utilize the large difference between sire and dam recombination rate, a two-stage genotyping was employed. Initially, the parents and offspring were genotyped for two microsatellite markers per linkage group, and sire based QTL analysis was used to detect linkage groups with significant effects on those flesh quality traits. A linear-regression based interval as analytical method was applied for QTL detection. The results revealed evidence of QTLs affecting percentage fat percentage and flesh colour on linkage groups LNS16 and LNS1 respectively. To confirm the QTL and to provide an improved estimate of position, a dam-based analysis was then employed. One major QTL was located on the genome-wide significance level for percentage fat percentage. Microsatellite marker Ssa0016NVH (at position of 1.3 cM) was found to be tightly linked to QTL affecting percentage fat percentage. In addition, a QTL affecting flesh colour was found to be flanked by microsatellite markers Ssa9.44NUIG at position of 68.7 cM and Ssa0021NVH at position of 50.6 on linkage group LNS16. The evidence for suggestive QTL affecting flesh colour on linkage group LNS1 was also revealed. In order to increase marker density within these and other linkage groups, AFLP markers were employed, 24 primer combinations resulted in a total of 489 polymorphic fragments. Among 11 fragments that were found to be linked to the microsatellite markers on linkage group LNS16, four fragments (AAG-CAC328, AGG-CAG447, AGG-CTA237 and AGG-CTC237) were tightly linked to microsatellite marker Ssa9.44NUIG, but none were found to be linked to microsatellite Ssa0021NVH. Moreover, none of the AFLP markers were found to be linked to microsatellites residing on linkage group LNS1. Using a constructed map of microsatellite and AFLP markers for linkage group LNS16, the dam based analysis revealed a significant QTL for flesh colour at the location of 189 cM, while the sire based analysis detected a significant QTL for fat percentage at the location of 80 cM. Considering the dominant nature and clustering character of AFLP markers, it was concluded that a certain primer combination in AFLP markers could be of limited use for fine mapping and QTL detection in Atlantic salmon