Extracellular matrix compression temporally regulates microvascular angiogenesis.

Mechanical cues influence tissue regeneration, and although vasculature is known to be mechanically sensitive, little is known about the effects of bulk extracellular matrix deformation on the nascent vessel networks found in healing tissues. Previously, we found that dynamic matrix compression in vivo potently regulated revascularization during bone tissue regeneration; however, whether matrix deformations directly regulate angiogenesis remained unknown. Here, we demonstrated that load initiation time, magnitude, and mode all regulate microvascular growth, as well as upstream angiogenic and mechanotransduction signaling pathways. Immediate load initiation inhibited angiogenesis and expression of early sprout tip cell selection genes, while delayed loading enhanced microvascular network formation and upstream signaling pathways. This research provides foundational understanding of how extracellular matrix mechanics regulate angiogenesis and has critical implications for clinical translation of new regenerative medicine therapies and physical rehabilitation strategies designed to enhance revascularization during tissue regeneration.

Individual and contextual predictors of retention in Special Olympics for youth with intellectual disability: who stays involved?

BACKGROUND: Despite the recognised benefits of sport, participation is often reported to be low for youth with intellectual disability (ID). The current study was the first to longitudinally examine sport retention in this population, a critical aspect of ensuring participation. METHODS: Study participants were parents/caregivers of athletes with ID involved in community Special Olympics (SO), 11-22 years of age (N = 345). Participants completed an online survey in 2012 that included caregiver demographic and athlete intrapersonal, interpersonal and broader contextual variables. Retention rates for 2019 were determined using the SO provincial registration lists. RESULTS: Of the 345 survey participants, 81.7% remained active athletes in 2019. Caregiver demographic and athlete intrapersonal factors were largely unrelated to retention. In contrast, retention was associated with the frequency and number of sports athletes participated in, the perceived psychosocial gains of SO involvement and the environmental supports that were available to facilitate participation; frequency of sport participation was the strongest predictor of remaining a registered athlete. CONCLUSIONS: This study has implications for future initiatives aimed at increasing sport retention in a population that struggles to be engaged in sport. Efforts should focus on the athlete experience and sport-specific factors. Coaches and caregivers can foster positive experiences and play an important role in continued sport participation.

The quality of life of children with severe developmental disabilities.

BACKGROUND: Research examining the quality of life (QoL) of children with severe developmental disabilities (SDD) is limited. The present study examines parent perceptions of child QoL in children with SDD compared with typically developing (TD) children and then examines predictors of QoL for the SDD group. METHOD: Parents of 246 children with SDD (aged 4 to 19 years) and 210 TD children (aged 4 to 18 years) responded to an online survey. QoL was measured using a composite variable composed of the child's happiness, achievement of potential and friendship quality. RESULTS: Children with DD had lower QoL ratings than TD children. In children with DD, higher QoL was related to younger age, higher adaptive skills, lower maladaptive behaviour, lower parent psychological distress and higher satisfaction with the child's education. CONCLUSIONS: Interventions to promote positive outcomes for children with SDD should target both characteristics of the individual and the environment.

A systematic literature review of the physical and psychosocial correlates of Special Olympics participation among individuals with intellectual disability.

BACKGROUND: Special Olympics (SO) is commonly cited to play an important role in the lives of individuals with intellectual disabilities (ID). The purpose of the current review was to (a) synthesise key findings regarding the physical, psychological/emotional, social and/or intellectual/cognitive correlates of SO participation for individuals with ID and (b) highlight limitations in the extant research as well as directions for future research. METHOD: A systematic review of electronic databases was undertaken. A total of 46 articles were confirmed to meet study criteria. Quality assessments of included studies were conducted using checklists from the Scottish Intercollegiate Guidelines Network methodology checklists (SIGN 50; SIGN 2008). RESULTS: There was a larger amount of support for physical, psychological/emotional and social outcomes as compared with cognitive/intellectual outcomes; however, many studies were confounded by measurement difficulties, sampling procedures and a lack of replicable methods, which hinder generalisation of results. CONCLUSIONS: This review highlights the need for a continued critical focus on SO programme evaluation research with more rigorous and replicable methods.

Community participation of youth with intellectual disability and autism spectrum disorder.

BACKGROUND: Community participation is associated with a range of positive developmental outcomes; however, the frequency, depth and resources associated with participation for youth with intellectual disability (ID) and autism spectrum disorder (ASD) are not well understood. METHOD: Caregivers of 212 youth with ASD and ID and only ID, aged 11-22 years, completed an online survey. Comparisons were made of caregiver reports of diversity and frequency of participation, levels of participation involvement and related environmental barriers and supports. RESULTS: The diversity and frequency of community participation of youth with ASD and ID approximated that of youth with ID only. Youth with ASD and ID were reported to be significantly less involved in the community activities in which they participated. Environmental features, and in particular, the social demands of community-based activities, were significant barriers to youths' participation. CONCLUSIONS: The current study highlights individual and environmental factors amenable to intervention that may foster successful community participation among youth with ASD and ID.

Patient-specific chondrolabral contact mechanics in patients with acetabular dysplasia following treatment with peri-acetabular osteotomy.

OBJECTIVE: Using a validated, patient-specific finite element (FE) modeling protocol, we evaluated cartilage and labrum (i.e., chondrolabral) mechanics before and after peri-acetabular osteotomy (PAO) to provide insight into the ability of this procedure to improve mechanics in dysplastic hips. DESIGN: Five patients with acetabular dysplasia were recruited in this case-controlled, prospective study. Models, which included anatomy for bone, cartilage, and labrum, were generated from computed tomography (CT) arthrography scans acquired before and after PAO. Cartilage and labrum contact stress and contact area were quantified overall and regionally. Load supported by the labrum, expressed as a percentage of the total hip force, was analyzed. RESULTS: Percent cartilage contact area increased post-operatively overall, medially, and superiorly. Peak acetabular contact stress decreased overall, laterally, anteriorly, and superiorly. Average contact stress decreased overall, laterally, anteriorly, and posteriorly. Only average contact stress on the superior labrum and peak labrum stress overall decreased. Load supported by the labrum did not change significantly. CONCLUSIONS: PAO was efficacious at medializing cartilage contact and reducing cartilage contact stresses, and therefore may minimize deleterious loading to focal cartilage lesions, subchondral cysts, and cartilage delaminations often observed in the lateral acetabulum of dysplastic hips. However, the excessively prominent, hypertrophied labrum of dysplastic hips remains in contact with the femoral head, which continues to load the labrum following PAO. The clinical ramifications of continued labral loading following PAO are not known. However, it is plausible that failure to reduce the load experienced by the labrum could result in end-stage hip OA following PAO.

Psychosocial correlates of psychiatric diagnoses and maladaptive behaviour in youth with severe developmental disability.

BACKGROUND: We know little about the correlates of mental health problems in youth with severe and profound intellectual disability (ID), as most research includes these youth within larger samples that include greater proportions of mild and moderate disability. The purpose of the current study was to identify the child, family and psychosocial characteristics that were associated with the presence of psychiatric diagnoses and maladaptive behaviour in youth with severe ID. METHODS: Participants were 141 parents of youth with severe or profound levels of ID, 4 to 18 years of age. The mean age of children was 11.04 years (SD = 3.38), with 68% male and 39% with autism spectrum disorder (ASD). Parents completed a primarily online survey of child and family characteristics, negative life events, family quality of life and their own mental health. RESULTS: Logistic regression analyses revealed that youth with a psychiatric diagnosis had higher levels of adaptive behaviour and experienced more negative life events than youth without psychiatric diagnosis, while the presence of clinically significant maladaptive behaviour was related to higher levels of adaptive behaviour, parents' mental health problems and lower family quality of life. Child age, gender, ASD status and financial hardship were not related to either outcome variable. CONCLUSIONS: Youth with severe and profound ID who experience psychosocial stressors are more likely reported to have mental health problems than youth without such stressors. It is likely that a combination of child and family based interventions, along with with policies that address larger systemic issues of social adversity, are needed to promote mental health and treat psychopathology when it arises.

Predictors of distress and well-being in parents of young children with developmental delays and disabilities: the importance of parent perceptions.

BACKGROUND: Moving from family-centred to child-centred models of service delivery can be stressful for parents as their young children with developmental delays and disabilities transition into school. The purpose of this paper was to explore and compare predictors of both distress and well-being in parents during this transition period. METHODS: A sample of 155 mothers of 113 boys and 42 girls participated in the study. The mean age of the children was 4.9 years and their diagnoses included autism spectrum disorder (52%); unspecified intellectual disability/developmental delay (26%); Down syndrome (12%); other genetic conditions (4%) and other diagnoses (6%). Participants completed surveys primarily online focusing on child characteristics, family resources, parent coping strategies, parental distress and positive gain. RESULTS: Multiple regression analyses were conducted to determine predictors of parent reported distress and positive gain. Parent coping variables were the strongest predictors of both positive gain and parental distress, with reframing emerging as a predictor of positive gain and parent empowerment emerging as a predictor of both greater positive gain and lower parental distress. CONCLUSIONS: The results of this study highlight not only the importance of including positive as well as negative outcomes in research with parents but also the importance of including parent characteristics such as coping strategies (e.g. reframing and empowerment/self-efficacy) as potential predictors of outcome in such studies.

Computed tomography arthrography with traction in the human hip for three-dimensional reconstruction of cartilage and the acetabular labrum.

AIM: To develop and demonstrate the efficacy of a computed tomography arthrography (CTA) protocol for the hip that enables accurate three-dimensional reconstructions of cartilage and excellent visualization of the acetabular labrum. MATERIALS AND METHODS: Ninety-three subjects were imaged (104 scans); 68 subjects with abnormal anatomy, 11 patients after periacetabular osteotomy surgery, and 25 subjects with normal anatomy. Fifteen to 25 ml of contrast agent diluted with lidocaine was injected using a lateral oblique approach. A Hare traction splint applied traction during CT. The association between traction force and intra-articular joint space was assessed qualitatively under fluoroscopy. Cartilage geometry was reconstructed from the CTA images for 30 subjects; the maximum joint space under traction was measured. RESULTS: Using the Hare traction splint, the intra-articular space and boundaries of cartilage could be clearly delineated throughout the joint; the acetabular labrum was also visible. Dysplastic hips required less traction (∼5 kg) than normal and retroverted hips required (>10 kg) to separate the cartilage. An increase in traction force produced a corresponding widening of the intra-articular joint space. Under traction, the maximum width of the intra-articular joint space during CT ranged from 0.98-6.7 mm (2.46 ± 1.16 mm). CONCLUSIONS: When applied to subjects with normal and abnormal hip anatomy, the CTA protocol presented yields clear delineation of the cartilage and the acetabular labrum. Use of a Hare traction splint provides a simple, cost-effective method to widen the intra-articular joint space during CT, and provides flexibility to vary the traction as required.

A new sensor for measurement of dynamic contact stress in the hip.

Various techniques exist for quantifying articular contact stress distributions, an important class of measurements in the field of orthopaedic biomechanics. In situations where the need for dynamic recording has been paramount, the approach of preference has involved thin-sheet multiplexed grid-array transducers. To date, these sensors have been used to study contact stresses in the knee, shoulder, ankle, wrist, and spinal facet joints. Until now, however, no such sensor had been available for the human hip joint due to difficulties posed by the deep, bi-curvilinear geometry of the acetabulum. We report here the design and development of a novel sensor capable of measuring dynamic contact stress in human cadaveric hip joints (maximum contact stress of 20 MPa and maximum sampling rate 100 readings/s). Particular emphasis is placed on issues concerning calibration, and on the effect of joint curvature on the sensor's performance. The active pressure-sensing regions of the sensors have the shape of a segment of an annulus with a 150-deg circumferential span, and employ a polar/circumferential "ring-and-spoke" sensel grid layout. There are two sensor sizes, having outside radii of 44 and 48 mm, respectively. The new design was evaluated in human cadaver hip joints using two methods. The stress magnitudes and spatial distribution measured by the sensor were compared to contact stresses measured by pressure sensitive film during static loading conditions that simulated heel strike during walking and stair climbing. Additionally, the forces obtained by spatial integration of the sensor contact stresses were compared to the forces measured by load cells during the static simulations and for loading applied by a dynamic hip simulator. Stress magnitudes and spatial distribution patterns obtained from the sensor versus from pressure sensitive film exhibited good agreement. The joint forces obtained during both static and dynamic loading were within ±10% and ±26%, respectively, of the forces measured by the load cells. These results provide confidence in the measurements obtained by the sensor. The new sensor's real-time output and dynamic measurement capabilities hold significant advantages over static measurements from pressure sensitive film.

Sexual knowledge and victimization in adults with autism spectrum disorders.

There is a significant gap in understanding the risk of sexual victimization in individuals with autism spectrum disorders (ASD) and the variables that contribute to risk. Age appropriate sexual interest, limited sexual knowledge and experiences, and social deficits, may place adults with ASD at increased risk. Ninety-five adults with ASD and 117 adults without ASD completed questionnaires regarding sexual knowledge sources, actual knowledge, perceived knowledge, and sexual victimization. Individuals with ASD obtained less of their sexual knowledge from social sources, more sexual knowledge from non-social sources, had less perceived and actual knowledge, and experienced more sexual victimization than controls. The increased risk of victimization by individuals with ASD was partially mediated by their actual knowledge. The link between knowledge and victimization has important clinical implications for interventions.

Patient-specific analysis of cartilage and labrum mechanics in human hips with acetabular dysplasia.

BACKGROUND: Acetabular dysplasia is a major predisposing factor for development of hip osteoarthritis (OA), and may result from alterations to chondrolabral loading. Subject-specific finite element (FE) modeling can be used to evaluate chondrolabral mechanics in the dysplastic hip, thereby providing insight into mechanics that precede OA. OBJECTIVE: To evaluate chondrolabral contact mechanics and congruency in dysplastic hips and normal hips using a validated approach to subject-specific FE modeling. METHODS: FE models of ten subjects with normal acetabula and ten subjects with dysplasia were constructed using a previously validated protocol. Labrum load support, and labrum and acetabular cartilage contact stress and contact area were compared between groups. Local congruency was determined at the articular surface for two simulated activities. RESULTS: The labrum in dysplastic hips supported 2.8-4.0 times more of the load transferred across the joint than in normal hips. Dysplastic hips did not have significantly different congruency in the primary load-bearing regions than normal hips, but were less congruent in some unloaded regions. Normal hips had larger cartilage contact stress than dysplastic hips in the few regions that had significant differences. CONCLUSIONS: The labrum in dysplastic hips has a far more significant role in hip mechanics than it does in normal hips. The dysplastic hip is neither less congruent than the normal hip, nor subjected to elevated cartilage contact stresses. This study supports the concept of an outside-in pathogenesis of OA in dysplastic hips and that the labrum in dysplastic hips should be preserved during surgery.

Finite element predictions of cartilage contact mechanics in hips with retroverted acetabula.

BACKGROUND: A contributory factor to hip osteoarthritis (OA) is abnormal cartilage mechanics. Acetabular retroversion, a version deformity of the acetabulum, has been postulated to cause OA via decreased posterior contact area and increased posterior contact stress. Although cartilage mechanics cannot be measured directly in vivo to evaluate the causes of OA, they can be predicted using finite element (FE) modeling. OBJECTIVE: The objective of this study was to compare cartilage contact mechanics between hips with normal and retroverted acetabula using subject-specific FE modeling. METHODS: Twenty subjects were recruited and imaged: 10 with normal acetabula and 10 with retroverted acetabula. FE models were constructed using a validated protocol. Walking, stair ascent, stair descent and rising from a chair were simulated. Acetabular cartilage contact stress and contact area were compared between groups. RESULTS: Retroverted acetabula had superomedial cartilage contact patterns, while normal acetabula had widely distributed cartilage contact patterns. In the posterolateral acetabulum, average contact stress and contact area during walking and stair descent were 2.6-7.6 times larger in normal than retroverted acetabula (P ≤ 0.017). Conversely, in the superomedial acetabulum, peak contact stress during walking was 1.2-1.6 times larger in retroverted than normal acetabula (P ≤ 0.044). Further differences varied by region and activity. CONCLUSIONS: This study demonstrated superomedial contact patterns in retroverted acetabula vs widely distributed contact patterns in normal acetabula. Smaller posterolateral contact stress in retroverted acetabula than in normal acetabula suggests that increased posterior contact stress alone may not be the link between retroversion and OA.

Multiscale mechanics of articular cartilage: potentials and challenges of coupling musculoskeletal, joint, and microscale computational models.

Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes.

Validation of computational models in biomechanics.

The topics of verification and validation have increasingly been discussed in the field of computational biomechanics, and many recent articles have applied these concepts in an attempt to build credibility for models of complex biological systems. Verification and validation are evolving techniques that, if used improperly, can lead to false conclusions about a system under study. In basic science, these erroneous conclusions may lead to failure of a subsequent hypothesis, but they can have more profound effects if the model is designed to predict patient outcomes. While several authors have reviewed verification and validation as they pertain to traditional solid and fluid mechanics, it is the intent of this paper to present them in the context of computational biomechanics. Specifically, the task of model validation will be discussed, with a focus on current techniques. It is hoped that this review will encourage investigators to engage and adopt the verification and validation process in an effort to increase peer acceptance of computational biomechanics models.

Computational modeling of ligament mechanics.

This article provides a critical review of past and current techniques for the computational modeling of ligaments and tendons. A brief overview of relevant concepts from the fields of continuum mechanics and finite element analysis is provided. The structure and function of ligaments and tendons are reviewed in detail, with emphasis on the relationship of microstructural tissue features to the continuum mechanical hehavior. Experimental techniques for the material characterization of biological soft tissues are discussed. Past and current efforts related to the constitutive modeling of ligaments and tendons are classified by the particular technique and dimensionality. Applications of one-dimensional and three-dimensional constitutive models in the representation of the mechanical behavior of joints are presented. Future research directions are identified.

Strain in the human medial collateral ligament during valgus loading of the knee.

The medial collateral ligament is one of the most frequently injured ligaments in the knee. Although the medial collateral ligament is known to provide a primary restraint to valgus and external rotations, details regarding its precise mechanical function are unknown. In this study, strain in the medial collateral ligament of eight knees from male cadavers was measured during valgus loading. A material testing machine was used to apply 10 cycles of varus and valgus rotation to limits of +/- 10.0 N-m at flexion angles of 0 degrees, 30 degrees, 60 degrees, and 90 degrees. A three-dimensional motion analysis system measured local tissue strain on the medial collateral ligament surface within 12 regions encompassing nearly the entire medial collateral ligament surface. Results indicated that strain is significantly different in different regions over the surface of the medial collateral ligament and that this distribution of strain changes with flexion angle and with the application of a valgus torque. Strain in the posterior and central portions of the medial collateral ligament generally decreased with increasing flexion angle, whereas strain in the anterior fibers remained relatively constant with changes in flexion angle. The highest strains in the medial collateral ligament were found at full extension on the posterior side of the medial collateral ligament near the femoral insertion. These data support clinical findings that suggest the femoral insertion is the most common location for medial collateral ligament injuries.

Simple shear testing of parallel-fibered planar soft tissues.

The simple shear test may provide unique information regarding the material response of parallel-fibered soft tissues because it allows the elimination of the dominant fiber material response from the overall stresses. However, inhomogeneities in the strain field due to clamping and free edge effects have not been documented. The finite element method was used to study finite simple shear of simulated ligament material parallel to the fiber direction. The effects of aspect ratio, clamping prestrain, and bulk modulus were assessed using a transversely isotropic, hyperelastic material model. For certain geometries, there was a central area of uniform strain. An aspect ratio of 1:2 for the fiber to cross-fiber directions provided the largest region of uniform strain. The deformation was nearly isochoric for all bulk moduli indicating this test may be useful for isolating solid viscoelasticity from interstitial flow effects. Results suggest this test can be used to characterize the matrix properties for the type of materials examined in this study, and that planar measurements will suffice to characterize the strain. The test configuration may be useful for the study of matrix, fiber-matrix, and fiber-fiber material response in other types of parallel-fibered transversely isotropic soft tissues.

Strain transfer between a CPC coated strain gauge and cortical bone during bending.

The finite element method was used to simulate strain transfer from bone to a calcium phosphate ceramic (CPC) coated strain gauge. The model was constructed using gross morphometric and histological measurements obtained from previous experimental studies. Material properties were assigned based on experiments and information from the literature. Boundary conditions simulated experimental cantilever loading of rat femora. The model was validated using analytical solutions based on the theory of elasticity as well as direct comparison to experimental data obtained in a separate study. The interface between the bone and strain gauge sensing surface consisted of layers of polysulfone, polysulfone/CPC, and CPC/bone. Parameter studies examined the effect of interface thickness and modulus, gauge geometry, partial gauge debonding, and waterproofing on the strain transfer from the bone to the gauge sensing element. Results demonstrated that interface thickness and modulus have a significant effect on strain transfer. Optimal strain transfer was achieved for an interface modulus of approximately 2 GPa. Strain transfer decreased consistently with increasing interface thickness. Debonding along the lateral edges of the gauge had little effect, while debonding proximal and distal to the sensing element decreased strain transfer. A waterproofing layer decreased strain transfer, and this effect was more pronounced as the modulus or thickness of the layer increased. Based on these simulations, specific recommendations were made to optimize strain transfer between bone and CPC coated gauges for experimental studies.

Isolation and analysis of radiolabeled meningococcal endotoxin.

The Gram-negative pathogen Neisseria meningitidis, is one of the leading causes of bacterial meningitis worldwide (1). The host range for this organism is restricted to humans, where it colonizes the mucosal epithelium of the upper airway. It occasionally disseminates causing invasive disease (sepsis, disseminated intravascular coagulation [DIC], meningitis). Epidemic meningococcal meningitis is a major health problem, most notably in sub-Saharan Africa. In 1999, an outbreak of meningococcal disease spread across Guinea-Bissau, a region that is part of what is commonly called the African meningitis belt (2). There were 2,169 reported cases and 404 deaths resulting from meningococcal disease in this outbreak from Jan. 1 to April 5, 1999. Also in 1999, there were reported outbreaks in Sudan (22,000 cases and 1,600 deaths) Rwanda (29 cases and 11 deaths), Angola (253 cases and 147 deaths), Ethiopia (126 cases and 4 deaths) and Senegal (2,709 cases and 372 deaths) (2). According to the World Health Organization (WHO), each year approx 500,000 cases of meningitis and 50,000 deaths are attributable to N. meningitidis worldwide. In the United States, meningococcal disease is less common, although small outbreaks are reported each year (3).