NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

OBJECTIVE: This study aimed to examine the temporal activation of NF-κB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA. METHOD: Following knee injury NF-κB activity was assessed longitudinally via in vivo imaging in FVB. Cg-Tg (HIV-EGFP,luc)8Tsb/J mice. Measures of pain-related sensitivity and behavior were also assessed longitudinally for 16 weeks. Additionally, we antagonized NF-κB signaling via intra-articular delivery of an IκB kinase two antagonist to understand how local NF-κB inhibition might alter disease progression. RESULTS: Following joint injury NF-κB signaling within the knee joint was transiently increased and peaked on day 3 with an estimated 1.35 p/s/cm CONCLUSION: These findings underscore the development of behavioral changes in this non-invasive loading model of PTOA and their relationships to NF-κB activation and pathology. They also highlight the potential chondroprotective effects of NF-κB inhibition shortly following joint injury despite limitations in preventing the long-term development of joint degeneration in this model of PTOA

A atitude do educador de infância e a participação da criança como referenciais de qualidade em educação

Neste artigo, fundamentado em dois estudos de caso em jardim de infância, refletiu- -se sobre como e com quais ferramentas de apoio se pode avaliar e promover qualidade e intervenção educativa adequada nos contextos. Selecionou-se um grupo de crianças (entre 3 e 6 anos) e desenvolveram-se estratégias com a finalidade de escutar e compreender o modo como elas participam. Ainda, em diversos tempos da rotina de cada contexto, identificaram-se interações e atitudes do educador, analisando-se o respetivo impacto no nível da participação das crianças. Os resultados revelaram que, quando as crianças desenvolvem um sentimento de pertença ao contexto e lhes são oferecidas oportunidades de participação, mais facilmente se envolvem, revelam bem-estar emocional e motivação para aprender, explorar e participar nos processos de tomada de decisão. A escuta ativa, o questionamento e o encorajamento do diálogo assumem-se, por parte do adulto, competências essenciais para a qualidade da intervenção educativa.This paper, based on two case studies in a kindergarten context, describes a reflection on the most appropriate method and tools for the assessment and promotion of quality and context intervention. A group of children (between 3 and 6 years old) was selected and strategies were developed in order to listen to the children’s voices and understand how they were participating. Moreover, in different routine times within each context, interactions and attitudes of educators were identified, with the corresponding analysis of the impact on children’s participation. The results revealed that when children develop a sense of belonging in the context and they are offered opportunities to participate, they more easily get engaged, reveal emotional wellbeing and motivation to learn, explore and participate in decision-making processes. For the adult, active listening, questioning and encouragement of dialogue appear as essential skills to promote quality in educational intervention.En el presente artículo, basado en dos estudios de caso en un jardín de infancia, se reflexionó sobre cómo y con qué herramientas de apoyo se puede evaluar y promover calidad e intervención educativa apropiada en los contextos. Se seleccionó un grupo de niños (entre los 3 y 6 años de edad) y se desarrollaron estrategias con la finalidad de escuchary comprender el modo como dichos niños participan. Además, en diversos momentos de la rutina de cada contexto, se identificaron interacciones y actitudes del educador, analizando el respectivo impacto en la participación de los infantes. Los resultados revelaron que, cuando los niños desarrollan un sentido de pertenencia al contexto y se les ofrece la oportunidad de participar, más fácilmente se envuelven, revelan bienestar emocional y motivación para aprender, explorar y participar en la toma de decisiones. La escucha activa, el cuestionar y fomentar el diálogo constituyen, para el adulto, competencias esenciales para la calidad de la intervención educativa

Three-dimensional culture of human meniscal cells: Extracellular matrix and proteoglycan production

<p>Abstract</p> <p>Background</p> <p>The meniscus is a complex tissue whose cell biology has only recently begun to be explored. Published models rely upon initial culture in the presence of added growth factors. The aim of this study was to test a three-dimensional (3D) collagen sponge microenvironment (without added growth factors) for its ability to provide a microenvironment supportive for meniscal cell extracellular matrix (ECM) production, and to test the responsiveness of cells cultured in this manner to transforming growth factor-β (TGF-β).</p> <p>Methods</p> <p>Experimental studies were approved prospectively by the authors' Human Subjects Institutional Review Board. Human meniscal cells were isolated from surgical specimens, established in monolayer culture, seeded into a 3D scaffold, and cell morphology and extracellular matrix components (ECM) evaluated either under control condition or with addition of TGF-β. Outcome variables were evaluation of cultured cell morphology, quantitative measurement of total sulfated proteoglycan production, and immunohistochemical study of the ECM components chondroitin sulfate, keratan sulfate, and types I and II collagen.</p> <p>Result and Conclusion</p> <p>Meniscal cells attached well within the 3D microenvironment and expanded with culture time. The 3D microenvironment was permissive for production of chondroitin sulfate, types I and II collagen, and to a lesser degree keratan sulfate. This microenvironment was also permissive for growth factor responsiveness, as indicated by a significant increase in proteoglycan production when cells were exposed to TGF-β (2.48 μg/ml ± 1.00, mean ± S.D., vs control levels of 1.58 ± 0.79, p < 0.0001). Knowledge of how culture microenvironments influence meniscal cell ECM production is important; the collagen sponge culture methodology provides a useful in vitro tool for study of meniscal cell biology.</p

Thomas-Fermi Calculation of the Interlayer Force in Graphite

A model of a graphite crystal is proposed in which planar layers of positive charge are considered instead of the point charges of nuclei. The interlayer electronic density is calculated integrating both the Thomas-Fermi and the Thomas-Fermi-Dirac equations. From these densities, the total energy of the electrons is calculated including corrections for inhomogeneity in the form of Weizsäcker and Kirzhnits. The influence of the different corrections is studied with the result that the best method is to calculate the density from the Thomas-Fermi-Dirac equation and to take into account the inhomogeneity corrections in the form of Kirzhnits

Altered Trabecular Bone Structure and Delayed Cartilage Degeneration in the Knees of Collagen VI Null Mice

Mutation or loss of collagen VI has been linked to a variety of musculoskeletal abnormalities, particularly muscular dystrophies, tissue ossification and/or fibrosis, and hip osteoarthritis. However, the role of collagen VI in bone and cartilage structure and function in the knee is unknown. In this study, we examined the role of collagen VI in the morphology and physical properties of bone and cartilage in the knee joint of Col6a1−/− mice by micro-computed tomography (microCT), histology, atomic force microscopy (AFM), and scanning microphotolysis (SCAMP). Col6a1−/− mice showed significant differences in trabecular bone structure, with lower bone volume, connectivity density, trabecular number, and trabecular thickness but higher structure model index and trabecular separation compared to Col6a1+/+ mice. Subchondral bone thickness and mineral content increased significantly with age in Col6a1+/+ mice, but not in Col6a1−/− mice. Col6a1−/− mice had lower cartilage degradation scores, but developed early, severe osteophytes compared to Col6a1+/+mice. In both groups, cartilage roughness increased with age, but neither the frictional coefficient nor compressive modulus of the cartilage changed with age or genotype, as measured by AFM. Cartilage diffusivity, measured via SCAMP, varied minimally with age or genotype. The absence of type VI collagen has profound effects on knee joint structure and morphometry, yet minimal influences on the physical properties of the cartilage. Together with previous studies showing accelerated hip osteoarthritis in Col6a1−/− mice, these findings suggest different roles for collagen VI at different sites in the body, consistent with clinical data

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: Assessment of environmental exposures

The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3–4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set

Simulated-Physiological Loading Conditions Preserve Biological and Mechanical Properties of Caprine Lumbar Intervertebral Discs in Ex Vivo Culture

Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions