The disease modifying osteoarthritis drug diacerein is able to antagonize pro inflammatory state of chondrocytes under mild mechanical stimuli

SummaryObjectiveTo investigate the combination of mild mechanical stimuli and a disease modifying osteoarthritis drug (DMOAD) in inflammatory activated chondrocytes and to study the combination of drug and mechanical tension on the cellular level as a model for an integrated biophysical approach for osteoarthritis (OA) treatments.MethodsInterleukin-1beta (IL-1β) stimulated C28/I2 cells underwent mild mechanically treatment while cultured in the presence of the DMOAD diacerein. The pharmacological input of diacerein was evaluated by cell viability and cell proliferation measurements. Inflammation and treatment induced changes in key regulatory proteins and components of the extracellular matrix (ECM) were characterized by quantitative real-time PCR (qPCR). The effects on metalloproteinase-1 (MMP-1) activity and glycosaminoglycan (GAG) concentration in cell supernatants of treated cells were investigated.ResultsC28/I2 cells demonstrated significant changes in expression of inflammatory and cartilage destructive proteins in response to IL-1β stimulation. The chondroprotective action of diacerein in mechanically stimulated cells was mediated by a decrease in interleukin-8 (IL-8), fibronectin-1 (FN-1), collagen type I (Col 1) and MMP-1 expression levels, respectively. Augmented expression of interleukin-6 receptor (IL-6R) and the fibroblast growth factor receptors (FGFRs) by diacerein was not abolished by mechanical treatment. The observed effects were accompanied by a reduced cell proliferation rate, attenuated cell viability and extenuated MMP-1 activity.ConclusionDiacerein diversely regulates the expression of main regulatory proteins as well as components important to regenerate and set up ECM. Mechanical stimulation does not negatively influence the chondroprotective effect induced by diacerein treatment in immortalized human C28/I2 chondrocytes

Chronic low back pain: a prospective study with 4 to 15 years follow-up after a multidisciplinary biopsychosocial rehabilitation program

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation (MBR) in patients with chronic low back pain (CLBP) is superior to less intensive treatments for at least one year, but the long-term course of the disease is largely unknown. The primary aim of this study was to describe the long-term course of an MBR in relation to pain, disability, and quality of life from the beginning of an MBR to between 4 to 15 years after participation. The secondary aim was to explore the long-term course of an MBR in relation to physiological outcomes of functioning. METHODS: This was a observational study conducted at a university hospital. The cohort consisted of participants of a 3-week, CLBP-specific MBR program between August 2001 and January 2013. The North American Spine Society questionnaire (NASS) pain and disability scale was the primary patient -reported outcome measure (PROM). The NASS neurogenic symptoms scale and the Short-Form 36 (SF-36) health survey were secondary PROMs. Patients were assessed before entry to the MBR (T0), at entry (T1), at discharge (T2) and 4 to 15 years after discharge (T3). Effects were quantified by effect size (ES). Score differences were tested for significance using parametric or non-parametric tests and linear mixed models. RESULTS: Of 299 consecutive patients from the MBR program, 229 could be contacted. Of these, 84 declined participation, five did not meet the inclusion criteria, and 26 had incomplete data. Thus, 114 patients were included. The mean follow-up time was 9.2 years. At T3, patients exhibited beneficial effects for NASS pain and disability with a moderate ES (ES = 0.63; p < 0.001). The NASS neurogenic symptoms scale was stable. The SF-36 scales showed an improvement in the bodily pain domain (ES = 1.02; p < 0.001), but no significant changes for physical functioning, physical role, general health, vitality, social functioning, emotional role, or mental health. The physical health component summary was improved (ES = 0.40, p = 0.002), and the mental health summary was unchanged. The linear mixed model analysis confirmed improvements in pain and disability between T1 and T3 (p = 0.010). CONCLUSIONS: The results of this study suggest that there is a long-term benefit of MBR participation in patients with CLBP

Proving equivalence between imperative and MapReduce implementations using program transformations

Distributed programs are often formulated in popular functional frameworks like MapReduce, Spark and Thrill, but writing efficient algorithms for such frameworks is usually a non-trivial task. As the costs of running faulty algorithms at scale can be severe, it is highly desirable to verify their correctness. We propose to employ existing imperative reference implementations as specifications for MapReduce implementations. To this end, we present a novel verification approach in which equivalence between an imperative and a MapReduce implementation is established by a series of program transformations. In this paper, we present how the equivalence framework can be used to prove equivalence between an imperative implementation of the PageRank algorithm and its MapReduce variant. The eight individual transformation steps are individually presented and explained

Chiral extrapolation of lattice moments of proton quark distributions

We present the resolution of a long-standing discrepancy between the moments of parton distributions calculated from lattice QCD and their experimental values. We propose a simple extrapolation formula for the moments of the nonsinglet quark distribution u-d, as a function of quark mass, which embodies the general constraints imposed by the chiral symmetry of QCD. The inclusion of the leading nonanalytic behavior leads to an excellent description of both the lattice data and the experimental values of the moments.Comment: 9 pages, 1 figure, to appear in Physical Review Letter

Ethnic In-Group Favoritism Among Minority and Majority Groups: Testing the Self-Esteem Hypothesis Among Preadolescents

The self-esteem hypothesis in intergroup relations, as proposed by social identity theory (SIT), states that successful intergroup discrimination enhances momentary collective self-esteem. This hypothesis is a source of continuing controversy. Furthermore, although SIT is increasingly used to account for children’s group attitudes, few studies have examined the hypothesis among children. In addition, the hypothesis’s generality makes it important to study among children from different ethnic groups. The present study, conducted among Dutch and Turkish preadolescents, examined momentary collective self-feelings as a consequence of ethnic group evaluations. The results tended to support the self-esteem hypothesis. In-group favoritism was found to have a self-enhancing effect among participants high in ethnic identification. This result was found for ethnic majority (Dutch) and minority (Turkish) participants.

Dynamic splinting home therapy for toe walking: a case report

Serial casting is frequently prescribed for toe-walking but that does not allow continued physical therapy (PT). This report described a child and family who chose dynamic splinting (DS) with concurrent PT for treatment. The patient presented with right hemiparesis; below average motor skills and a gait pattern of toe contact (without ankle foot orthosis). Four months of PT plus 6 hours/night of DS as home therapy, the patient's passive dorsiflexion increased 14° and she gained the ability to walk in "flat foot" contact without the Ankle Foot Orthosis. This concurrent treatment achieved improved gait pattern and strength training not possible with casting

Nonperturbative versus perturbative effects in generalized parton distributions

Generalized parton distributions (GPDs) are studied at the hadronic (nonperturbative) scale within different assumptions based on a relativistic constituent quark model. In particular, by means of a meson-cloud model we investigate the role of nonperturbative antiquark degrees of freedom and the valence quark contribution. A QCD evolution of the obtained GPDs is used to add perturbative effects and to investigate the GPDs' sensitivity to the nonperturbative ingredients of the calculation at larger (experimental) scale.Comment: 17 pages, 10 figures; submitted to Phys. Rev.

Universality for 2D Wedge Wetting

We study 2D wedge wetting using a continuum interfacial Hamiltonian model which is solved by transfer-matrix methods. For arbitrary binding potentials, we are able to exactly calculate the wedge free-energy and interface height distribution function and, thus, can completely classify all types of critical behaviour. We show that critical filling is characterized by strongly universal fluctuation dominated critical exponents, whilst complete filling is determined by the geometry rather than fluctuation effects. Related phenomena for interface depinning from defect lines in the bulk are also considered.Comment: 4 pages, 1 figur