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

An Integrated Literature Review of Time-on-Task Effects With a Pragmatic Framework for Understanding and Improving Decision-Making in Multidisciplinary Oncology Team Meetings

Multidisciplinary oncology team meetings (MDMs) or tumor boards, like other MDMs in healthcare, facilitate the incorporation of diverse clinical expertise into treatment planning for patients. Decision-making (DM) in relation to treatment planning in MDMs is carried out repeatedly until all patients put forward for discussion have been reviewed. Despite continuing financial pressure and staff shortages, the workload of cancer MDMs, and therefore meeting duration continue to increase (up to 5 h) with patients often receiving less than 2 min of team input. This begs the question as to whether the current set-up is conducive to achieve optimal DM, which these multi-specialty teams were set out to achieve in the first place. Much of what it is known, however, about the effects of prolonged cognitive activity comes from various subfields of science, leaving a gap in applied knowledge relating to complex healthcare environments. The objective of this review was thus to synthesize theory, evidence and clinical practice in order to bring the current understanding of prolonged, repeated DM into the context of cancer MDMs. We explore how and why time spent on a task affects performance in such settings, and what strategies can be employed by cancer teams to counteract negative effects and improve quality and safety. In the process, we propose a pragmatic framework of repeated DM that encompasses the strength, the process and the cost-benefit models of self-control as applied to real-world contexts of cancer MDMs. We also highlight promising research avenues for closing the research-to-practice gap. Theoretical and empirical evidence reviewed in this paper suggests that over prolonged time spent on a task, repeated DM is cognitively taxing, leading to performance detriments. This deterioration is associated with various cognitive-behavioral pitfalls, including decreased attentional capacity and reduced ability to effectively evaluate choices, as well as less analytical DM and increased reliance on heuristics. As a short to medium term improvement for ensuring safety, consistently high quality of care for all patients, and the clinician wellbeing, future research and interventions in cancer MDMs should address time-on-task effects with a combination of evidence-based cognitive strategies. We propose in this review multiple measures that range from food intake, short breaks, rewards, and mental exercises. As a long term imperative, however, capacity within cancer services needs to be reviewed as well as how best to plan workforce development and service delivery models to achieve population coverage whilst maintaining safety and quality of care. Hence the performance detriments that arise in healthcare workers as a result of the intensity (time spent on a task) and complexity of the workload require not only more research, but also wider regulatory focus and recognition

Nuclear Shadowing and the Optics of Hadronic Fluctuations

A coordinate space description of shadowing in deep-inelastic lepton-nucleus scattering is presented. The picture in the laboratory frame is that of quark-gluon fluctuations of the high-energy virtual photon, propagating coherently over large light-cone distances in the nuclear medium. We discuss the detailed dependence of the coherence effects on the invariant mass of the fluctuation. We comment on the issue of possible saturation in the shadowing effects at very small Bjorken-$x$.Comment: 11 pages, 5 figure

Nucleon Structure Functions at Moderate Q**2: Relativistic Constituent Quarks and Spectator Mass Spectrum

We present a model description of the nucleon valence structure function applicable over the entire region of the Bjorken variable x, and above moderate values of Q**2 (> 1 GeV**2). We stress the importance of describing the complete spectrum of intermediate states which are spectator to the deep-inelastic collision. At a scale of 1 GeV**2 the relevant degrees of freedom are constituent quarks and pions. The large-x region is then described in terms of scattering from constituent quarks in the nucleon, while the dressing of constituent quarks by pions plays an important role at intermediate x values. The correct small-x behavior, which is necessary for the proper normalization of the valence distributions, is guaranteed by modeling the asymptotic spectator mass spectrum according to Regge phenomenology.Comment: 44 pages RevTeX, 9 uuencoded figures, accepted for publication in Nucl. Phys.

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

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