Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity

Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs

Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. The customization of intrinsic cellular signaling pathways in stem cells, as demonstrated here, opens innovative possibilities for safer and more effective therapeutic approaches for a wide variety of diseases

Lessons learnt from the use of relationship-based procurement methods in Australia: clients’ perspectives

This paper aims to review the use of various construction procurement systems and present the development of Relationship-Based Procurement (RBP) Methods currently in use within the Australian construction industry. Therefore, this paper provides the historical development of procurement briefly and then focuses on the adoption of Relationship-Based Procurement (RBP) approaches in the Australian construction industry to investigate the future direction of the collaborative project procurement arrangements. Semi-structured interviews with high-level managers in the Australian state government organizations have been conducted to answer the research question. A discussion has been presented about the potential future tendency of the industry in adopting a RBP. The findings suggest that even though relationship based procurement systems offer significant benefits; they are not popular among the public sector decision makers because of inability to demonstrate Value for Money (VfM) propositions for public projects. Other reasons which may cause a move away from using RBPs in the future include the need for managers to fully engage throughout the project, and the lack of collaborative environment within the construction industry in general.

Training modalities in robot-mediated upper limb rehabilitation in stroke : A framework for classification based on a systematic review

© 2014 Basteris et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The work described in this manuscript was partially funded by the European project ‘SCRIPT’ Grant agreement no: 288698 (http://scriptproject.eu). SN has been hosted at University of Hertfordshire in a short-term scientific mission funded by the COST Action TD1006 European Network on Robotics for NeuroRehabilitationRobot-mediated post-stroke therapy for the upper-extremity dates back to the 1990s. Since then, a number of robotic devices have become commercially available. There is clear evidence that robotic interventions improve upper limb motor scores and strength, but these improvements are often not transferred to performance of activities of daily living. We wish to better understand why. Our systematic review of 74 papers focuses on the targeted stage of recovery, the part of the limb trained, the different modalities used, and the effectiveness of each. The review shows that most of the studies so far focus on training of the proximal arm for chronic stroke patients. About the training modalities, studies typically refer to active, active-assisted and passive interaction. Robot-therapy in active assisted mode was associated with consistent improvements in arm function. More specifically, the use of HRI features stressing active contribution by the patient, such as EMG-modulated forces or a pushing force in combination with spring-damper guidance, may be beneficial.Our work also highlights that current literature frequently lacks information regarding the mechanism about the physical human-robot interaction (HRI). It is often unclear how the different modalities are implemented by different research groups (using different robots and platforms). In order to have a better and more reliable evidence of usefulness for these technologies, it is recommended that the HRI is better described and documented so that work of various teams can be considered in the same group and categories, allowing to infer for more suitable approaches. We propose a framework for categorisation of HRI modalities and features that will allow comparing their therapeutic benefits.Peer reviewedFinal Published versio

Estimation of in place hydrocarbon volume in multilayered reservoirs using deterministic and probabilistic approaches

International audienceThis paper presents the results of the calculation techniques used for estimation of hydrocarbon initially in place for a multilayered gas reservoir located in the Persian Gulf via two methodologies. The porosity, water saturation, and net pay raw datasets for six wells enclosed within the studied area are thoroughly examined and fed to the deterministic and probabilistic calculation algorithms and the results are compared. In order to include the probable effects of the uncertainties associated with reservoir characterization, two distinct methodologies are developed and incorporated in both types of the calculation processes. In the first methodology, total hydrocarbon volume is calculated in one stage, while in another, hydrocarbon volume estimation have been carried out separately in each producing layer; then, summing them to estimate total hydrocarbon volume. The prominent conclusion of this research indicates that the second developed method in both deterministic and probabilistic conditions presentsmore reliable results for hydrocarbon volume estimation

Meniscus-derived matrix scafolds promote the integrative repair of meniscal defects

Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair and improve meniscus function are needed. The objective of this study was to generate porcine meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting meniscus repair via migration of endogenous meniscus cells from the surrounding meniscus or exogenously seeded human bone marrow-derived mesenchymal stem cells (MSCs). Both endogenous meniscal cells and MSCs infiltrated the MDM scaffolds. In the absence of exogenous cells, the 8% MDM scaffolds promoted the integrative repair of an in vitro meniscal defect. Dehydrothermal crosslinking and concentration of the MDM influenced the biochemical content and shear strength of repair, demonstrating that the MDM can be tailored to promote tissue repair. These findings indicate that native meniscus cells can enhance meniscus healing if a scaffold is provided that promotes cellular infiltration and tissue growth. The high affinity of cells for the MDM and the ability to remodel the scaffold reveals the potential of MDM to integrate with native meniscal tissue to promote long-term repair without necessarily requiring exogenous cells

FORMULATION OF NANOPARTICLES OF ANTI-MIGRAINE DRUGS TRIPTANS BY COACERVATION METHOD

  Objective: Triptans are effective medicines used to treat migraine and certain other headaches. This study has been conducted to prepared nanoparticles (NPs) of triptans by coacervation technique using a different drug to polymer ratios and evaluated.Methods: Polymers such as albumin and gelatin and cross-linking agent were used at different levels to prepare triptan NPs with high entrapment efficiency (EE) and low particle size (PS). Completion of the reaction was confirmed by infrared spectra. NPs were evaluated for shape and surface morphology, polydispersity index, zeta potential, EE, and PS distribution.Results: Among all the formulation, AA5 formulation of triptan-loaded albumin NPs (ANPs) has small PS and high EE.Conclusion: In this study, we have found that the ANPs in the presence of 4% glutaraldehyde as a cross-linking agent could be used as a delivery vehicle of triptans