Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which - once applied to human neutrophils - attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor-deficient mice termed ALX/fpr2/3-/- . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA

Non-western contexts: the invisible half

Like many other disciplines within the broad area of social sciences (e.g., anthropology, gender studies, psychology, sociology, etc.), consumer research is also highly navigated by scholars from Western countries. This, however, does not mean, by any means, that consumer research is devoted to studying Western contexts only. As evident from the ever-increasing number of regional conferences (e.g., Asia-Pacific and Latin American conferences of the Association for Consumer Research) and non-Western students' enrolment in doctoral programs at Western universities, there are many more researchers (from non-Western countries) who are entering the field and enriching it by their colourful contributions. Yet, given the low number of publications on consumer research in non-Western contexts, it seems that our current knowledge in these societies has a long way to go to flourish. More specifically, and in the domain of consumption culture research, this gap is even further widened by the fact that the culture of consumption in such contexts is largely interpreted with reference to the 'grand narratives' of Western scholars (e.g., Foucault, Mafessoli, Bourdieu, Deleuze, Baudrillard, Nietzsche, Durkheim, Derrida, etc.). Therefore, from an ontological perspective, it seems that our existing knowledge about non-Western societies lies heavily on the 'theoretical structures' that are 'constructed' by Western philosophy as a set of ideas, beliefs, and practices (Said, 1978). As Belk (1995) reminds us, consumption culture always existed in all human societies. What makes contemporary societies different from that of our predecessors' is not the fact that consumption culture did not exist in those societies, but that consumption culture has become a prevailing feature in modern society (Slater, 1997; Lury, 1996; Fırat and Venkatesh, 1995; McCracken, 1988). Therefore, the nature and dynamics of consumption culture in each society should be studied not only against the sociocultural, historical, and economic background of a given context (Western or non-Western) but also with reference to the philosophical and epistemological viewpoints that analyse and interpret cultural practices of that society from within that culture. Addressing such issues, this paper discusses some of the key reasons for lack of theory development in the field from non-western contexts. The paper invites scholars in non-Western contexts to introduce the less articulated, and sometime hidden, body of knowledge from their own contexts into the field of marketing in general and consumer research in particular

CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses

CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response

Estimating the mode I through-thickness intralaminar R-curve of unidirectional carbon fibre-reinforced polymers using a micromechanics framework combined with the size effect method

A three-dimensional micromechanics framework is developed to estimate the mode I through-thickness intralaminar crack resistance curve of unidirectional carbon fibre-reinforced polymers. Finite element models of geometrically-scaled single edge notch tension specimens were generated. These were modelled following a combined micro-/meso-scale approach, where the region at the vicinity of the crack tip describes the microstructure of the material, while the regions far from the crack tip represent the mesoscopic linear-elastic behaviour of the composite. This work presents a novel methodology to estimate fracture properties of composite materials by combining computational micromechanics with the size effect method. The size effect law of the material, and consequently the crack resistance curve, are estimated through the numerically calculated peak stresses. In-depth parametric analyses, which are hard to conduct empirically, are undertaken, allowing for quantitative and qualitative comparisons to be successfully made with experimental and numerical observations taken from literature

The international entrepreneurial firm's social networks

This paper investigates theoretically the importance and impact of the international entrepreneurial firms’ (IEFs) social networks on selected firms’ strategies. We focus specifically on some core attributes of IEFs and the impact of social networks on such strategies as the choice of the foreign markets to operate and the foreign entry modes. The social networks are a major driver of the internationalization from inception and help in overcoming a variety of physical and social resource limitations as well as transactional hazards. We conclude that it is likely that both some fundamental characteristics of the IEFs and those of the foreign markets entered account for these firms reliance on their social networks

Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis.

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA

Compassionate pedagogy: the ethics of care in early childhood professionalism

This paper builds upon an earlier attempt (Taggart, 2011) to articulate a rationale for professional training in early childhood education and care (ECEC) which is ethical as opposed to one which is purely instrumental or rooted in a patriarchal notion of women’s supposed unique suitability. The argument proposes that a feminist approach to ethics, as both socially critical and psychologically affective or flexible, has a particular relevance to professional identity in ECEC. In particular, compassion, as a concept which has both sociological and psychological connotations, foregrounds the ethical dimension of the work whilst overcoming false dichotomies between discourses of ‘children’s rights’ and ‘care’. The implications for the training and professional identity of practitioners are discussed

Beyond buying: Extending the concept of acquisition in consumption

The consumption process constitutes a sequence of acquisition, use/consumption, and disposal. Over the last two decades, acquisition has transformed due to digitization and sharing economy innovations. Consumers obtain goods and services through several practices beyond buying, including renting, sharing, streaming, borrowing, and gifting. Access constitutes equal options to ownership, and non-market-mediated exchanges have become alternatives to market exchanges. While research has begun to study these practices, it remains fragmented, and we lack a unifying conceptual framework of acquisition. This gap risks marketers overlooking the acquisition phase, the essential first touchpoint in the customer journey. We develop a new conceptual acquisition framework organized by the levels of ownership transfer and market mediation. It distinguishes four acquisition modes: market-mediated ownership, market-mediated access, non-market-mediated ownership, and non-market-mediated access. We extend the acquisition concept beyond buying and market exchange, contributing to research on access, sharing, and customer journey, and we advance a future research agenda

Young children and their conduct of everyday life

The article presents findings from a practice research project dealing with the everyday life of 0-2 year olds across family and different day-care settings. From a critical psychological perspective, it explores three related issues: Young children's conduct of everyday life in and across different institutional settings; professional pedagogical work related to supporting children's conduct of everyday life, and finally, the restricted political and bureaucratic conditions for exactly these forms of pedagogical practice. The article addresses the theoretical challenge of understanding children through their conduct of everyday life in the field of tension between being someone who is dependent on others, being taken care of and arranged for - and, at the same time, someone who is actively participating, arranging and contributing to the reproduction and change of the collective life conditions in the social practice of day-care. These compound processes include the professional's complex efforts to support the many children's personal conduct of everyday life in and across their different life arenas, involving ongoing situated and sensitive exploration of children's perspectives through observations, conversations and collaborative processes with the different children, colleagues, families in the day-care environment. However, at the same time, exactly these situated explorative processes tend to be unheeded as professional in the more explicit professional explanations of problems in day-care. Through a discussion of this apparent contradiction and the conditions for developing a more situated approach, the article aims to contribute to the current professional and political discussions about day-care practice for the youngest children.</p

A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA

Cusanuswerk, who supported D.F. with a stipend. J.D. is funded by European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant no: 677542) and the Barts Charity (grant no: MGU0343) to J.D. J.D. is also supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant 107613/Z/15/Z)