RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Draft genomes of twelve host adapted and environmental isolates of Pseudomonas aeruginosa and their position in the core genome phylogeny.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen particularly associated with the inherited disease cystic fibrosis (CF). P. aeruginosa is well known to have a large and adaptable genome that enables it to colonise a wide range of ecological niches. Here we have used a comparative genomics approach to identify changes that occur during infection of the CF lung. We used the mucoid phenotype as an obvious marker of host adaptation and compared these genomes in order to analyse SNPs, indels and islands within near-isogenic pairs. In order to commence the correction of the natural bias towards clinical isolates in genomics studies and to widen our understanding of the genomic diversity of P. aeruginosa, we included four environmental isolates in our analysis. Our data suggests that genome plasticity plays an important role in chronic infection and that the strains sequenced in this study are representative of the two major phylogenetic groups as determined by core genome SNP analysis

A cross-sectional evaluation examining the use of the Achilles tendinopathy toolkit by physiotherapists in British Columbia, Canada

<p><b>Purpose</b>: To evaluate the awareness and use of the Achilles tendinopathy toolkit (ATT), a knowledge translation (KT) strategy supporting evidence-informed management of midportion Achilles Tendinopathy (AT), by British Columbian physiotherapists (PTs). Secondarily, to assess PTs strategies for AT management by examining the association between exploring the ATT and following best practice in clinical care as recommended by the ATT. <b>Methods</b>: Members of the Physiotherapy Association of British Columbia (BC) completed an online cross-sectional survey collecting information on demographics; awareness and exposure; perceptions, usability and applicability to clinical practice; knowledge; and attitudes. A clinical vignette assessed if respondents adhered to recommendations made by the ATT. Multi-variable logistic regression examined the association between exploring the ATT and following its recommendations. <b>Results</b>: Of 238 participants, 81% (<i>n</i> = 154) were aware of the ATT and of those 53% (<i>n</i> = 81) explored its contents. Time was the most frequent barrier. Bi-variable analyses showed those who explored the ATT had over double the odds of following the best practice (odds ratio = OR = 2.8; 95% confidence interval = 95% CI = 1.3–6.0). This did not remain significant in the final adjusted model (OR = 2.2; 95% CI = 0.9–5.4). <b>Conclusions</b>: Evaluation of KT strategies is critical. This study revealed high awareness and moderate use of the ATT. Future work should consider the impact of toolkits on patient outcomes.Implications for Rehabilitation</p><p>A toolkit is a novel knowledge translation (KT) strategy designed to provide accessibleevidence-informed resources to facilitate best practice by clinicians.</p><p>The evaluation of the Achilles tendinopathy toolkit (ATT) revealed favourable findingsregarding the impact of this KT strategy on the knowledge and attitudes of British Columbia(BC) PTs and the possibility of a positive impact on best practice in clinical care.</p><p>This research suggests toolkits are a feasible and meaningful KT strategy to provide clinicianswith valuable synthesized resources that have the potential to benefit patient outcomes.</p><p></p> <p>A toolkit is a novel knowledge translation (KT) strategy designed to provide accessibleevidence-informed resources to facilitate best practice by clinicians.</p> <p>The evaluation of the Achilles tendinopathy toolkit (ATT) revealed favourable findingsregarding the impact of this KT strategy on the knowledge and attitudes of British Columbia(BC) PTs and the possibility of a positive impact on best practice in clinical care.</p> <p>This research suggests toolkits are a feasible and meaningful KT strategy to provide clinicianswith valuable synthesized resources that have the potential to benefit patient outcomes.</p

CD169+ macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer

Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein, we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts); and targeted depletion of CD169(+) macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68(+) macrophages were consistently located within the tumour mass. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected, had varied distributions. In the immune-competent mouse model, CD169(+) macrophage ablation significantly inhibited prostate cancer-induced woven bone formation, suggesting that CD169(+) macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast, pan-phagocytic cell, but not targeted CD169(+) macrophage depletion resulted in increased tumour mass, indicating that CD169(-) macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role for macrophages in prostate cancer bone metastasis that may be therapeutically targetable to reduce the negative skeletal impacts of this malignancy, including tumour-induced bone modelling. Copyright (C) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd