General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Differential glucocorticoid metabolism in patients with persistent versus resolving inflammatory arthritis

Introduction: Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. In the inflamed synovium, cortisol is generated from cortisone by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. The objective of this study was to determine the role of endogenous glucocorticoid metabolism in the development of persistent inflammatory arthritis. Methods: Urine samples were collected from patients with early arthritis (symptoms ≤12 weeks duration) whose final diagnostic outcomes were established after clinical follow-up and from patients with established rheumatoid arthritis (RA). All patients were free of disease-modifying anti-rheumatic drugs at the time of sample collection. Systemic measures of glucocorticoid metabolism were assessed in the urine samples by gas chromatography/mass spectrometry. Clinical data including CRP and ESR were also collected at baseline. Results: Systemic measures of 11β-HSD1 activity were significantly higher in patients with early arthritis whose disease went on to persist, and also in the subgroup of patients with persistent disease who developed RA, when compared with patients whose synovitis resolved over time. We observed a significant positive correlation between systemic 11β-HSD1 activity and ESR/CRP in patients with established RA but not in any of the early arthritis patients group. Conclusions: The present study demonstrates that patients with a new onset of synovitis whose disease subsequently resolved had significantly lower levels of systemic 11β-HSD1 activity when compared with patients whose synovitis developed into RA or other forms of persistent arthritis. Low absolute levels of 11β-HSD1 activity do not therefore appear to be a major contributor to the development of RA and it is possible that a high total body 11β-HSD1 activity during early arthritis may reduce the probability of disease resolution

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u

Cognitive Aging in Zebrafish

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline

Giving risk management culture a role in strategic planning

WOS: 000413939000023Strategically planned and implemented risk management paves the way for competitive advantage and a decisive edge for global financial institutions. The importance of risk management becomes more evident in financial instability periods. The failure of global financial institutions in the recent financial crisis revealed that firms with strong risk management and culture were more prepared and economically less damaged. As financial institutions have been criticized severely about risk management practices, it also becomes clear that most financial institutions have difficulties in developing a risk management culture. To have a clear understanding of risk management culture, the chapter aims to highlight a need to extend our understanding of risk management culture and how it can find a voice in the strategic planning of global financial institutions

Gas-cushioned droplet impacts with a thin layer of porous media

The authors are grateful to Dr. Manish Tiwari for introducing them to experiments involving droplet impacts with textured substrates. PDH is grateful for the use of the Maxwell High-Performance Computing Cluster of the University of Aberdeen IT Service. RP is grateful for the use of the High-Performance Computing Cluster supported by the Research and Specialist Computing Support service at the University of East Anglia.Peer reviewedPostprin

Adherence to colorectal cancer screening guidelines in Canada

<p>Abstract</p> <p>Background</p> <p>To identify correlates of adherence to colorectal cancer (CRC) screening guidelines in average-risk Canadians.</p> <p>Methods</p> <p>2003 Canadian Community Health Survey Cycle 2.1 respondents who were at least 50 years old, without past or present CRC and living in Ontario, Newfoundland, Saskatchewan, and British Columbia were included. Outcomes, defined according to current CRC screening guidelines, included adherence to: i) fecal occult blood test (FOBT) (in prior 2 years), ii) endoscopy (colonoscopy/sigmoidoscopy) (prior 10 years), and iii) adherence to CRC screening guidelines, defined as either (i) or (ii). Generalized estimating equations regression was employed to identify correlates of the study outcomes.</p> <p>Results</p> <p>Of the 17,498 respondents, 70% were non-adherent CRC screening to guidelines. Specifically, 85% and 79% were non-adherent to FOBT and endoscopy, respectively. Correlates for all outcomes were: having a regular physician (OR = (i) 2.68; (ii) 1.91; (iii) 2.39), getting a flu shot (OR = (i) 1.59; (ii) 1.51; (iii) 1.55), and having a chronic condition (OR = (i) 1.32; (ii) 1.48; (iii) 1.43). Greater physical activity, higher consumption of fruits and vegetables and smoking cessation were each associated with at least 1 outcome. Self-perceived stress was modestly associated with increased odds of adherence to endoscopy and to CRC screening guidelines (OR = (ii) 1.07; (iii) 1.06, respectively).</p> <p>Conclusion</p> <p>Healthy lifestyle behaviors and factors that motivate people to seek health care were associated with adherence, implying that invitations for CRC screening should come from sources that are independent of physicians, such as the government, in order to reduce disparities in CRC screening.</p

Can houseplants improve indoor air quality by removing CO2 and increasing relative humidity?

High indoor CO2 concentrations and low relative humidity (RH) create an array of well-documented human health issues. Therefore, assessing houseplants’ potential as a low-cost approach to CO2 removal and increasing RH is important. We investigated how environmental factors such as ’dry’ ( 0.30 m3 m-3) growing substrates, and indoor light levels (‘low’ 10 µmol m-2 s-1, ‘high’ 50 µmol m-2 s-1 and ‘very high’ 300 µmol m-2 s-1), influence the plants’ net CO2 assimilation (‘A’) and water-vapour loss. Seven common houseplant taxa – representing a variety of leaf types, metabolisms and sizes – were studied for their ability to assimilate CO2 across a range of indoor light levels. Additionally, to assess the plants’ potential contribution to RH increase, the plants’ evapo-transpiration (ET) was measured. At typical ‘low’ indoor light levels ‘A’ rates were generally low (< 3.9 mg hr-1). Differences between ‘dry’ and ’wet’ plants at typical indoor light levels were negligible in terms of room-level impact. Light compensation points (i.e. light levels at which plants have positive ‘A’) were in the typical indoor light range (1-50 µmol m-2 s-1) only for two studied Spathiphyllum wallisii cultivars and Hedera helix; these plants would thus provide the best CO2 removal indoors. Additionally, increasing indoor light levels to 300 µmol m-2 s-1 would, in most species, significantly increase their potential to assimilate CO2. Species which assimilated the most CO2 also contributed most to increasing RH

Multiparameter Phospho-Flow Analysis of Lymphocytes in Early Rheumatoid Arthritis: Implications for Diagnosis and Monitoring Drug Therapy

The precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying diagnosis and therapy. Additionally, there are currently no established means to predict clinical responsiveness to therapy. Immune cell activation is a critical component therefore we examined the cellular activation of peripheral blood mononuclear cells (PBMCs) in the early stages of RA, in order to develop a novel diagnostic modality.PBMCs were isolated from individuals diagnosed with early RA (ERA) (n = 38), longstanding RA (n = 10), osteoarthritis (OA) (n = 19) and from healthy individuals (n = 10). PBMCs were examined for activation of 15 signaling effectors, using phosphorylation status as a measure of activation in immunophenotyped cells, by flow cytometry (phospho-flow). CD3+CD4+, CD3+CD8+ and CD20+ cells isolated from patients with ERA, RA and OA exhibited activation of multiple phospho-epitopes. ERA patient PBMCs showed a bias towards phosphorylation-activation in the CD4+ and CD20+ compartments compared to OA PBMCs, where phospho-activation was primarily observed in CD8+ cells. The ratio of phospho (p)-AKT/p-p38 was significantly elevated in patients with ERA and may have diagnostic potential. The mean fluorescent intensity (MFI) levels for p-AKT and p-H3 in CD4+, CD8+ and CD20+ T cells correlated directly with physician global assessment scores (MDGA) and DAS (disease activity score). Stratification by medications revealed that patients receiving leflunomide, systemic steroids or anti-TNF therapy had significant reductions in phospho-specific activation compared with patients not receiving these therapies. Correlative trends between medication-associated reductions in the levels of phosphorylation of specific signaling effectors and lower disease activity were observed.Phospho-flow analysis identified phosphorylation-activation of specific signaling effectors in the PB from patients with ERA. Notably, phosphorylation of these signaling effectors did not distinguish ERA from late RA, suggesting that the activation status of discrete cell populations is already established early in disease. However, when the ratio of MFI values for p-AKT and p-p38 is >1.5, there is a high likelihood of having a diagnosis of RA. Our results suggest that longitudinal sampling of patients undergoing therapy may result in phospho-signatures that are predictive of drug responsiveness