Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs and infliximab

Objective: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naive rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-alpha (TNF-alpha) is involved in these effects. Method: Ninety-nine patients with early, DMARD-naive RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate, radiographs were scored with the modified Sharp-van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. Results: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-alpha production in human macrophages, indicating a possible connection between resistin and TNF-alpha. Conclusion: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-alpha antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients.Peer reviewe

Bearings in Hip Arthroplasty:Joint Registries vs Precision Medicine: Review Article

Background: Precision medicine has been adopted in a range of clinical settings where omics data have led to greater characterisation of disease and stratification of patients into subcategories of phenotypes and pathologies. However, in orthopaedics, precision medicine lags behind other disciplines such as cancer. Joint registries have now amassed a huge body of data pertaining to implant performance which can be broken down into performance statistics for different material types in different cohorts of patients. The National Joint Registry of England, Wales and Northern Ireland (NJR) is now one of the largest datasets available. Other registries such as those from Sweden and Australia however contain longer follow-up. Together, these registries can provide a wealth of informative for the orthopaedics community when considering which implant to give to any particular patient. Questions/Purposes: We aim to explore the benefits of combining multiple large data streams including joint registries, published data on osteoarthritis (OA) pathogenesis and pathology and data concerning performance of each implant material combination in terms of biocompatibility. We believe that this analysis will provide a comprehensive overview of implant performance hopefully aiding surgeons in making more informed choices about which implant should be used in which patient. Methods: Data from three joint registries were combined with established literature to highlight the heterogeneity of OA disease and the different clinical outcomes following arthroplasty with a range of material types. Results: This review confirms that joint registries are unable to consider differences in arthritis presentation or underlying drivers of pathology. OA is now recognised to present with varying pathology with differing morbidity in different patient populations. Equally, just as OA is a heterogeneous disease, there are disparate responses to wear debris from different material combinations used in joint replacement surgery. This has been highlighted by recent high-profile scrutiny of early failure of metal-on-metal total hip replacement (THR) implants. Conclusions: Bringing together data from joint registries, biomarker analysis, phenotyping of OA patients and knowledge of how different patients respond to implant debris will lead to a truly personalised approach to treating OA patients, ensuring that the correct implant is given to the correct patient at the correct time

What drives idiosyncratic volatility over time?

We document the patterns of market-wide and firm-specific volatility in the Portuguese stock market over the 1991–2005 period and test several explanations for the behavior of firm-level idiosyncratic volatility. Unlike previous studies we find no evidence of a statistically significant rise in firm- specific volatility. On the contrary, the ratio of firm-specific risk to total risk slightly decreases. We show that this result stems from new listings of large privatized companies that display lower firm-specific risk. Our findings are consistent with the idea that changes in idiosyncratic volatility are related to changes in the composition of the market.info:eu-repo/semantics/publishedVersio

Habit, Memory, and the Persistence of Socialist-Era Street Names in Postsocialist Bucharest, Romania

The critical study of toponymy has paid considerable attention to the renaming of urban places following revolutionary political change. Such renaming is intended to institutionalize a new political agenda through shaping the meanings in everyday practices and landscapes. Renaming, however, might not always be successful, and this article examines this issue with reference to a market in Bucharest, Romania. Originally named Piaţa Moghioroş during the socialist era to commemorate a leading Communist Party activist, the market was renamed in the postsocialist period. Yet, more than two decades on, the original name remains in widespread everyday use. Using a mixed-method approach, we seek to advance the critical toponymies literature by exploring the persistence of the socialist-era name within everyday practice. Although many authors have highlighted the issue of popular resistance to an unpopular renaming, we find little evidence of conscious resistance, and instead we explore the importance of habit within everyday practices as an explanation, drawing on an understanding of habit derived from sociocognitive psychology. This perspective proposes that habits are stable and hard to break if the broader context in which they are situated is stable. We suggest that this explanation, rather than popular contestation, has more to offer in understanding the persistence of the toponym Piaţa Moghioroş. We thus highlight the importance of considering how the “users” of place names react to the changes of such names and create their own meanings in relation to them in ways unintended by elites

Tourism and toponymy: Commodifying and Consuming Place Names

Academic geographers have a long history of studying both tourism and place names, but have rarely made linkages between the two. Within critical toponymic studies there is increasing debate about the commodification of place names, but to date the role of tourism in this process has been almost completely overlooked. In some circumstances, toponyms can become tourist sights based on their extraordinary properties, their broader associations within popular culture, or their role as metanyms for some other aspect of a place. Place names may be sights in their own right or ‘markers’ of a sight and, in some cases, the marker may be more significant than the sight to which it refers. The appropriation of place names through tourism also includes the production and consumption of a broad range of souvenirs based on reproductions or replicas of the material signage that denote place names. Place names as attractions are also associated with a range of performances by tourists, and in some cases visiting a place name can be a significant expression of fandom. In some circumstances, place names can be embraced and promoted by tourism marketing strategies and are, in turn, drawn into broader circuits of the production and consumption of tourist space

Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial

ObjectiveYKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission.MethodsNinety-nine patients with early DMARD-naive RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay.ResultsAt the baseline, plasma YKL-40 concentration was 57 +/- 37 ( mean +/- SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-alpha antagonist infliximab was added on the combination treatment.ConclusionsHigh YKL-40 levels were found to be associated with disease activity in early DMARD-naive RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission

NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) : characterisation of a novel cerebropulmonary disease

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and previously undescribed granuloma-like lesions were observed in the lungs. Hepatomegaly, steatosis and collagen accumulation were detected in the liver. A whole-exome sequencing of the two unrelated families with the affected children revealed the transmission of two heterozygous variants in the NHL repeat-containing protein 2 (NHLRC2); an amino acid substitution p.Asp148Tyr and a frameshift 2-bp deletion p.Arg201GlyfsTer6. NHLRC2 is highly conserved and expressed in multiple organs and its function is unknown. It contains a thioredoxin-like domain; however, an insulin turbidity assay on human recombinant NHLRC2 showed no thioredoxin activity. In patient-derived fibroblasts, NHLRC2 levels were low, and only p.Asp148Tyr was expressed. Therefore, the allele with the frameshift deletion is likely non-functional. Development of the Nhlrc2 null mouse strain stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos affected the integrity of cells in the midbrain region. This is the first description of a fatal, early-onset disease; we have named it FINCA disease based on the combination of pathological features that include fibrosis, neurodegeneration, and cerebral angiomatosis.Peer reviewe

Lifestyle and metabolic factors in relation to shoulder pain and rotator cuff tendinitis: A population-based study

<p>Abstract</p> <p>Background</p> <p>Shoulder pain is a common health problem. The purpose of this study was to assess the associations of lifestyle factors, metabolic factors and carotid intima-media thickness with shoulder pain and chronic (> 3 months) rotator cuff tendinitis.</p> <p>Methods</p> <p>In this cross-sectional study, the target population consisted of subjects aged 30 years or older participating in a national Finnish Health Survey during 2000-2001. Of the 7,977 eligible subjects, 6,237 (78.2%) participated in a structured interview and clinical examination. Chronic rotator cuff tendinitis was diagnosed clinically. Weight-related factors, C-reactive protein and carotid intima-media thickness were measured.</p> <p>Results</p> <p>The prevalence of shoulder joint pain during the preceding 30 days was 16% and that of chronic rotator cuff tendinitis 2.8%. Smoking, waist circumference and waist-to-hip ratio were related to an increased prevalence of shoulder pain in both genders. Metabolic syndrome, type 2 diabetes mellitus and carotid intima-media thickness were associated with shoulder pain in men, whereas high level of C-reactive protein was associated with shoulder pain in women. Increased waist circumference and type 1 diabetes mellitus were associated with chronic rotator cuff tendinitis in men.</p> <p>Conclusions</p> <p>Our findings showed associations of abdominal obesity, some other metabolic factors and carotid intima-media thickness with shoulder pain. Disturbed glucose metabolism and atherosclerosis may be underlying mechanisms, although not fully supported by the findings of this study. Prospective studies are needed to further investigate the role of lifestyle and metabolic factors in shoulder disorders.</p