Spondylarthropathies in children--are they different from those in adults?

Juvenile spondylarthropathies (JSpAs) comprise a group of rheumatic diseases distinct from other categories of juvenile arthritis. Several classification systems have been applied, and some are specific for children, such as the seronegative enthesopathy and arthropathy (SEA) syndrome and the enthesitis-related arthritis, diagnostic forms in the International League of Associations for Rheumatism (ILAR) classification. JSpA seems more frequent than was previously believed, but actual epidemiological data show important variations between studies. Compared to adult patients, children with JSpA present with peripheral arthritis and enthesitis early in disease but sacroiliac and spine joints involvement many years later. A multidisciplinary team in a paediatric environment should be responsible for the management of children with spondylarthropathies to ensure the best care for these children with their chronic disease and risk of long-term disability. Recent advances in the treatment of rheumatic diseases with biological agents show promising results in children with JSpA. Further research needs to be conducted to increase our knowledge of the long-term outcome of these patients, to improve management, and to prevent long-term consequences of the disease.

Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing.

Double-strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single-strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52-mediated annealing.

Le football, ses dieux et ses démons. Menaces et atouts d'un jeu déréglé

Cet essai sur le football est un livre foisonnant sur le sport le plus populaire de l'humanité. Ethicien, théologien et fervent supporter, Denis Müller est un passionné du foot dont il suit les moindres péripéties locales ou internationales depuis plus de 50 ans. Considéré comme l'un des deux ou trois meilleurs intellectuels réfléchissant à ce sport dans l'aire francophone, il intervient souvent dans les médias pour analyser avec recul et empathie un phénomène qui dépasse parfois l'entendement. Régulièrement sollicité pour écrire un ouvrage sur le foot, Denis Müller relève enfin ce défi et de la plus belle manière. Mêlant souvenirs personnels, considérations éthiques, sociologiques ou théologiques, étudiant l'évolution du foot pour en identifier les perversions et les promesses, Denis Müller aborde tour à tour son histoire, ses règles, le fanatisme, le rapport des femmes à ce sport, l'arbitrage, le dopage ou encore les affaires. Mais ce livre est aussi un hymne, un éloge enthousiaste et lucide à une activité significative de notre modernité collective.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Plantar pressures in the tennis serve.

In-shoe loading patterns were examined in each foot (back and front) separately during two types of tennis serve [first (or flat) and second (or twist) serve] and two service stance styles [foot-up (back foot is moved forward next to front foot for push-off) and foot-back (feet remain at the same relative level)]. Ten competitive tennis players completed five trials for each type of serve and service stance style in random order. Plantar pressure distribution was recorded using Pedar insoles divided into nine areas for analysis. Mean and peak pressures (+15.2%, P < 0.01 and +12.8%, P < 0.05) as well as maximal forces (+20.2%, P < 0.01) were higher under the lateral forefoot of the front foot in first than in second serves, while mean forces were higher (+17.2%, P < 0.05) under the lesser toes. Relative load was higher on the lateral forefoot (+20.4%, P < 0.05) but lower (-32.5%, P < 0.05) on the medial heel of the front foot with foot-up compared with foot-back stance. Using a foot-up stance, loading of the back foot was higher (+31.8%, P < 0.01) under the lateral mid-foot but lower (-29.9%, P < 0.01) under the medial forefoot. The type of serve and the stance style adopted have a significant effect on foot loading. Such findings might help improve mechanical efficiency of the serve.

Octacalcium Phosphate (OCP) Crystals Induce Synovial Inflammation and Cartilage

Introduction: The presence of intra-articular basic calcium phosphate (BCP) crystals, including OCP, carbonated-apatite, hydroxyapatite and tricalcium phosphate crystals, is associated with severe osteoarthritis and destructive arthropathies such as Milwaukee shoulder. Although BCP crystals displayed, in vitro, mitogenic, anabolic and catabolic responses, their intra-articular effect was never assessed.Objective: To determine the effects of OCP crystals in joints in vivo.Methods: OCP crystals (200 ug in 20 ml PBS) were injected into the right knee joint (the contra-lateral knee joint injected with 20 ul of PBS serving as a control) of wild-type mice treated or not by the IL1R antagonist Anakinra or mice deficient for the inflammasome proteins ASC and NALP3. 4 days and 17 days after crystal injection, mice were sacrificed and knee joints dissected. Histological scoring for synovial inflammation and characterisation of macrophages, neutrophils and T cells were performed. Technetium (Tc) uptake was measured at 6h, 1 and 4 days after OCP injection. Cartilage degradation was evaluated by Safranin O staining and VDIPEN immunohistochemistry. Intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining.Results: The intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining performed on non-decalcified samples embedded in methyl-metacrylate. Injection of OCP crystals into knee joints led at day 4 to an inflammatory response with intense macrophage staining and also some neutrophil recruitment in the synovial membrane. This synovitis was not accompanied by increased Tc uptake into the knee joint, Tc uptake being similar in OCP crystal injected knee or control knee at all time points investigated (6h, 1 day, 4 days). The histological modifications persisted over 17 days, with an additional fibrosis evidenced at this later time-point. The OCP crystal-induced synovitis was totally IL-1a and IL-1 independent as shown by the absence of inhibitory effects of anakinra injected into wild-type mice. Accordingly, OCP crystal-induced synovitis was similar in ASC-/- and NALP3-/- mice as no alterations of inflammation were demonstrated between these mice groups. Concerning cartilage matrix degradation, OCP crystals induced a strong breakdown of proteoglycans 4 and 17 days after injection, as measured by loss of red staining from Safranin O-stained sections of cartilage surfaces. In addition, we also measured advanced cartilage matrix destruction mediated by MMPs, as evidenced by VDIPEN staining of cartilage. OCP-mediated cartilage degradation was similar in all experimental conditions tested (WT+Anakinra, or ASC or NALP3 deficient mice).Conclusion: These data indicate in vivo that the intra-articular presence of OCP crystals is associated with cartilage destruction along with synovial inflammation. This is an interesting and new model of destructive arthropathy related to BCP crystals which will allow to assess new therapies in this disease.

Role of defensins and cathelicidin LL37 in auto-immune and auto-inflammatory diseases.

Defensins and cathelicidins are anti-microbial peptides (AMPs) that act as natural antibiotics and are part of the innate immune defence in many species. We consider human defensins and LL37, the only human member of the cathelicidin family. In particular, we refer to the human alpha-defensins called human neutrophil peptides (HNP1 through 4), which are produced by neutrophils, HD5 and HD6, mainly expressed in Paneth cells of intestine, the human beta-defensins HBD1, HBD2 and HBD3, synthesized by epithelial cells and LL37, which is located in granulocytes, but is also produced by epithelial cells of the skin, lungs, and gut. In the last years, the study of AMPs activity and regulation has allowed to understand the important role of these peptides not only in the innate defence mechanisms against bacteria, viruses, fungi, but also in the regulation of immune cell activation and migration. Complementary studies have disclosed a role for AMPs in modulating many physiological processes that involve non-immune cells, such as activation of wound healing, angiogenesis, cartilage remodeling. Due to the pleiotropic tasks of these peptides, many of them are now being discovered to contribute to immune pathology of chronic diseases that affect skin, gut, joints; this is supported by many examples of immune-mediated pathologies in which their expression is disregulated. In this article we review the current literature that suggests a role for human defensins and LL37 in pathogenic mechanisms of several chronic diseases that are considered of auto-immune or auto-inflammatory origin.

Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy.

Elevated plasma urate levels are associated with metabolic, cardiovascular, and renal diseases. Urate may also form crystals, which can be deposited in joints causing gout and in kidney tubules inducing nephrolithiasis. In mice, plasma urate levels are controlled by hepatic breakdown, as well as, by incompletely understood renal processes of reabsorption and secretion. Here, we investigated the role of the recently identified urate transporter, Glut9, in the physiological control of urate homeostasis using mice with systemic or liver-specific inactivation of the Glut9 gene. We show that Glut9 is expressed in the basolateral membrane of hepatocytes and in both apical and basolateral membranes of the distal nephron. Mice with systemic knockout of Glut9 display moderate hyperuricemia, massive hyperuricosuria, and an early-onset nephropathy, characterized by obstructive lithiasis, tubulointerstitial inflammation, and progressive inflammatory fibrosis of the cortex, as well as, mild renal insufficiency. In contrast, liver-specific inactivation of the Glut9 gene in adult mice leads to severe hyperuricemia and hyperuricosuria, in the absence of urate nephropathy or any structural abnormality of the kidney. Together, our data show that Glut9 plays a major role in urate homeostasis by its dual role in urate handling in the kidney and uptake in the liver.

Musculoskeletal Conditions Briefing

Musculoskeletal conditions (MSCs) are a group of diseases that affect the body’s bones, joints, muscles and the tissues that connect them. Common MSCs include back pain, rheumatoid arthritis, osteoarthritis, osteoporosis, and spinal disorders. MSCs are the most common cause of severe long term pain and physical disability in developed countries. They significantly affect the psychosocial wellbeing of individuals as well as their families and carers. They are responsible for substantial costs to the health and social care system and the economy. They are a leading cause of absence from work and lost productivity at work. MSCs comprise a diverse group of conditions. Some have a specific medical diagnosis (eg rheumatoid arthritis) but others have no clear medical diagnosis (eg back pain). Risk factors for the development and progression of MSCs include age, sex, family history, obesity, physical inactivity, injury and biomechanical occupational health issues.

Musculoskeletal Conditions Briefing: Technical Documentation

Musculoskeletal conditions (MSCs) are a group of diseases that affect the body’s bones, joints, muscles and the tissues that connect them. Common MSCs include back pain, rheumatoid arthritis, osteoarthritis, osteoporosis, and spinal disorders. MSCs are the most common cause of severe long term pain and physical disability in developed countries. They significantly affect the psychosocial wellbeing of individuals as well as their families and carers. They are responsible for substantial costs to the health and social care system and the economy. They are a leading cause of absence from work and lost productivity at work. MSCs comprise a diverse group of conditions. Some have a specific medical diagnosis (eg rheumatoid arthritis) but others have no clear medical diagnosis (eg back pain). Risk factors for the development and progression of MSCs include age, sex, family history, obesity, physical inactivity, injury and biomechanical occupational health issues. This document details the methods used to calculate the estimates and forecasts.

Prevalence of chronic conditions – Musculoskeletal Conditions

IPH has estimated and forecast the number of adults with MSCs for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007 . The data describe the number of people who report that they have experienced doctor-diagnosed MSC in the previous 12 months:     Lower back pain or any other chronic back condition     Rheumatoid arthritis (inflammation of the joints)     Osteoarthritis (arthrosis, joint degradation) Data are  available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data are based on the Health and Social Wellbeing Survey 2005/06 and Understanding Society 2009. The data describe the number of adults who:     Have ever consulted a doctor about back pain     Are currently receiving treatment for musculoskeletal problems (such as arthritis, rheumatism)     Have ever been told by a doctor or other health professional that they had have arthritis? Data are available by age and sex for each Local Government District in Northern Ireland. There are significant differences between the definitions used in RoI and NI and North-South comparisons are not valid. The RoI measures relate to specific MSCs in the previous 12 months that had been diagnosed by a doctor. The NI measures relate to doctor-consultations at any time in the past, doctor-diagnosis at any time in the past and current treatment. The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Ambulatory measurement of ankle kinetics for clinical applications.

This study aimed to design and validate the measurement of ankle kinetics (force, moment, and power) during consecutive gait cycles and in the field using an ambulatory system. An ambulatory system consisting of plantar pressure insole and inertial sensors (3D gyroscopes and 3D accelerometers) on foot and shank was used. To test this system, 12 patients and 10 healthy elderly subjects wore shoes embedding this system and walked many times across a gait lab including a force-plate surrounded by seven cameras considered as the reference system. Then, the participants walked two 50-meter trials where only the ambulatory system was used. Ankle force components and sagittal moment of ankle measured by ambulatory system showed correlation coefficient (R) and normalized RMS error (NRMSE) of more than 0.94 and less than 13% in comparison with the references system for both patients and healthy subjects. Transverse moment of ankle and ankle power showed R>0.85 and NRMSE<23%. These parameters also showed high repeatability (CMC>0.7). In contrast, the ankle coronal moment of ankle demonstrated high error and lower repeatability. Except for ankle coronal moment, the kinetic features obtained by the ambulatory system could distinguish the patients with ankle osteoarthritis from healthy subjects when measured in 50-meter trials. The proposed ambulatory system can be easily accessible in most clinics and could assess main ankle kinetics quantities with acceptable error and repeatability for clinical evaluations. This system is therefore suggested for field measurement in clinical applications.

Apoptosis as a target for gene therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages and plasma cells, all of which manifest signs of activation. All these cells proliferate abnormally, invade bone and cartilage, produce an elevated amount of pro-inflammatory cytokines, metalloproteinases and trigger osteoclast formation and activation. Some of the pathophysiological consequences of the disease may be explained by the inadequate apoptosis, which may promote the survival of autoreactive T cells, macrophages or synovial fibroblasts. Although RA does not result from single genetic mutations, elucidation of the molecular mechanisms implicated in joint destruction has revealed novel targets for gene therapy. Gene transfer strategies include inhibition of pro-inflammatory cytokines, blockade of cartilage-degrading metalloproteinases, inhibition of synovial cell activation and manipulation of the Th1-Th2 cytokine balance. Recent findings have iluminated the idea that induction of apoptosis in the rheumatoid joint can be also used to gain therapeutic advantage in the disease. In the present review we will discuss different strategies used for gene transfer in RA and chronic inflammation. Particularly, we will highlight the importance of programmed cell death as a novel target for gene therapy using endogenous biological mediators, such as galectin-1, a beta-galactoside-binding protein that induces apoptosis of activated T cells and immature thymocytes.

Feasibility Study On A Helicopter Emergency Medical Service (HEMS) For The Island Of Ireland

A feasibility study on the costs and benefits associated with the introduction of dedicated Helicopter Emergency Medical Service (HEMS) was commissioned by the Department of Health and Children, Dublin and the Department of Health, Social Services and Public Safety, Belfast. The study was commissioned on foot of advice by the Cross Border Working Group on Pre-Hospital Care Working Group, one of the Groups established under the “Good Friday Agreement”.