The LHCb Vertex Locator (VELO) is used to reconstruct beam–gas interaction vertices which allows one to obtain precise profiles of the LHC beams. In LHCb, this information is combined with the ...profile of the reconstructed beam–beam collisions and with the LHC beam currents to perform precise measurements of the luminosity. This beam–gas imaging (BGI) method also allows one to study the transverse beam shapes, beam positions and angles in real time. Therefore, a demonstrator beam–gas vertex detector (BGV) based on scintillating fibre modules has been built and installed in LHC Ring 2 at point 4.
The following review summarizes the evidence on reactive arthritis (ReA), focussing on the latest relevant work on epidemiology, diagnosis, pathogenesis, and treatment. ReA is a joint inflammation ...that develops after a primary, extra-articular infection; the infection often involves the urogenital or gastrointestinal system, and less frequently the respiratory tract. The microbial agent causing the primary infection and triggering the arthritis cannot be cultured from the synovial compartment by standard methods; however, bacterial antigens or nucleic acids originating from Chlamydia trachomatis and other microbes can be detected within joint material. ReA occurs worldwide with a prevalence of 40/100,000 and an incidence of 5/100,000. The arthritis develops within days or weeks after the primary infection and usually affects the lower extremities. A dactylitis of the toes is highly typical, while axial or extra-articular manifestations are less common. The disease subsides in many cases within weeks or months, however relapses can occur and chronic forms are described in 30 % of patients.Antibiotic treatment is recommended for the active primary infection. Treatment of ReA focuses on alleviation of signs and symptoms. Severe and chronic forms require the use of immunomodulatory agents.
In order to reduce the prognostically relevant time interval between the initial manifestation of a rheumatic and musculoskeletal disease and diagnosis as well as the consecutive initiation of an ...appropriate treatment, several rheumatological centers in Germany have improved the access to initial rheumatologic evaluation by establishing early recognition/screening clinics at their respective sites. Corresponding models located at Altoetting·Burghausen, Bad Pyrmont, Berlin Buch, Duesseldorf, Heidelberg, Herne, Mannheim as well as supraregional/multicenter initiatives Rheuma Rapid, RhePort and Rheuma-VOR are presented in this overview along with the respective characteristics, potential advantages and disadvantages, but also first evaluation results of several models. The aim of this publication is to promote early detection of rheumatic and musculoskeletal diseases as one of the most important challenges in current rheumatology by encouraging further rheumatologic centers and practices to launch their own early recognition/screening consultation model on the basis of aspects presented herein.
Zusammenfassung
Die vorliegende Übersicht fasst den aktuellen Wissenstand über die reaktive Arthritis (ReA) zusammen; auf neuere und relevante Publikationen zu Epidemiologie, Diagnostik, Pathogenese ...und Therapie wird ausführlich eingegangen. Die ReA ist eine Gelenkentzündung, die sich als Folge einer vorausgehenden extraartikulären bakteriellen Infektion entwickelt. Diese wird als Primärinfektion bezeichnet und betrifft häufig das urogenitale oder gastrointestinale, seltener auch das respiratorische System. Die ReA tritt weltweit auf, die Prävalenz wird mit 40/100.000 und die Inzidenz mit 5/100.000 angegeben.
Der Erreger der Primärinfektion und Auslöser der Arthritis lässt sich aus Gelenkmaterial nicht kultivieren, häufig beschränkt sich der Erregernachweis auf indirekte Verfahren wie z. B. die Serologie. Ansonsten sollte der direkte Nachweis – überwiegend mittels molekularbiologischer Verfahren – am Ort der Primärinfektion oder bei
Chlamydia trachomatis
-assoziierter ReA auch im Gelenk angestrebt werden.
Typisch für das klinische Bild ist eine asymmetrische Arthritis der unteren Extremität oder eine Daktylitis der Zehen, die Tage bis Wochen nach der Primärinfektion akut auftritt; eine axiale Beteiligung oder extraartikuläre Manifestationen sind seltener. Im Verlauf von Wochen bis Monaten klingt die ReA in vielen Fällen wieder ab. Rezidive sind möglich, in bis zu 30 % kommt es zu chronischen Verläufen. Die medikamentöse Behandlung der ReA zielt auf eine Linderung der Symptome und den Rückgang der Entzündung ab, für chronische Formen sind immunmodulierende Basistherapien indiziert. Eine antibiotische Behandlung wird nur für die aktive Primärinfektion empfohlen.
Research on the molecular biology of Chlamydia is hampered by its obligate intracellular life form, its biphasic developmental cycle, the lack of genetic transformation systems, and the lack of ...suitable animal models for reactive arthritis. ...only recently has an insight into the chlamydial genome become available. 12 The genome of the C trachomatis serovar D was first published in 1998, identifying 894 likely protein coding genes among the 1 042 519 base pairs. 13 More recently, an analysis of the chlamydial proteome has led to the identification of 328 proteins. 14 However, the function of the majority of genes and proteins has not been elucidated so far. During the following days, other mechanisms seem to become prominent. 23 These TLR independent interactions can best be observed in epithelial cells.\n Apart from the attempt to define the genes and the molecular mechanisms of persistent C trachomatis infection, this report provides further important information: in contrast with M tuberculosis, probably because of its much smaller genome, C trachomatis does not dispose of a set of genes solely inducing and maintaining a persistent infection state. ...it seems obvious that C trachomatis merely adapts and adjusts its level of gene expression in order to elicit this particular state of infection.
The beam-gas vertex (BGV) detector is an innovative instrument measuring noninvasively the transverse beam size in the Large Hadron Collider (LHC) using reconstructed tracks from beam-gas ...interactions. The BGV detector was installed in 2016 as part of the R&D for the High-Luminosity LHC project. It allows beam size measurements throughout the LHC acceleration cycle with high-intensity physics beams. A precision better than 2% with an integration time of less than 30 s is obtained on the average beam size measured, while the transverse size of individual proton bunches is measured with a resolution of 5% within 5 min. Particles emerging from beam-gas interactions in a specially developed gas volume along the beam direction are recorded by two tracking stations made of scintillating fibers. A scintillator trigger system selects, on-line, events with tracks originating from the interaction region. All the detector elements are located outside the beam vacuum pipe to simplify the design and minimize interference with the accelerated particle beam. The beam size measurement results presented here are based on the correlation between tracks originating from the same beam-gas interaction vertex.
Autoimmune rheumatic diseases are generally considered as a multifactorial aetiology, mainly genetic susceptibility combined with environmental triggers of which bacteria are considered one of the ...most prominent. Among the rheumatic diseases where bacterial agents are more clearly involved as triggers are: reactive arthritis (ReA), rheumatic fever (RF) and Lyme disease. The role of bacterial infections in inducing other seronegative spondyloarthritis and antiphospholipid antibody syndrome has been hypothesized but is still not proven. The classic form of ReA is associated with the presence of HLA-B27 and is triggered by the urethritis or enteritis causing pathogens Chlamydia trachomatis and the enterobacteria Salmonella, Shigella, and Yersinia, respectively. But several other pathogens such as Brucella, Leptospira, Mycobacteria, Neisseria, Staphylococcus and Streptococcus have also been reported to cause ReA. RF is due to an autoimmune reaction triggered by an untreated throat infection by Streptococcus pyogenes in susceptible individuals. Carditis is the most serious manifestation of RF and HLA-DR7 is predominantly observed in the development of valvular lesions. Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Knowledge is limited about how this spirochete interacts with human tissues and cells. Some data report that Borrelia burgdorferi can manipulate resident cells towards a pro- but also anti-inflammatory reaction and persist over a long period of time inside the human body or even inside human cells.
Objective: To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with ...spondyloarthritis (SpA). Material and Methods: Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor α antibody, infliximab. Results: mRNA transcripts of all NTs and receptors were expressed in the inflamed synovium. At the protein level, brain derived neurotrophic factor and NT-3 were significantly higher in the SF of patients with SpA than in those with OA. In contrast, ELISA of serum samples showed that the highest member in SpA was NT-4. Immunohistochemistry demonstrated that the NT receptors trkA and NGFRp75 were highly expressed in the inflamed synovium of patients with SpA, correlating with vascularity and lymphoid aggregates, respectively. Additionally, immunoreactivity of both receptors was significantly decreased after infliximab treatment. Conclusions: NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes.
To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, ...and to identify which cytokines/chemokines are being expressed and which cell fractions are involved.
Gene expression profiles were generated by microarray screening of SFMC of 5 patients with SpA, 5 patients with rheumatoid arthritis (RA), and peripheral blood mononuclear cells (PBMC) of 6 controls. Results were validated by reverse transcription polymerase chain reaction using samples from a larger panel of subjects.
The repertoires of proinflammatory cytokines/chemokines expressed by SpA and RA SFMC were very similar: monocyte chemotractant protein 1 (MCP-1), interleukin 8 (IL-8), IL-1beta, endothelial-monocyte activating polypeptide II, interferon-gamma, and tumor necrosis factor-alpha. MCP-1 was highly expressed in SpA SFMC. There was enhanced expression of immunoglobulin heavy chain binding protein (BiP) in SpA, which is compatible with the UPR hypothesis. BiP was most highly expressed in the adherent fraction of SpA SFMC.
Previous data postulating UPR in SpA are based on in vitro experiments with transfected cell lines. Our patient derived data suggest that it also occurs in vivo in the macrophages of SpA joints.
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