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OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.
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Artritis Psoriásica , Entesopatía , Medición de Resultados Informados por el Paciente , Sistema de Registros , Humanos , Artritis Psoriásica/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Europa (Continente) , Adulto , Entesopatía/etiología , Resultado del Tratamiento , Antirreumáticos/uso terapéutico , Costo de Enfermedad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Índice de Severidad de la Enfermedad , Estudios de Cohortes , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Multifilamentary MgB2 strands (filament numbers 36 to 114) prepared by the in-situ power-in-tube (PIT) route with carbon doping contents of 0, 2, and 3.2% were wound on barrels for transport Jc and n-value measurement at 4.2 K in fields of up to 12 T. The strand and gauge lengths were 1 m and 0.5 m. Heat treatments at 675 °C and 650 °C centered around the melting point of Mg (650 °C) and both utilized the liquid-solid reaction. A pair of strands, with and without 2% C doping exhibited the Jc (B) crossover effect. Studied were the dependencies of Jc on field strength, dopant concentration, and cabling and the dependence of n-value on field strength.
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we present magnetic, mechanical and thermal modeling results for a 3 Tesla actively shielded whole body MRI (Magnetic Resonance Imaging) magnet consisting of coils with a square cross section of their windings. The magnet design was a segmented coil type optimized to minimize conductor length while hitting the standard field quality and DSV (Diameter of Spherical Volume) specifications as well as a standard, compact size 3 T system. It had an overall magnet length and conductor length which can lead to conduction cooled designs comparable to NbTi helium bath cooled 3 T MRI magnets. The design had a magnetic field homogeneity better than 10 ppm (part-per-million) within a DSV (Diameter of Spherical Volume) of 48 cm and the total magnet winding length of 1.37 m. A new class of MgB2 strand especially designed for MRI applications was considered as a possible candidate for winding such magnets. This work represents the first magnetic, mechanical and thermal design for a whole-body 3 T MgB2 short (1.37 m length) MRI magnet based on the performance parameters of existing MgB2 wire. 3 Tesla MRI magnet can operate at 20 K at 67 % of its critical current.
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Bulk samples of magnesium diboride (MgB2) doped with 0.5 wt% of the rare earth oxides (REOs) Nd2O3 and Dy2O3 (named B-ND and B-DY) prepared by standard powder processing, and wires of MgB2 doped with 0.5 wt% Dy2O3 (named W-DY) prepared by a commercial powder-in-tube processing were studied. Investigations included x-ray diffractometry, scanning- and transmission electron microscopy, magnetic measurement of superconducting transition temperature (T c), magnetic and resistive measurements of upper critical field (B c2) and irreversibility field (B irr), as well as magnetic and transport measurements of critical current densities versus applied field (J cm(B) and J c(B), respectively). It was found that although the products of REO doping did not substitute into the MgB2 lattice, REO-based inclusions resided within grains and at grain boundaries. Curves of bulk pinning force density (F p) versus reduced field (b = B/B irr) showed that flux pinning was by predominantly by grain boundaries, not point defects. At all temperatures the F p(b) of W-DY experienced enhancement by inclusion-induced grain boundary refinement but at higher temperatures F p(b) was still further increased by a Dy2O3 additive-induced increase in B irr of about 1 T at all temperatures up to 20 K (and beyond). It is noted that Dy2O3 increases B irr and that it does so, not just at 4 K, but in the higher temperature regime. This important property, shared by a number of REOs and other oxides promises to extend the applications range of MgB2 conductors.
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INTRODUCTION: Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications. AIM: The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response. METHODS: One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3-5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3-5 weeks. Sera were collected before vaccination, 18-90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA. RESULTS: Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future. CONCLUSION: Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.
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Enfermedades Autoinmunes/inmunología , Inmunogenicidad Vacunal , Inflamación/inmunología , Vacunas contra la Influenza/uso terapéutico , Enfermedades Reumáticas/inmunología , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Femenino , Estudios de Seguimiento , Humanos , Inflamación/sangre , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades Reumáticas/sangre , Adulto JovenRESUMEN
Autoantibodies against dsDNA are utilized for the diagnosis and prognosis of SLE as they are highly specific and correlate with disease activity/renal involvement. However, different detection methods are used in routine diagnostic laboratories. Farr radioimmunoassay (Farr-RIA) has been designated as the preferred method, since it provides very specific and at the same time quantitative results, enabling follow-up of level variations over time. Using intercalating fluorescent dsDNA dye would enable all the benefits of Farr-RIA without the radioactive material and organic solvents. To develop a modified fluorescent Farr method (Farr-FIA) and compare it to the classical Farr-RIA in regard to laboratory parameters, as well as clinical utility. Assays were tested on sera of 70 SLE patients, 78 other autoimmune patients, and 145 healthy blood donors. DNA for Farr-FIA was isolated from healthy donor, for Farr-RIA, 14C-labeled dsDNA from E. coli was used and mixed with sera in borate-buffered saline, followed by precipitation with saturated ammonium sulfate solution and centrifugation. The supernatant (S) was separated from the precipitate (P), and content of dsDNA was measured with PicoGreen (Invitrogen) in Farr-FIA or radioactive isotope in scintillation solution in Farr-RIA. The results were calculated as a ratio (P-S)/(P+S). Farr-FIA has a diagnostic sensitivity of 53% and diagnostic specificity of 100% (ROC AUC 0.781). Good correlation and agreement were shown between Farr-RIA and Farr-FIA. Also, there is good correlation between Farr-FIA and SLEDAI, comparable to that of Farr-RIA. Farr-FIA differs from Farr-RIA in the changed detection system yielding comparable results and thus could represent a nonradioactive replacement for Farr-RIA.
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Anticuerpos Antinucleares/sangre , Lupus Eritematoso Sistémico/sangre , Ensayo de Radioinmunoprecipitación/métodos , Adulto , Anticuerpos Antinucleares/análisis , Estudios Transversales , ADN/inmunología , Pruebas Diagnósticas de Rutina , Femenino , Humanos , Modelos Lineales , Lupus Eritematoso Sistémico/diagnóstico , MasculinoRESUMEN
OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.
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Artritis Reumatoide/tratamiento farmacológico , Sistema de Registros , Factor Reumatoide/sangre , Rituximab/uso terapéutico , Fumar/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/epidemiología , Biomarcadores/sangre , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Fumar/epidemiologíaRESUMEN
Immunoglobulin A vasculitis (IgAV) is an immune complex, small vessel vasculitis with dominant IgA deposits in vessel walls, predominantly affecting the pediatric population. However, adults frequently have more severe gastrointestinal tract (GIT) and renal involvements as compared to children. Our aim was to study serological and cellular biomarkers to support clinicians in their diagnosis and the course of IgAV in adult patients. This cross-sectional study included 62 adult IgAV patients and 53 healthy blood donors (HBDs). Demographic and clinical data, as well as routine laboratory tests, were meticulously analyzed. Serum levels of IL-1ß, IL-2, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-23, TNF-α and serum amyloid A (SAA) were measured. Percentages of neutrophils, lymphocytes, and monocytes with neutrophil expression of L-selectin and integrin αM were determined by flow cytometry. SAA (12-fold), IL-6 (3-fold), IL-8 (2-fold), and TNF-α (2-fold) were significantly elevated in sera of adult IgAV patients compared to HBDs. There was a 16% elevation in neutrophils in IgAV patients, with IgAV neutrophils showing significantly higher CD62L surface expression. IgAV patients with GIT involvement exhibited elevated numbers of leukocytes, neutrophils, and neutrophil/lymphocyte (NLR), but lower neutrophil CD11b expression, as compared to IgAV patients without GIT. IgAV patients exhibit a low-medium grade inflammatory, neutrophil-driven response. Patients with GIT can be distinguished by their elevated NLR.
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Citocinas/sangre , Vasculitis por IgA/sangre , Inmunoglobulina A/sangre , Neutrófilos/metabolismo , Adulto , Anciano , Biomarcadores/sangre , Antígeno CD11b/sangre , Estudios de Casos y Controles , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Vasculitis por IgA/inmunología , Inmunoglobulina A/inmunología , Selectina L/sangre , Masculino , Persona de Mediana EdadRESUMEN
The development of coils that can survive a quench is crucial for demonstrating the viability of MgB2-based main magnet coils used in MRI systems. Here we have studied the performance and quench properties of a large (outer diameter: 901 mm; winding pack: 44 mm thick × 50.6 mm high) conduction-cooled, react-and-wind (R&W), MgB2 superconducting coil. Minimum quench energy (MQE) values were measured at several coil operating currents (I op ), and distinguished from the minimum energy needed to generate a normal zone (MGE). During these measurements, normal zone propagation velocities (NZPV) were also determined using multiple voltage taps placed around the heater zone. The conduction cooled coil obtained a critical current (I c ) of 186 A at 15 K. As the operating currents (I op ) varied from 80 A to 175 A, MQE ranged from 152 J to 10 J, and NZPV increased from 1.3 to 5.5 cm/s. Two kinds of heater were involved in this study: (1) a localized heater ("test heater") used to initiate the quench, and (2) a larger "protection heater" used to protect the coil by distributing the normal zone after a quench was detected. The protection heater was placed on the outside surface of the coil winding. The test heater was also placed on the outside surface of the coil at a small opening made in the protection heater. As part of this work, we also developed and tested an active protection scheme for the coil. Such active protection schemes are of great interest for MgB2-based MRIs because they permit exploitation of the relatively large MQE values of MgB2 to enable the use of higher J e values which in turn lead to competitive MgB2 MRI designs. Finally, the ability to use a quench detection voltage to fire a protection heater as part of an active protection scheme was also demonstrated.
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BACKGROUND: RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. AIM: To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). METHODS: HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. RESULTS: SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. CONCLUSION: We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.
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Vasos Coronarios/citología , Células Endoteliales/metabolismo , Proteína Amiloide A Sérica/farmacología , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Giant cell arteritis (GCA) is a primary systemic vasculitis present in subjects older than 50years with involvement of large- and medium-sized arteries. Early diagnosis for GCA is essential to prevent serious complications, such as permanent vision loss and/or cerebrovascular events. Elevated inflammatory cytokines, with acute phase and other proteins dominate large- and medium-sized arteries leading to stenosis or occlusion of arterial lumen. To date, there are no reliable serological markers for monitoring GCA. The review aims to provide concise overview of published GCA studies in order to: a) identify significantly changed serological biomarkers in GCA and compare the influences of techniques for marker evaluation and b) investigate most promising markers in GCA using analyte frequency and meta-analysis.
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Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Arteritis de Células Gigantes/diagnóstico , HumanosRESUMEN
Standard in-situ type MgB2 strands manufactured by Hyper Tech Inc have 19 - 36 subelements, a monel outer sheath, and a Cu interfilamentary matrix. Typical transport Jc s of the strands are 2×105 A/cm2 with n-values of 20 - 30 at 4.2 K and 5 T. This work introduces two new MgB2 conductor designs. First, a new class of MgB2 strand is designed for magnetic resonance imaging applications. This type has a higher Cu content designed to enhance protection of a magnet wound with it, and a larger diameter to increase the critical current. Second, a new class of low AC loss MgB2 strand with high filament count and a high resistance matrix is discussed. Transport properties at 4.2 K and fields up to 10 T are reported. Optical techniques are used to study the macro- and micro-structures of these MgB2 strands.
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Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results In the initial study ( n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed ( k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study ( n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed ( k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Fosfatidilserinas/inmunología , Complicaciones del Embarazo/diagnóstico , Trombosis/diagnóstico , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/sangre , Estudios Transversales , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/sangre , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
We describe a novel approach to investigate and evaluate combined effect of a large number of clinical and pharmacogenetic factors on treatment outcome. We have used this approach to investigate predictors of methotrexate (MTX)-induced adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in MTX transporters, folate and adenosine pathways. The effect of clinical and pharmacogenetic factors was assessed with penalized regression in the cause-specific Cox proportional hazards model. The predictive capacity was evaluated with the area under time-dependent receiver operating characteristic curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were associated with discontinuation because of AEs in clinical-pharmacogenetic model. Cross-validation showed that both clinical-pharmacogenetic model and nongenetic model had worthless predictive ability for MTX discontinuation because of AEs. These models could be further improved, either with additional polymorphisms or with epigenetic predictors.
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Antirreumáticos/efectos adversos , Antirreumáticos/farmacocinética , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/efectos adversos , Metotrexato/farmacocinética , Polimorfismo Genético , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/genética , Femenino , Genotipo , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Transporte de Nucleósidos/genética , Pruebas de Farmacogenómica , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Proteína Portadora de Folato Reducido/genética , Timidilato Sintasa/genética , Resultado del TratamientoRESUMEN
This study is a contribution to the development of technology for an MgB2-based, cryogen-free, superconducting magnet for an MRI system. Specifically, we aim to demonstrate that a react and wind coil can be made using high performance in-situ route MgB2 conductor, and that the conductor could be operated in conduction mode with low levels of temperature gradient. In this work, an MgB2 conductor was used for the winding of a sub-size, MRI-like coil segment. The MgB2 coil was wound on a 457 mm ID 101 OFE copper former using a react-and-wind approach. The total length of conductor used was 330 m. The coil was epoxy impregnated and then instrumented for low temperature testing. After the initial cool down (conduction cooling) the coil Ic was measured as a function of temperature (15-30 K), and an Ic of 200 A at 15 K was measured.
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OBJECTIVES: The mechanism by which methotrexate (MTX) improves glucose homeostasis in patients with rheumatoid (RA) and psoriatic arthritis (PsA) remains undetermined. Animal studies indicate a role for intracellular accumulation of 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranosyl 5'-monophosphate (ZMP) but this has not been directly demonstrated in humans. We explored whether accumulation of ZMP is associated with improvements in glucose homeostasis during MTX therapy. METHOD: MTX-naïve, non-diabetic RA (n = 16) and PsA (n = 10) patients received uninterrupted MTX treatment for 6 months. To evaluate whether ZMP accumulated during MTX therapy, we measured the concentration of ZMP in erythrocytes and the concentration of its dephosphorylated derivative 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) in urine using liquid chromatography mass spectrometry (LC-MS/MS). To assess glucose homeostasis, we determined the concentration of glycated haemoglobin (HbA1c) and homeostasis model assessment of insulin resistance [HOMA-IR: fasting glucose (mmol/L) × fasting insulin (µU/mL)/22.5]. RESULTS: Erythrocyte ZMP and urinary AICAR concentrations did not increase during 6 months of MTX therapy. HbA1c concentration was reduced from 5.80 ± 0.29% at baseline to 5.51 ± 0.32% at 6 months (p < 0.001), while HOMA-IR remained unaltered. Reduction in HbA1c concentration was not associated with increased ZMP or AICAR concentrations. CONCLUSIONS: MTX therapy probably does not produce a chronic increase in erythrocyte ZMP or urinary AICAR concentrations. Collectively, our data do not support the hypothesis that MTX improves glucose homeostasis through chronic accumulation of ZMP.
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Aminoimidazol Carboxamida/análogos & derivados , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Glucemia/metabolismo , Hemoglobina Glucada/metabolismo , Insulina/metabolismo , Metotrexato/uso terapéutico , Ribonucleótidos/metabolismo , Adulto , Anciano , Aminoimidazol Carboxamida/metabolismo , Artritis Psoriásica/metabolismo , Artritis Reumatoide/metabolismo , Cromatografía Liquida , Eritrocitos/metabolismo , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Espectrometría de Masas en TándemRESUMEN
The influences of strand twisting and bending (applied at room temperature) on the critical current densities, Jc , and n-values of MgB2 multifilamentary strands were evaluated at 4.2 K as function of applied field strength, B. Three types of MgB2 strand were evaluated: (i) advanced internal magnesium infiltration (AIMI)-processed strands with 18 filaments (AIMI-18), (ii) powder-in-tube (PIT) strands processed using a continuous tube forming and filling (CTFF) technique with 36 filaments (PIT-36) and (iii) CTFF processed PIT strands with 54 filaments (PIT-54). Transport measurements of Jc(B) and n-value at 4.2 K in fields of up to 10 T were made on: (i) PIT-54 after it was twisted (at room temperature) to twist pitch values, Lp , of 10-100 mm. Transport measurements of Jc(B) and n-value were performed at 4.2 K; (ii) PIT-36 and AIMI-18 after applying bending strains up to 0.6% at room temperature. PIT-54 twisted to pitches of 100 mm down to 10 mm exhibited no degradation in Jc(B) and only small changes in n-value. Both the Jc(B) and n-value of PIT-36 were seen to be tolerant to bending strain of up to 0.4%. On the other hand, AIMI-18 showed ±10% changes in Jc(B) and significant scatter in n-value over the bending strain range of 0-0.6%.
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BACKGROUND: IgA vasculitis (IgAV) is assumed to be uncommon in adults. OBJECTIVES: To determine the incidence rate of histologically proven IgAV in the adult Slovenian population. METHODS: A retrospective chart review of adult patients diagnosed with IgAV was performed at the departments of rheumatology, nephrology, infectious diseases and dermatovenereology at an integrated secondary/tertiary university teaching hospital. In order to avoid missing miscoded cases, the Institute of Pathology, University of Ljubljana, Slovenia, provided a list of all patients with an IgAV-compatible histological pattern on biopsy. The annual incidence rate of histologically proven IgAV was calculated. RESULTS: Eighty-one new cases of IgAV were identified from June 2010 to June 2013. The estimated annual incidence rate of IgAV was 5·1 per 100,000 adults [95% confidence interval (CI) 3·4-7·4]; in men it was 6·1 per 100,000 (95% CI 3·9-10·6) and in women it was 3·7 per 100,000 (95% CI 1·8-6·8). CONCLUSIONS: Although we only included histologically proven cases of IgAV, the annual incidence rate of 5·1 per 100,000 adults is 3-6-times higher than previously reported.
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Inmunoglobulina A , Vasculitis/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Distribución por Sexo , Eslovenia/epidemiología , Adulto JovenRESUMEN
Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.
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OBJECTIVE: To test the feasibility of dynamic contrast enhanced (DCEI) and diffusion weighted (DWI) magnetic resonance imaging (MRI) for quantifying synovitis of the cranio-cervical (C-C) region in patients with early rheumatoid arthritis (RA) and neck pain at the beginning and at a six month follow up. METHODS: 27 patients with duration of RA of less than 24 months and neck pain were studied with standard qualitative MRI evaluation and two quantitative MRI methods (DCEI and DWI) at the level of atlantoaxial joints. Rate of early enhancement (REE), enhancement gradient (Genh) and apparent diffusion coefficient (ADC) were extracted from DCEI and DWI data. MRI was coupled with clinical assessment and radiographic imaging. RESULTS: Using standard qualitative MRI evaluation, unequivocal active synovitis (grade 2 or 3 contrast enhancement) was proved in 16 (59%) patients at baseline and 14 (54%) at follow up. DCEI and DWI measurements confirmed active synovitis in 25 (93%) patients at baseline and 24 (92%) at follow up. Average REE, Genh and ADC values decreased during follow up, however the difference was not statistically significant (p>0.05). Both qualitative and quantitative MRI methods confirmed active inflammatory disease in the C-C region following therapy although all clinical criteria showed signs of improvement of the peripheral disease. CONCLUSIONS: The study proved the feasibility of DCEI and DWI MRI for quantifying synovitis of the C-C region in patients with early RA and neck pain. Both techniques can be used as additional method for evaluation of synovitis of the C-C region in RA.