1,077 research outputs found

    The role of the forkhead transcription factor Foxo3 in erythropoiesis

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    The role of the forkhead transcription factor Foxo3 in erythropoiesis

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    Cumulative Corticosteroid Sparing Effect of Anti-Interleukin-5/5Ra In Eosinophilic Asthma

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    BACKGROUND: Anti-interleukin (IL)-5/IL-5 receptor α (IL-5Ra) therapy has been shown to reduce maintenance oral corticosteroid (OCS) dose in severe eosinophilic asthma. However, the effect on cumulative OCS exposure is currently unknown. Neither is it known how prior OCS exposure affects response to anti-IL-5/5Ra treatment. We aimed primarily to compare the cumulative OCS exposure over a 2-year period before and after anti-IL-5/5Ra initiation, and secondarily to investigate whether duration and cumulative OCS exposure prior to anti-IL-5/5Ra influence the ability to discontinue OCS within 2 years of anti-IL-5/5Ra therapy. METHODS: This real-world nationwide observational registry-based study evaluated all dispensed OCS from 389 adults with severe eosinophilic asthma included in the Dutch Severe Asthma Registry (RAPSODI) 2 years before and 2 years after initiating anti-IL-5/5Ra. The Wilcoxon signed-rank test and multivariable regression analyses were used. RESULTS: Median (interquartile range) cumulative OCS exposure in the 2 years before and after anti-IL-5/5Ra initiation decreased from 2.715 (1.150–5.539) to 1.050 (0.300–3.640) g (p<0.001). 52% of patients were able to discontinue OCS within 2 years after anti-IL-5/5Ra therapy, which was independently predicted by lower and shorter prior OCS exposure. CONCLUSIONS: This real-world study showed that anti-IL-5/5Ra therapy leads to a significant reduction in cumulative OCS exposure over a 2-year period. Patients with lower and shorter OCS exposure were more likely to completely eliminate OCS. Since cumulative exposure increased progressively prior to anti-IL-5/5Ra initiation, our data suggest that early intervention leads to a better long-term prognosis in patients with severe eosinophilic asthma

    Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

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    In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity

    The Impact of a SIG on Assessment Literacy

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    A major aim of professional associations is to provide opportunities for professionals to interact with others, share ideas and develop in their chosen profession. Professional associations exist to provide specialized networking and development opportunities to a specific profession, group of individuals or field of study. To promote and support specialized research and communication, smaller subgroups within an association are often chartered or developed. These subgroups are typically known as Special Interest Groups. According to Jacob et al. (2013), association members join SIGs because they want to go deeper into a specialized content area and they enjoy networking with others who ‘speak the same language.’ The TESOL Arabia Testing, Assessment and Evaluation SIG (TAE SIG) has focused their professional development activities on an important trend in the field, that of language assessment literacy (LAL). Language assessment literacy has been a critical topic in English language teaching since the late 1990s. Unfortunately, this is mainly due to the fact that so many English language teachers are not assessment literate. In other words, many English language teachers lack the knowledge and skills to write effective language tests, evaluate the effectiveness of their tests, and use their test results in meaningful ways. The purpose of this chapter is to critically examine the status of LAL in the Middle East and North Africa (MENA) region and report on activities that the TAE SIG has implemented to increase LAL
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