Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: a) TCZ route (SC vs. IV); b) GCA duration (≤6 vs. >6 months); c) serious infections (with or without); d) ≤15 vs. >15 mg/day at TCZ onset. Results: 134 patients; mean age, 73.0±8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p<0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1 st hour (p<0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p<0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. Conclusion: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials.
Imbalanced nutrient management has caused soil phosphorus (P) to become an environmental rather an agronomic problem in more economically developed countries. This subject has been the topic of numerous journal special issues, conferences, and reviews but we consider yet another review of this subject is necessary with the main target of providing a point of view on nonpoint transfer from soils and control strategies for an improved environmental management of P. This review considers the causes of the excessive P transfer from soil to surface water in Europe and the scientific knowledge necessary to develop control strategies. There has been an increasing trend towards the P-research integration across Europe. The identification of critical source areas (CSA) for P loss at catchment level and the selection of best management practices (BMP) adapted at individual CSA are recognized by the scientific community as a main goal to reduce P losses. However, the adaptation of the CSA conceptual framework at European scale is not undemanding, not only due to the administrative differences between countries, but also to the heterogeneity of the landscape (area, as perceived by people, whose character is the result of the action and interaction of natural and/or human factors; CoE [2000]) in Europe (larger than in N America), the wide range of land use and management, and also to differences in the basic scientific information available in each country necessary to perform it. In the EU, policy context and environmental concerns about the effect of nutrient excesses in water were reflected in EU directives (early 1990s) mainly focussed on the reduction of nitrogen loads. Nevertheless, a large number of scientific outcomes have revealed that reduction of P loss to surface water bodies is one of the main factors for obtaining higher quality of fresh-and seawaters, which must result in new EU directives also focussed in nonpoint pollution related to P load.
Objective. To investigate 1 functional (rs17266594) and 2 potentially functional (rs10516487 and rs3733197) BANK1 variants, which were previously identified as systemic lupus erythematosus (SLE) susceptibility markers, to test whether they are associated with rheumatoid arthritis (RA).Methods. Four different cohorts were included in the study: 1,080 RA patients and 1,368 healthy controls from Spain, 278 RA patients and 568 healthy controls from Sweden, 288 RA patients and 287 healthy controls from Argentina, and 288 RA patients and 288 healthy controls from Mexico. Samples were genotyped for BANK1 single-nucleotide polymorphisms (SNPs) using a TaqMan 5-allele discrimination assay. Statistical analysis comparing allele and genotype distributions was performed with the chi-square test.Results. We did not find a significant association between RA and the rs10516487 and rs17266594 BANK1 polymorphisms. However, there was an increase in the major alleles among RA patients. Similarly, for rs3733197, there was an increase in the major allele among patients in every cohort. Conclusion. These results suggest that BANK1 SNPs and haplotypes may contribute to RA susceptibility with a low risk.
Rhizosphere microbes may enhance nutrient uptake by plants. Here we studied the effect of Trichoderma asperellum inoculation on the uptake of Fe, Cu, Mn, and Zn by wheat (Triticum aestivum L) grown in a calcareous medium. To this end, an experiment involving two factors, namely Fe enrichment (ferrihydrite enrichment and non-enrichment of the growing medium), and inoculation/non-inoculation with Trichoderma asperellum strain T34, was performed twice under the same conditions. The increase in Fe availability as a result of ferrihydrite enrichment did not enhance plant dry matter production. The effect of T34 on the concentration of Fe, Cu, Mn and Zn, and the total amount of Cu, Mn, and Zn in the aerial parts differed depending on the degree of ferrihydrite enrichment. Inoculation with T34 increased Fe concentration in Fe-deficient media, thus revealing a positive effect of this microorganism on Fe nutrition in wheat. However, T34 significantly decreased the concentration and total amount of Cu, Mn, and Zn in the aerial parts, but only in ferrihydrite-enriched medium. This adverse effect of T34 on Cu, Mn, and Zn uptake by wheat plants may have been related to conditions of restricted availability where potential competition for nutrients between microorganisms and plants can be more marked.
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