Azotobacter vinelandii is a diazotrophic bacterium characterized by the outstanding capability of storing Mo in a special storage protein, which guarantees Mo-dependent nitrogen fixation even under growth conditions of extreme Mo starvation. The Mo storage protein is constitutively synthesized with respect to the nitrogen source and is regulated by molybdenum at an extremely low concentration level (0-50 nM). This protein was isolated as an alpha4beta4 octamer with a total molecular mass of about 240 kg mol(-1) and its shape was determined by small-angle X-ray scattering. The genes of the alpha and beta subunits were unequivocally identified; the amino acid sequences thereby determined reveal that the Mo storage protein is not related to any other known molybdoprotein. Each protein molecule can store at least 90 Mo atoms. Extended X-ray absorption fine-structure spectroscopy identified a metal-oxygen cluster bound to the Mo storage protein. The binding of Mo (biosynthesis and incorporation of the cluster) is dependent on adenosine triphosphate (ATP); Mo release is ATP-independent but pH-regulated, occurring only above pH 7.1. This Mo storage protein is the only known noniron metal storage system in the biosphere containing a metal-oxygen cluster.
Objective. To report on referral patterns of primary physicians for children subsequently diagnosed with juvenile idiopathic arthritis (JIA) and to identify predictors of delayed referral to a pediatric rheumatology center. Methods. A retrospective cohort study of consecutive patients with JIA referred to a pediatric rheumatology center over a 15-year period was performed. Variables included age, sex, JIA subtype, the physician's subspecialty, and distance to the pediatric rheumatology center. Outcome parameters were the time to first presentation to a primary physician, the time to the first rheumatology visit, and the total time to referral. Putative predictors were evaluated by analysis of variance, resulting in regression models. Results. A total of 132 patients with JIA were included; 83 (63%) were female. The median age at the onset of symptoms was 4.5 years (range 1.0 -15.8 years). Most frequently, children were referred by pediatricians (49.4%) or orthopedic surgeons (34.1%). The median time to first presentation was short at 10 days (range 0 -1,610 days). In contrast, the median time to first rheumatology visit was 60 days (range 0.0 -2,100.0 days), resulting in a long median total time to referral of 90 days (range 0.0 -2,160.0 days). Statistically significant predictors for delayed referral were the primary physician's subspecialty (P ؍ 0.016) and the distance to the pediatric rheumatology center (P ؍ 0.001). Children living in remote areas or referred by orthopedic surgeons had the longest referral times. Conclusion. Despite free access to health care in Germany, children with JIA are referred to pediatric rheumatology centers with significant delay. Educational interventions targeting primary physicians and orthopedic surgeons may contribute to earlier referral to pediatric rheumatology centers and improve outcome in patients with JIA.
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