Objective To identify a genetic cause of early-onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of disease. Methods We performed whole exome sequencing (WES) and SNP array genotyping in affected and unaffected family members. Protein studies, gene expression, cytokine profiling, neutrophil extracellular trap formation, and presence of low-density granulocytes were evaluated in patient primary cells and serum samples. Results We identified a novel homozygous loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Sanger sequencing of 14 family members confirmed the homozygous mutation in four affected patients, and in an asymptomatic 9-year old female. Sera from patients with truncated C1r protein had low complement levels. Two affected siblings available for detailed evaluation exibited strong type I interferon inflammatory signatures despite being clinically inactive at the time of sampling. The type-I IFN transcriptional signature in patients’ blood correlated with disease expressivity, whereas the neutrophil signature in patients’ PBMCs was likely associated with disease severity. The affected female with the most severe phenotype, showed a stronger neutrophil signature, defined by enhanced neutrophil extracellular trap formation and the presence of low-density granulocytes. Analysis of exome data for modifying alleles suggested enrichment of common SLE-associated variants in the more severely affected patients. Lupus-associated HLA alleles or HLA haplotypes were not shared among the 4 affected subjects. Conclusion We report a novel high-penetrance mutation in C1R as the cause of monogenic SLE. Disease expressivity in this family appears to be influenced by additional common and rare genetic variants.
BackgroundIn this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF).MethodsIn this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement.ResultsA total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group.ConclusionsUsing colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage.Trial Registration IDClinicalTrials.gov identifier NCT02602028. Registered 5 November 2015.
In this study, the optimum blend rate and injection pressure in a four-stroke, single cylinder, direct injection diesel engine using soybean methyl ester were investigated experimentally. The tests were conducted at two stages. Firstly, the engine was tested with diesel fuel, B25 (25% biodiesel + 75% diesel fuel), B50, B75, and B100 fuels at full load and at a constant speed. According to the test results, it was determined that the most suitable fuel was B25 in terms of performance and emission. Secondly, the engine was tested at different loads with diesel fuel at original injection pressure and with B25 at different injection pressures (160, 180, 200, 220, and 240 bar) for comparison. It was determined from tests performed with B25 that the most suitable injection pressure in terms of performance and emissions was 220 bar. The specific fuel consumption and power values of the B25 were found to be nearly the same as those of diesel fuel at 220 bar injection pressure. In addition, HC, CO, and smoke emissions were reduced by about 33%, 9%, and 20%, respectively. On the other hand, NO x emission increased by about 12%.
A rational management of children and adolescents with rheumatic and autoinflammatory diseases requires the regular assessment of the level of disease activity and of child health and well-being through the use of well-validated outcome measures. Ideally, such instruments should be simple and feasible and easily applicable in standard clinical practice. In recent years, a number of novel outcome measures have been developed and validated for use in pediatric patients with rheumatic and autoinflammatory illnesses. Furthermore, there has been an increased focus on the appraisal of child and parent perception of the disease impact. The new tools have markedly enlarged the spectrum of disorders and health domains that can be assessed in a standardized way. This progress will help to enhance the reliability of research studies and clinical trials. The aim of the present review is to provide an update of the recent advances in this field of research.
Bu çalışmada, biyodizel içerisine iki farklı oranda (%10, %20) propanol alkolü ilave edilmiş ve tek silindirli dizel motorda test edilmiştir. Elde edilen sonuçlarda biyodizel yakıtına göre motor performansında iyileşme olduğu görülmüştür. CO, NO x ve is emisyonlarının azalma eğiliminde olduğu fakat HC emisyonlarında ise artış olduğu tespit edilmiştir. Biyodizel içerisinde propanol ilavesi ile biyodizel yakıtının bazı dezavantajlarının ortadan kaldırılabileceği ve özellikle NO x emisyonlarında iyileşme olduğu belirlenmiştir.
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