Encapsulation within poly(ethylene glycol)-b-poly(propylene sulfide) micelles reduces the toxicity of celastrol and enhances its anti-inflammatory effect during treatment of atherosclerosis.
There are similarities and differences in genetic susceptibility for SLE between Caucasian and Asian ethnic groups. Although 16 putative novel loci for SLE have been suggested in the Korean population, further research on a larger sample is required to discriminate truth from error.
Objective. To investigate whether a human X chromosome locus of IRAK1 and MECP2 is associated with susceptibility to rheumatoid arthritis (RA), an autoimmune disease that predominantly affects women.Methods. A total of 2,334 unrelated Korean participants (including 1,318 patients with RA) were genotyped for 5 tag single-nucleotide polymorphisms (SNPs) and 3 additional SNPs in an Xq28 region harboring MECP2 and IRAK1. Twenty-nine additional neighboring SNPs were imputed using the Korean HapMap Project data. All 37 SNPs were statistically tested for association with RA susceptibility, and 2 SNPs associated with RA were examined for their functional effects.Results. RA susceptibility was associated with multiple SNPs in a 79-kb linkage disequilibrium block harboring both MECP2 and IRAK1. The most significant association was for MECP2 SNP rs1734792 (P ؍ 0.00089), but 2 nonsynonymous IRAK1 SNPs, rs1059702 (P ؍ 0.0034) and rs1059703 (P ؍ 0.0042), which were in strong linkage disequilibrium with the MECP2 SNP (D ؍ 0.87 and 0.91, respectively) affected IRAK1 protein activity. The major haplotype of the 2 nonsynonymous SNPs was associated with a 1.7-fold increase in RA susceptibility versus the minor haplotype (P ؍ 0.0082), and with increased IRAK1 activity, which was demonstrated by a 1.7-fold increase in the intracellular activity of transcription factor NF-B.Conclusion. Our findings indicate that RA susceptibility is associated with multiple SNPs in MECP2 and IRAK1, but high linkage disequilibrium between them does not allow for further localization. Therefore, both genes remain candidates. Nevertheless, the major haplotype of the 2 nonsynonymous IRAK1 SNPs encoding for pPhe196Ser and pSer532Leu confers enhanced IRAK1 activity and, consequently, enhanced susceptibility to RA, as compared to the minor haplotype.
The effect of boundary layer separation on worker exposure is an important factor in the design of local exhaust ventilation. Three-dimensional airflow around a mannequin is examined by using flow visualization techniques and hot-film anemometry. Above the chest, a downwash effect is noted; from the chest to the elbows, a combination of downwash and vortex shedding is observed; and from the waist to the hip, vortex shedding appears to be dominant. A coherent vertical flow structure is observed close to the body. Vortex shedding frequency is determined by using hot-film anemometry. The dimensions of the reverse flow region and the area of the vortices are estimated from flow visualization videos.
Clinical risk factors (CRFs), with or without bone mineral density (BMD), are used to determine the risk of osteoporotic fracture (OF), which has a heritable component. In this study we investigated whether genetic profiling can additionally improve the ability to predict OF. Using 1229 unrelated Korean postmenopausal women, 39 single-nucleotide polymorphisms (SNPs) in 30 human genomic loci were tested for association with osteoporosis-related traits, such as BMD, osteoporosis, vertebral fracture (VF), nonvertebral fracture (NVF), and any fracture. To estimate the effects of genetic profiling, the genetic risk score (GRS) was calculated using five prediction models: (Model I) GRSs only; (Model II) BMD only; (Model III) CRFs only; (Model IV) CRFs and BMD; and (Model V) CRFs, BMD, and GRS. A total of 21 SNPs within 19 genes associated with one or more osteoporosis-related traits and were included for GRS calculation. GRS associated with BMD before and after adjustment for CRFs (p ranging from <0.001 to 0.018). GRS associated with NVF before and after adjustment for CRFs and BMD (p ranging from 0.017 to 0.045), and with any fracture after adjustment for CRFs and femur neck BMD (p ¼ 0.049). In terms of predicting NVF, the area under the receiver operating characteristic curve (AUC) for Model I was 0.55, which was lower than the AUCs of Models II (0.60), III (0.64), and IV (0.65). Adding GRS to Model IV (in Model V) increased the AUC to 0.67, and improved the accuracy of NVF classification by 11.5% (p ¼ 0.014). In terms of predicting any fracture, the AUC of Model V (0.68) was similar to that of Model IV (0.68), and Model V did not significantly improve the accuracy of any fracture classification (p ¼ 0.39). Thus, genetic profiling may enhance the accuracy of NVF predictions and help to delineate the intervention threshold.
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