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Vance Creech posted an update 5 months, 4 weeks ago
We have previously reported that quinoline increased the mutation frequency of the cII gene in the liver of lambda/lacZ transgenic mice (Muta™Mouse), and GC to CG transversions were the molecular signature of quinoline-induced mutations. 4-Methylquinoline (4-MeQ) has the highest mutagenicity among quinoline and isomeric methylquinolines according to the Ames test using Salmonella typhimurium TA 100, in the presence of rat liver microsomal enzymes. In this report, we examined the effect of 4-MeQ on mutagenesis in the lambda cII gene in the liver of the Muta™Mouse, and we analyzed the sequences of the mutated genes. The mutation frequency of the liver cII gene was seven times higher in 4-MeQ-treated mice than in control mice. Sequence analysis revealed that 4-MeQ primarily induced GC to CG transversions (37 of 45). The specificities of 4-MeQ for target organ and mutation pattern were very consistent with those of quinoline. Thus, we showed that 4-MeQ was also genotoxic in the liver of the Muta™Mouse, and as with quinoline, the GC to CG transversion was the molecular signature of the 4-MeQ-induced mutations.A detailed understanding of the role of Tfh cells in MuSK-antibody positive myasthenia gravis (MuSK-MG) is lacking. We characterized phenotype and function of Tfh cells in MuSK-MG patients and controls. We found similar overall Tfh and follicular regulatory (Tfr) T cell frequencies in MuSK-MG and healthy controls, but MuSK-MG patients exhibited higher frequencies of Tfh17 cells and a higher ratio of TfhTfr cells. These results suggest imbalanced Tfh cell regulation, further supported by increased frequencies of CD4 T cells co-producing IL-21/IL-17 and IL-17/IFN-γ, and increased Tfh-supported IgG production. These results support a role for Tfh cell dysregulation in MuSK-MG immunopathology.Background Several studies have investigated the association between selenium levels and skin diseases, but reached inconsistent results. Objective This systematic review and meta-analysis was conducted to evaluate the association between selenium levels and skin diseases. Methods A systematic search was conducted in public databases to identify all relevant studies, and study-specific standard mean differences (SMD) and 95% confidence intervals (CI) were pooled to compare the selenium levels between different groups. Results Twenty-seven studies were identified with a total of 1315 patient and 7181 healthy controls. Compared with controls, no significant difference in selenium was found in patients with vitiligo (SMD = 0.53, 95% CI -0.40 to 1.45), alopecia areata (SMD = 0.47, 95% CI -2.72 and 3.65), or eczema (SMD = 0.12, 95% CI -0.24 to 0.48). A lower selenium level was found in patients with psoriasis (SMD = -0.62, 95% CI -1.15 to -0.10), acne vulgaris (SMD = -1.02, 95% CI -1.45 to -0.60), chloric acne (SMD = -2.35, 95% CI -3.15 to -1.55), and atopic dermatitis (SMD = -2.62, 95% CI -3.00 to -2.24). As for disease severity, severe patients had a higher selenium level than mild patients in psoriasis (SMD = 0.72, 95% CI 0.07-1.38), but no difference was found in vitiligo (SMD = -0.26, 95% CI -2.38 to 1.85) and alopecia areata (SMD = 0.46, 95% CI -0.34 to 1.26). Conclusion Selenium levels were associated with several skin diseases and the disease severity, and high selenium levels tended to be a protective factor in certain skin diseases.Purpose We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis , psoriatic arthritis , inflammatory bowel disease , Behçet disease , granulomatosis with polyangiitis , microscopic polyangiitis , systemic lupus erythematosus and axial spondyloarthritis ). Besides topical and oral systemic glucocorticoids, patients had received methylprednisolone pulses , and conventional immunosuppressive drugs, mainly methotrexate , and leflunomide . Eleven patients had required ocular surgery prior to biologic therapy. Methods Following biologic therapy, baseline main outcr adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.Background Lag screw osteosynthesis in odontoid fractures shows a high rate of pseudarthrosis. Biomechanical properties may play a role with insufficient fragment compression or unnoticed screw stripping. A biomechanical comparison of different constructed lag-screws was carried out and the biomechanical properties determined. Methods Two identical compression screws with different pilot holes (1.25 and 2.5 mm), a double-threaded screw and one sleeve-nut-screw were tested on artificial bone (Sawbone, densities 10-30pcf). Fragment compression and torque were continuously measured using thin-film force sensors (Flexiforce A201, Tekscan) and torque sensors (PCE-TM 80, PCE GmbH). Findings The lowest compression reached the double-threaded screw. Compression and sleeve-nut-screw achieved 214-298% and 325-546%, respectively, of the compression force of double-threaded-screw, depending on the test material. EIDD-1931 The pilot hole optimization led to a significant improvement in compression only in the densest test material. Screw stripping took place significantly later with increasing density of the test material on all screws. In compression screws this was done at a screw rotation of 180-270°, in sleeve nut screw at 270-720° and in double-threaded screws at 300-600° after reaching the maximum compression. Interpretation Double-threaded screw is robust against screw stripping, but achieves only low fragment compression. The classic compression screws achieve better compression, but are sensitive to screw stripping. Sleeve-nut screw is superior in compression and as robust as double-threaded screw against screw stripping. Whether the better biomechanical properties lead to a reduction in pseudarthrosis must be proven in clinical trials.