Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever

Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/µL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF

Fabrication of Textured Porous Ti3SiC2 by Slip Casting under High Magnetic Field and Microstructural Evolution through High Temperature Deformation

To clarify the effect of constraint conditions on the kink formation, fabrication process of the texture and porosity controlled Ti3SiC2 polycrystals was investigated and microstructural evolution during high temperature deformation was examined in it under high temperature uniaxial compression tests at 1200 degrees C. Dense textured Ti3SiC2 sintered body was fabricated by slip casting in the high magnetic field of 12 T and following pressureless sintering at 1400 degrees C for 1 h. The porosity of the textured Ti3SiC2 was controlled by dispersing polymethyl methacrylate (PMMA) particles into the textured Ti3SiC2 as a spacer media. The highly textured Ti3SiC2 polycrystals with porosity of 8.4 vol% and 16.7 vol%, respectively, were successfully fabricated by the slip casting in the high magnetic field. After the high temperature uniaxial compression perpendicular to the c-axis of the textured structure, both the porous and dense Ti3SiC2 showed kink formation, which is a common deformation mode for anisotropic layered materials. However, the average rotation angles of the kink boundaries were higher in the porous specimen than in the dense specimen. Since the crystal rotation is necessary for the kink formation, kink bands would be preferably developed in the porous area due to its weaker constraint than in the dense area. It can be concluded from the microstructural analysis that the constrain factor caused by the neighbor grains affects the crystalline rotation, resulting in the kink boundary formation with different rotation angles

Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype.

Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1) mutations. PTCH1 is a hedgehog (Hh) receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported. Recently, mutations in Suppressor of fused homolog (SUFU) or PTCH2 were reported in patients with Gorlin syndrome. These facts suggest that multi-layered mutations in Hh pathway may contribute to the development of Gorlin syndrome. We demonstrated multiple mutations of Hh-related genes in addition to PTCH1, which possibly act in an additive or multiplicative manner and lead to Gorlin syndrome. High-throughput sequencing was performed to analyze exome sequences in four unrelated Gorlin syndrome patient genomes. Mutations in PTCH1 gene were detected in all four patients. Specific nucleotide variations or frameshift variations of PTCH1 were identified along with the inferred amino acid changes in all patients. We further filtered 84 different genes which are closely related to Hh signaling. Fifty three of these had enough coverage of over ×30. The sequencing results were filtered and compared to reduce the number of sequence variants identified in each of the affected individuals. We discovered three genes, PTCH2, BOC, and WNT9b, with mutations with a predicted functional impact assessed by MutationTaster2 or PolyPhen-2 (Polymorphism Phenotyping v2) analysis. It is noticeable that PTCH2 and BOC are Hh receptor molecules. No significant mutations were observed in SUFU. Multi-layered mutations in Hh pathway may change the activation level of the Hh signals, which may explain the wide phenotypic variability of Gorlin syndrome