Scrub typhus is a potentially fatal infectious disease. However, to this date, no epidemiologic study on mortality of complicated scrub typhus has been reported. We reviewed the clinical records of 302 patients with diagnosis of scrub typhus who were admitted to our institute between January 2000 and December 2006. In total, 297 patients with scrub typhus were analyzed and the mortality rate of this study group was 6.1%. Multivariate logistic regression analysis revealed absence of eschar, event of intensive care unit admission and higher APACHE II score were independent predictive variables. Identification of these risk factors leading to fatal outcome may help physicians to start early intensive management of complicated scrub typhus.

To evaluate the involvement of translation initiation factors eIF4E and eIFiso4E in Chilli veinai mottle virus (ChiVMV) infection in pepper, we conducted a genetic analysis using a segregating population derived from a cross between Capsicum annuum 'Dempsey' containing an eIF4E mutation (pvr1(2)) and C. annuum 'Perennial' containing an eIFiso4E mutation (pvr6). C. annuum 'Dempsey' was susceptible and C. annuum 'Perennial' was resistant to ChiVMV. All F(1) plants showed resistance, and F(2) individuals segregated in a resistant-susceptible ratio of 166:21, indicating that many resistance loci were involved. Seventy-five F(2) and 329 F(3) plants of 17 families were genotyped with pvr1(2) and pvr6 allele-specific markers, and the genotype data were compared with observed resistance to viral infection. All plants containing homozygous genotypes of both pvr1(2) and pvr6 were resistant to ChiVMV, demonstrating that simultaneous mutations in eIF4E and eIFiso4E confer resistance to ChiVMV in pepper. Genotype analysis of F2 plants revealed that all plants containing homozygous genotypes of both pvr1(2) and pvr6 showed resistance to ChiVMV. In protein-protein interaction experiments, ChiVMV viral genome-linked protein (VPg) interacted with both eIF4E and eIFiso4E. Silencing of eIF4E and eIFiso4E in the VIGS experiment showed reduction in ChiVMV accumulation. These results demonstrated that ChiVMV can use both eIF4E and eIFiso4E for replication, making simultaneous mutations in eIF4E and eIFiso4E necessary to prevent ChiVMV infection in pepper.

oxide could be supplied to the local wound area through the systemic blood circulation because topical tacrolimus does not reduce blood nitric oxide level.In conclusion, topically-treated tacrolimus does not have a negative effect on wound healing. Acknowledgements Conflict of interestsThe authors declare no conflict of interest. References1 Liu J, Albers M W, Wandless T J et al.

Identifying host factors provides an important clue to understand virus infection. We selected 10 host factor candidate genes and each gene was silenced in Nicotiana benthamiana (N. benthamiana) to investigate their roles in virus infection. The resulting plants were infected with Tobacco mosaic virus (TMV). The accumulation of viral coat protein and the spread of virus were greatly reduced in the plants that eukaryotic translation elongation factor 1A (eEF1A) or 1B (eEF1B) was silenced. These results suggest both eEF1A and eEF1B are required for TMV infection. We also tested for interactions between the eEFs and viral proteins of TMV. Both eEF1A and eEF1B proteins interacted directly with the methyltransferase (MT) domain of the TMV RNA-dependent RNA polymerase (RdRp). eEF1A and eEF1B also interacted with each other in vivo. Our data suggest that eEF1B may be a component of the TMV replication complex which interacts with MT domain of TMV RdRp and eEF1A.

BACKGROUND AND PURPOSENF-kB has been implicated as a therapeutic target for the treatment of rheumatoid arthritis. We previously synthesized a thiourea analogue, SPA0355, which suppressed NF-kB activity. Here we have assessed the anti-inflammatory and anti-arthritic effects of SPA0355. EXPERIMENTAL APPROACHWe evaluated the effects of SPA0355 on human rheumatoid fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in mice in vivo. KEY RESULTSIn vitro experiments demonstrated that SPA0355 suppressed chemokine production, matrix metalloproteinase secretion and cell proliferation induced by TNF-a in rheumatoid fibroblast-like synoviocytes. In addition, SPA0355 inhibited osteoclast differentiation induced by macrophage colony-stimulating factor and the receptor activator of NF-kB ligand, in bone marrow macrophages. Mice with CIA that were pretreated with SPA0355 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiological and histopathological findings, and inflammatory cytokine levels, than mice treated with vehicle. Mice treated with SPA0355, after the onset of CIA, also showed significantly decreased disease incidence and joint oedema. The in vitro and in vivo protective effects of SPA0355 were mediated by inhibition of the NF-kB signalling pathway. CONCLUSION AND IMPLICATIONSTaken together, these results suggested that using SPA0355 to block the NF-kB pathway in rheumatoid joints reduced both the inflammatory responses and tissue destruction. Therefore, SPA0355 may have therapeutic value in preventing or delaying joint destruction in patients with rheumatoid arthritis.