Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75065/1/j.1365-2982.2004.00524.x.pd

Emergency vaccination of rabies under limited resources – combating or containing?

BACKGROUND: Rabies is the most important viral zoonosis from a global perspective. Worldwide efforts to combat the disease by oral vaccination of reservoirs have managed to eradicate wildlife rabies in large areas of central Europe and North-America. Thus, repeated vaccination has been discontinued recently on a geographical scale. However, as rabies has not yet been eradicated globally, a serious risk of re-introduction remains. What is the best spatial design for an emergency vaccination program – particularly if resources are limited? Either, we treat a circular area around the detected case and run the risk of infected hosts leaving the limited control area, because a sufficient immunisation level has not yet been built up. Or, initially concentrate the SAME resources in order to establish a protective ring which is more distant from the infected local area, and which then holds out against the challenge of the approaching epidemic. METHODS: We developed a simulation model to contrast the two strategies for emergency vaccination. The spatial-explicit model is based on fox group home-ranges, which facilitates the simulation of rabies spread to larger areas relevant to management. We used individual-based fox groups to follow up the effects of vaccination in a detailed manner. Thus, regionally – bait distribution orientates itself to standard schemes of oral immunisation programs and locally – baits are assigned to individual foxes. RESULTS: Surprisingly, putting the controlled area ring-like around the outbreak does not outperform the circular area of the same size centred on the outbreak. Only during the very first baitings, does the ring area result in fewer breakouts. But then as rabies is eliminated within the circle area, the respective ring area fails, due to the non-controlled inner part. We attempt to take advantage of the initially fewer breakouts beyond the ring when applying a mixed strategy. Therefore, after a certain number of baitings, the area under control was increased for both strategies towards the same larger circular area. The circle-circle strategy still outperforms the ring-circle strategy and analysis of the spatial-temporal disease spread reveals why: improving control efficacy by means of a mixed strategy is impossible in the field, due to the build-up time of population immunity. CONCLUSION: For practical emergency management of a new outbreak of rabies, the ring-like application of oral vaccination is not a favourable strategy at all. Even if initial resources are substantially low and there is a serious risk of rabies cases outside the limited control area, our results suggest circular application instead of ring vaccination

Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα\alpha expression requires TRIF and MyD88

TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-κB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absence of TRIF, impairs NF-κB translocation. We tested the model proposed by Cheng et al. using real-time single cell analysis in macrophages expressing EGFP-tagged p65 and a TNF$\alpha$ promoter-driven mCherry. Following LPS stimulation, cells lacking TRIF show a pattern of NF-κB dynamics that is unaltered from wild-type cells, but activation of the TNF$\alpha$ promoter is impaired. In macrophages lacking MyD88, there is minimal NF-κB translocation to the nucleus in response to LPS stimulation, and there is no activation of the TNF$\alpha$ promoter. These findings confirm that signalling through MyD88 is the primary driver for LPS-dependent NF-κB translocation to the nucleus. The pattern of NF-κB dynamics in TRIF-deficient cells does not, however, directly reflect the kinetics of TNF$\alpha$ promoter activation, supporting the concept that TRIF-dependent signalling plays an important role in the transcription of this cytokine.J.S. is supported by the Cambridge Commonwealth, European and International Trust. CEB was supported by a BBSRC fellowship (BB/H021930/1) and a Wellcome Trust Investigator award (WT108045AIA). E.C. and P.C. acknowledge EU-ITN Transpol and EU-ERC Hydrosync. I.D.C.F. is supported by the intramural Research Program of the National Institute of Allergy and Infectious Diseases

ICAR: endoscopic skull‐base surgery

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