Gli2, hedgehog and TCR signalling

Editoria

Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma

The pathophysiology of allergic asthma is driven by T-helper 2 (Th2) immune responses following aeroallergen inhalation. The mechanisms that initiate, potentiate and regulate airways allergy are incompletely characterized. We have previously shown that Hedgehog (Hh) signaling to T-cells, via downstream Gli transcription factors, enhances T-cell conversion to a Th2 phenotype. Here, we show for the first time that Gli-dependent transcription is activated in T-cells in vivo during murine allergic airways disease (AAD) a model for the immunopathology of asthma; and that genetic repression of Gli signaling in Tcells decreases the differentiation and/or recruitment of Th2 cells to the lung. We report that T-cells are not the only cells capable of expressing activated Gli during AAD. A substantial proportion of eosinophils and lung epithelial cells, both central mediators of the immunopathology of asthma, are also able to undergo Hh/Gli signaling. Finally, we show that Shh increases Il4 expression in eosinophils. We therefore propose that Hh signaling during AAD is complex, involving multiple cell types, signaling in an auto- or paracrine fashion. Improved understanding of the role of this major morphogenetic pathway in asthma may give rise to new drug targets for this chronic condition

Summary and recommendations

According to Carpenter (1993), the first problem for nutritional science, to identify the chemicals required in a diet to support human growth and maintenance, has been solved. Enough information has been amassed from the study of many populations to enable nutritionists to offer safe recommendations about daily intakes of energy and nutrients for all stages of the human life cycle (see reviews by Nesheim and by Solomons, this volume). Adoption of these recommendations would generally correct deficiency diseases and would reduce the incidence of health complications which are linked to excessive intakes of fat, sodium, alcohol and other substances. Carpenter also drew attention to malnutrition, the solution of which he believed to have become largely political and economic although the fact remains that very many people still do not receive or grow enough food. In the context of this volume, Carpenter's most interesting point was his view that our understanding of the complex relationship between nutrition and disease was still at an early stag

Do hip precautions after posterior-approach total hip arthroplasty affect dislocation rates? A systematic review of 7 studies with 6,900 patients

Background and purpose — Hip precautions limiting flexion, adduction, and internal rotation have been prescribed traditionally to minimize dislocation rates following THA. We assessed the prevalence of hip dislocation following posterior approach total hip arthroplasty without postoperative hip precautions. Methods — A systematic review of multiple medical databases was performed using the PRISMA guidelines and checklist. All clinical outcome studies that reported dislocation rates and postoperative instructions following posterior approach, primary surgery, published within the last 6 years, were included. Results — 6,900 patients were included from 7 Level I–IV studies, with 3,517 treated with and 3,383 without precautions. There was no statistically significant difference in the rates of dislocation between groups (2.2% in restricted group vs. 2.0% in unrestricted group). All but 1 study demonstrated no statistically significant differences in patient-reported outcome scores between restricted and unrestricted groups, including those pertaining to return to function, confidence, and pain. Interpretation — The review found no impact on dislocation rates following total hip arthroplasty performed through a posterior approach, regardless of the use of hip precautions. We also found no impact of the prescription of hip precautions on patient-reported outcome scores

A scanning drift tube apparatus for spatio-temporal mapping of electron swarms

A "scanning" drift tube apparatus, capable of mapping of the spatio-temporal evolution of electron swarms, developing between two plane electrodes under the effect of a homogeneous electric field, is presented. The electron swarms are initiated by photoelectron pulses and the temporal distributions of the electron flux are recorded while the electrode gap length (at a fixed electric field strength) is varied. Operation of the system is tested and verified with argon gas, the measured data are used for the evaluation of the electron bulk drift velocity. The experimental results for the space-time maps of the electron swarms - presented here for the first time - also allow clear observation of deviations from hydrodynamic transport. The swarm maps are also reproduced by particle simulations

Needs Assessment: Taking the Pulse of the Public Recreation Client.

38 p