Inflammatory perivascular cuffs are comprised of leucocytes that accumulate in the perivascular space around post-capillary venules before their infiltration into the parenchyma of the central nervous system. Inflammatory perivascular cuffs are commonly found in the central nervous system of patients with multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis. Leucocytes that accumulate in the perivascular space secrete matrix metalloproteinases that aid their transmigration into the neural parenchyma. We described previously that the upstream inducer of matrix metalloproteinase expression, extracellular matrix metalloproteinase inducer (CD147), was elevated in experimental autoimmune encephalomyelitis, and that its inhibition reduced leucocyte entry into the central nervous system. Here we investigated whether the expression of extracellular matrix metalloproteinase inducer varies with the temporal evolution of lesions in murine experimental autoimmune encephalomyelitis, whether it was uniformly upregulated across multiple sclerosis specimens, and whether it was a feature of inflammatory perivascular cuffs in multiple sclerosis lesions. In experimental autoimmune encephalomyelitis, elevation of extracellular matrix metalloproteinase inducer was correlated with the appearance and persistence of clinical signs of disease. In both murine and human samples, extracellular matrix metalloproteinase inducer was detected on endothelium in healthy and disease states but was dramatically increased in and around inflammatory perivascular cuffs on leucocytes, associated with matrix metalloproteinase expression, and on resident cells including microglia. Leucocyte populations that express extracellular matrix metalloproteinase inducer in multiple sclerosis lesions included CD4 + and CD8 + T lymphocytes, B lymphocytes and monocyte/macrophages. The extra-endothelial expression of extracellular matrix metalloproteinase inducer was a marker of the activity of lesions in multiple sclerosis, being present on leucocyte-containing perivascular cuffs but not in inactive lesions. By using a function-blocking antibody, we implicate extracellular matrix metalloproteinase inducer in the adhesion of leucocytes to endothelial cells and determined that its activity was more crucial on leucocytes than on endothelium in leucocyte-endothelial cell engagement in vitro. Extracellular matrix metalloproteinase inducer activity regulated the level of alpha 4 integrin on leucocytes through a mechanism associated with nuclear factor kB signalling. Blocking extracellular matrix metalloproteinase inducer attenuated the transmigration of monocytes and B lymphocytes across a model of the blood-brain barrier in culture. In summary, we describe the prominence of extracellular matrix metalloproteinase inducer in central nervous system inflammatory perivascular cuffs, emphasize its dual role in matrix metalloproteinase induction and leucocyte adhesion, and highlight the elevation of extracellular matrix metalloproteinase inducer...
Introduction We examined the effect of bicycle helmet fit and position on head and facial injuries. Methods Cases were helmeted cyclists with a head (n = 297) or facial (n = 289) injury. Controls were helmeted cyclists with other injuries, excluding the neck. Participants were interviewed in seven Alberta emergency departments or by telephone; injury data were collected from charts. Missing values were imputed using chained equations and custom prediction imputation models. Results Compared with excellent helmet fit, those with poor fit had increased odds of head injury (odds ratio [OR] = 3.38, 95% confidence interval [CI]: 1.06–10.74). Compared with a helmet that stayed centred, those whose helmet tilted back (OR = 2.90, 95% CI: 1.54–5.47), shifted (OR = 1.91, 95% CI: 1.01–3.63) or came off (OR = 6.72, 95% CI: 2.86–15.82) had higher odds of head injury. A helmet that tilted back (OR = 4.81, 95% CI: 2.74–8.46), shifted (OR = 1.83, 95% CI: 1.04–3.19) or came off (OR = 3.31, 95% CI: 1.24–8.85) also increased the odds of facial injury. Conclusion Our findings have implications for consumer and retail education programs.
Introduction:Training cardiac sonographers is a lengthy process involving a large commitment of time and resources. By facilitating successful trainee outcomes, accreditation can be achieved in the shortest time possible. The purpose of this observational piece is to highlight potential barriers to the timely completion of cardiac sonographer training leading to accreditation as a medical sonographer.
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