Why do walk-in patients prefer a busy urban emergency department during office hours? A pilot survey of 200 consecutive patients from Switzerland

In Switzerland, more and more patients go directly to the emergency department, bypassing general practitioners. However, a mixture of non-urgent walk-in patients and acute emergencies in the same emergency department can inevitably make it more difficult to provide genuine emergencies with rapid treatment, leading to deterioration in the quality of emergency services, and tending to increase on-floor mortality and morbidity, together with higher overall costs.

How much is there really? Why stereology is essential in lung morphometry

Quantitative data on lung structure are essential to set up structure-function models for assessing the functional performance of the lung or to make statistically valid comparisons in experimental morphology, physiology, or pathology. The methods of choice for microscopy-based lung morphometry are those of stereology, the science of quantitative characterization of irregular three-dimensional objects on the basis of measurements made on two-dimensional sections. From a practical perspective, stereology is an assumption-free set of methods of unbiased sampling with geometric probes, based on a solid mathematical foundation. Here, we discuss the pitfalls of lung morphometry and present solutions, from specimen preparation to the sampling scheme in multiple stages, for obtaining unbiased estimates of morphometric parameters such as volumes, surfaces, lengths, and numbers. This is demonstrated on various examples. Stereological methods are accurate, efficient, simple, and transparent; the precision of the estimates depends on the size and distribution of the sample. For obtaining quantitative data on lung structure at all microscopic levels, state-of-the-art stereology is the gold standard.

Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is essential for the local activation of glucocorticoid receptors (GR). Unlike unliganded cytoplasmic GR, 11beta-HSD1 is an endoplasmic reticulum (ER)-membrane protein with lumenal orientation. Cortisone might gain direct access to 11beta-HSD1 by free diffusion across membranes, indirectly via intracellular binding proteins or, alternatively, by insertion into membranes. Membranous cortisol, formed by 11beta-HSD1 at the ER-lumenal side, might then activate cytoplasmic GR or bind to ER-lumenal secretory proteins. Compartmentalization of 11beta-HSD1 is important for its regulation by hexose-6-phosphate dehydrogenase (H6PDH), which regenerates cofactor NADPH in the ER lumen and stimulates oxoreductase activity. ER-lumenal orientation of 11beta-HSD1 is also essential for the metabolism of the alternative substrate 7-ketocholesterol (7KC), a major cholesterol oxidation product found in atherosclerotic plaques and taken up from processed cholesterol-rich food. An 11beta-HSD1 mutant adopting cytoplasmic orientation efficiently catalyzed the oxoreduction of cortisone but not 7KC, indicating access to cortisone from both sides of the ER-membrane but to 7KC only from the lumenal side. These aspects may be relevant for understanding the physiological role of 11beta-HSD1 and for developing therapeutic interventions to control glucocorticoid reactivation.