Size distribution of embryos produced by crystal-rod contacts

We performed contact nucleation experiments on the (010) face of potassium hydrogen phthalate (KAP) crystals growing in a stagnant supersaturated aqueous solution and determined - after a given growth time t - (ex situ) the crystal size distribution (CSD) of the secondary nuclei (which at t = 0 are called "embryos") by using a scanning electron microscope (SEM). The origin of the secondary nuclei could clearly be revealed (damage to the crystal surface). The CSD can be fitted with a log-normal distribution which is typical for many powders obtained by grinding. Minimum size and mean size can be quantitatively understood by elementary fracture mechanics

Long-term oral antibiotic treatment : why, what, when and to whom?

Antibiotics are typically prescribed as short courses for acute infections, in order to reduce bacterial load, shift the balance in favour of host defences and thus help to overcome infection. Over the past decade, however, interest in the long-term anti-inflammatory and immunomodulatory effects of selected antibiotics has been on the increase. Since the clinical effectiveness of erythromycin was reported in diffuse panbronchiolitis in the 1980s, the use of macrolides has been adopted into many other chronic inflammatory airway diseases characterised by frequent exacerbations, including cystic fibrosis (CF), non-CF bronchiectasis, COPD, severe noneosinophilic asthma, bronchiolitis obliterans after lung transplantation and organising pneumonia. In this chapter, we discuss the indications and limitations of long-term macrolide treatment in these chronic respiratory conditions

Histopathology and genetic susceptibility in COVID-19 pneumonia

The clinical features of COVID-19 range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Little is known about the mechanisms behind observed episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. As in other diseases, the answer to some of these questions may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping, which enable mechanistic insights into the differences in pathogenesis and underlying immunological and tissue regenerative response patterns. We will aim to provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease

Spiral surface growth without desorption

Spiral surface growth is well understood in the limit where the step motion is controlled by the local supersaturation of adatoms near the spiral ridge. In epitaxial thin-film growth, however, spirals can form in a step-flow regime where desorption of adatoms is negligible and the ridge dynamics is governed by the non-local diffusion field of adatoms on the whole surface. We investigate this limit numerically using a phase-field formulation of the Burton-Cabrera-Frank model, as well as analytically. Quantitative predictions, which differ strikingly from those of the local limit, are made for the selected step spacing as a function of the deposition flux, as well as for the dependence of the relaxation time to steady-state growth on the screw dislocation density.Comment: 9 pages, 3 figures, RevTe

Circulating Sclerostin Levels Are Decreased in Patients with Endogenous Hypercortisolism and Increase after Treatment

CONTEXT: Increased bone fragility is a frequent complication of hypercortisolism due predominantly to suppression of bone formation. Sclerostin is an osteocyte-produced negative regulator of bone formation, which is up-regulated by glucocorticoids in mice. OBJECTIVE: Our objective was to assess the effect of endogenous hypercortisolism on circulating sclerostin and bone turnover in humans. DESIGN: We measured sclerostin, beta-C-terminal telopeptide, amino-terminal propeptide of type 1 procollagen, and fibroblast growth factor 23 in blood samples of 21 patients with endogenous hypercortisolism and 21 age- and gender-matched controls. In 12 patients, measurements were repeated at various time intervals after successful surgical treatment (transsphenoidal surgery or adrenalectomy). RESULTS: Plasma sclerostin levels were significantly decreased in patients compared with controls (112+/-49 vs. 207+/-48 pg/ml, P<0.001). In the 12 patients who were evaluated after surgical treatment, sclerostin levels increased from 121.4+/-46.5 to 175.8+/-78.5 pg/ml (P=0.003). These changes in plasma sclerostin levels were accompanied by significant increases in levels of fibroblast growth factor 23 (from 44.2+/-12.2 to 84.0+/-58.8 pg/ml, P=0.017) and of the bone turnover markers amino-terminal propeptide of type 1 procollagen (from 31.7+/-18.2 to 94.2+/-92.2 ng/ml, P=0.037) and beta-C-terminal telopeptide (from 134.2+/-44 to 409.2+/-285 pg/ml, P=0.005). CONCLUSIONS: Contrary to the findings in mice, circulating sclerostin is decreased in patients with chronic endogenous hypercortisolism and increases after treatment. These findings suggest that in humans, chronic exposure to glucocorticoids affects the number or function of osteocytes rather than the production of sclerostin

<i>In</i> <i>vitro </i>regulation of fibroblast growth factor 23 by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D synthesized by osteocyte-like MC3T3-E1 cells

Fibroblast growth factor 23 (FGF23) is produced and secreted by osteocytes and is essential for maintaining phosphate homeostasis. One of the main regulators of FGF23, 1,25-dihydroxyvitamin D (1,25(OH)2D3), is primarily synthesized in the kidney from 25-hydroxyvitamin D (25(OH)D) by 1α-hydroxylase (encoded by CYP27B1). Hitherto, it is unclear whether osteocytes can convert 25(OH)D and thereby allow for 1,25(OH)2D3 to induce FGF23 production and secretion locally. Here, we differentiated MC3T3-E1 cells toward osteocyte-like cells expressing and secreting FGF23. Treatment with 10-6 M 25(OH)D resulted in conversion of 25(OH)D to 150 pmol/L 1,25(OH)2D3 and increased FGF23 expression and secretion, but the converted amount of 1,25(OH)2D3 was insufficient to trigger an FGF23 response, so the effect on FGF23 was most likely directly caused by 25(OH)D. Interestingly, combining phosphate with 25(OH)D resulted in a synergistic increase in FGF23 expression and secretion, likely due to activation of additional signaling pathways by phosphate. Blockage of the vitamin D receptor (VDR) only partially abolished the effects of 25(OH)D or 25(OH)D combined with phosphate on Fgf23, while completely inhibiting the upregulation of cytochrome P450 family 24 subfamily A member 1 (Cyp24a1), encoding for 24-hydroxylase. RNA sequencing and in silico analyses showed that this could potentially be mediated by the nuclear receptors Retinoic Acid Receptor β (RARB) and Estrogen Receptor 2 (ESR2). Taken together, we demonstrate that osteocytes are able to convert 25(OH)D to 1,25(OH)2D3, but this is insufficient for FGF23 activation, implicating a direct effect of 25(OH)D in the regulation of FGF23, which occurs at least partially independent from its cognate VDR. Moreover, phosphate and 25(OH)D synergistically increase expression and secretion of FGF23, which warrants investigating consequences in patients receiving a combination of vitamin D analogues and phosphate supplements. These observations help us to further understand the complex relations between phosphate, vitamin D, and FGF23.</p