Plos One
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Sclerostin is a circulating osteocyte-derived glycoprotein that negatively regulates Wnt-signaling after binding the LRP5/LRP6 co-receptors. Pharmacologic sclerostin inhibition produces bone anabolic effects after spinal cord injury (SCI), however, the effects of sclerostin-antibody (Scl-Ab) on muscle morphology remain unknown. In comparison, androgen administration produces bone antiresorptive effects after SCI and some, but not all, studies have reported that testosterone treatment ameliorates skeletal muscle atrophy in this context. ⋯ In comparison, TE partially prevented soleus atrophy and increased levator ani/bulbocavernosus (LABC) mass by 30-40% (p<0.001 vs all groups). The differing myotrophic responsiveness coincided with a 3-fold higher androgen receptor gene expression in LABC versus soleus (p<0.01). This study provides the first direct evidence that Scl-Ab does not prevent soleus muscle atrophy in rodents after SCI and suggests that variable myotrophic responses in rodent muscles after androgen administration are influenced by androgen receptor expression.
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In human chronic kidney disease (CKD) the extent of renal tubulointerstitial fibrosis correlates with progressive loss of renal function. However, fibrosis can so far only be assessed by histology of kidney biopsies. Magnetic resonance imaging (MRI) can provide information about tissue architecture, but its potential to assess fibrosis and inflammation in diseased kidneys remains poorly defined. ⋯ MRI parameters provide a promising approach to quantitatively assess renal fibrosis and inflammation in CKD. Especially T2 relaxation time correlates well with histological features of CKD and is not influenced by paraformaldehyde fixation of kidney samples. Thus, T2 relaxation time might be a candidate parameter for non-invasive assessment of renal fibrosis in human patients.
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Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. ⋯ Interestingly, in bleomycin-administered S1pr2-/- mice, STAT6 phosphorylation in BALF cells was substantially diminished compared with wild-type mice. Finally, pharmacological S1PR2 blockade in S1pr2+/+ mice alleviated bleomycin-induced lung fibrosis. Thus, S1PR2 facilitates lung fibrosis through the mechanisms involving augmentation of IL-13 expression and its signaling in BALF cells, and represents a novel target for treating lung fibrosis.
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Review Meta Analysis Comparative Study
Digoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.
During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. ⋯ PROSPERO CRD42016052935.
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Review Meta Analysis
The predictive value of bedside ultrasound to restore spontaneous circulation in patients with pulseless electrical activity: A systematic review and meta-analysis.
The prognosis of pulseless electrical activity is dismal. However, it is still challengable to decide when to terminate or continue resuscitation efforts. The aim of this study was to determine whether the use of bedside ultrasound (US) could predict the restoration of spontaneous circulation (ROSC) in patients with pulseless electrical activity (PEA) through the identification of cardiac activity. ⋯ In cardiac arrest patients who present with PEA, bedside US has an important role in predicting ROSC. The presence of cardiac activity in PEA patients may encourage more aggressive resuscitation.