Plos One
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Vascular smooth muscle cells from the pulmonary arteries (HPASMC) of subjects with pulmonary arterial hypertension (PAH) exhibit hyperplastic growth. The PAH HPASMC display an increased sensitivity to fetal bovine serum (FBS) and undergo growth at a very low, 0.2%, FBS concentration. On the other hand, normal HPASMC (obtained from non-PAH donors) do not proliferate at low FBS (0.2%). ⋯ Furthermore, the knockdown of PLK1 expression lowers the protein level of FOXM1. On the other hand, inhibiting the action of FOXO1, a growth inhibitor, further increases the expression of FOXM1 in PAH HPASMC. Although PLK1 and FOXM1 clearly participate in PAH HPASMC hyperplasia, at this time it is not clear whether their increased activity is the primary driver of the hyperplastic behavior of the PAH HPASMC or merely a component of the pathway(s) leading to this response.
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The clinical course of chronic hypersensitivity pneumonitis (HP) with fibrosis is similar to that of idiopathic pulmonary fibrosis (IPF). Current research is expected to identify biomarkers effective in predicting the deterioration of lung function in a clinical setting. Our group analyzed the relationships between the following parameters in chronic bird-related HP: patient characteristics, serum markers, lung function, HRCT findings, BALF profiles, and the worsening of lung function. ⋯ Serum levels of CXCL9 and CCL17 were significant variables in a multivariate logistic regression analysis of factors associated with VC decline. Patients with a chemokine profile combining lower serum CXCL9 and higher serum CCL17 exhibited significantly larger VC decline in a cluster analysis. Higher serum CCL17 and lower serum CXCL9 were important predictors of worsening lung function in patients with chronic bird-related HP.
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Opioid prescriptions for chronic pain and subsequent opioid-related complications have risen dramatically in the US. Recent data suggest that medical marijuana laws have been associated with lower state-level opioid overdose mortality. In a national survey, we examined the prevalence of substitution of marijuana for opioids among US adults taking opioids for pain. ⋯ Among the 5% (n = 486) who reported ever using marijuana and using opioids in the past year, 43% used opioids daily, and 23% reported current (past 30 day) marijuana use. Forty-one percent reported a decrease or cessation of opioid use due to marijuana use; 46% reported no change in opioid use; and 8% reported an increase in opioid use. We found that a substantial number of US adults reported that they substituted marijuana for opioids.
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The corpus callosum (CC) is the biggest commissure that links cerebral hemispheres. Guidepost structures develop in the cortical midline during CC development and express axon guidance molecules that instruct neurons regarding the proper direction of axonal elongation toward and across the cortical midline. Neuropilin-1 (Npn1), a high affinity receptor for class 3 semaphorins (Sema3s) localized on cingulate pioneering axons, plays a crucial role in axon guidance to the midline through interactions with Sema3s. ⋯ To further examine the role of PlexinA1 in CC development, the CC phenotype was examined in PlexinA1 KO mice at postnatal day 0.5 (P0.5). Most of the PlexinA1 KO mice at P0.5 showed agenesis of the CC. These results indicate the crucial involvement of PlexinA1 in the midline crossing of callosal axons during CC development in BALB/cAJ mice.
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Critically-ill surgical patients are at higher risk for sarcopenia, which is associated with worse survival. Sarcopenia may impair the respiratory musculature, which can subsequently influence the outcome of ventilator weaning. Although there are a variety of weaning parameters predictive of weaning outcomes, none have tried to incorporate "muscle strength" or "sarcopenia". The aim of the current study was to explore the association between sarcopenia and difficult-to-wean (DtW) in critically-ill surgical patients. The influence of sarcopenia on ICU mortality was also analyzed. ⋯ Sarcopenia is an independent risk factor for DtW and ICU mortality. TPA has predictive value when assessing weaning outcomes and can be used as an effective adjunct predictor along with conventional weaning parameters.