Plos One
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Skeletal muscle wasting in acute lung injury (ALI) patients increases the morbidity and mortality associated with this critical illness. The contribution of laryngeal muscle wasting to these outcomes is unknown, though voice impairments and aspiration are common in intensive care unit (ICU) survivors. We evaluated the intrinsic laryngeal abductor (PCA, posterior cricoarytenoid), adductor (CT, cricothyroid) and limb (EDL, extensor digitorum longus) muscles in a mouse model of ALI. ⋯ The vocal cord abductor (PCA) contains a large proportion of fibers expressing MyHC-EO and is spared from muscle atrophy in ALI mice. The lack of MuRF1 expression in the PCA suggests a previously unrecognized mechanism whereby this muscle is spared from atrophy. Atrophy of the vocal cord adductor (CT) may contribute to the impaired voice and increased aspiration observed in ICU survivors. Further evaluation of the sparing of muscles involved in systemic wasting diseases may lead to potential therapeutic targets for these illnesses.
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Accurate, continuous, left ventricular stroke volume (SV) measurements can convey large amounts of information about patient hemodynamic status and response to therapy. However, direct measurements are highly invasive in clinical practice, and current procedures for estimating SV require specialized devices and significant approximation. ⋯ The method presented demonstrates that the magnitude and trends of SV can be accurately estimated from pressure waveforms alone, without the need for identification of complex physiological metrics where strength of correlations may vary significantly from patient to patient.
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Hyperactive mammalian target of rapamycin (mTOR) is associated with cognitive deficits in several neurological disorders including tuberous sclerosis complex (TSC). The phosphorylation of the mRNA-binding protein FMRP reportedly depends on mTOR complex 1 (mTORC1) activity via p70 S6 kinase 1 (S6K1). Because this phosphorylation is thought to regulate the translation of messages important for synaptic plasticity, we explored whether FMRP phosphorylation of the S6K1-dependent residue (S499) is altered in TSC and states of dysregulated TSC-mTORC1 signaling. ⋯ Neither up- nor down-regulation of the mTORC1-S6K1 axis in vivo or in vitro had any effect on phospho-FMRP S499 levels. In addition, FMRP S499 phosphorylation was unaltered in S6K1-knockout mice. Collectively, these data strongly suggest that FMRP S499 phosphorylation is independent of mTORC1-S6K1 activity and is not altered in TSC.
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In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered rheological behavior of mucus results in chronic lung infection and inflammation, which causes most of the cases of morbidity and mortality, although the cystic fibrosis complications affect other organs as well. ⋯ In particular, a new diagnostic parameter based on the correlation between CF sputum viscoelastic properties and the severity of the disease, expressed in terms of FEV1 and bacterial colonization, was developed. By using principal component analysis, we show that the types of colonization and FEV1 classes are significantly correlated to the elastic modulus, and that the latter can be used for CF severity classification with a high predictive efficiency (88%). The data presented here show that the elastic modulus of airways mucus, given the high predictive efficiency, could be used as a new clinical parameter in the prognostic evaluation of cystic fibrosis.
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DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. ⋯ Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.