Plos One
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Early mobilization can be performed in critically ill patients and improves outcomes. A daily cycling exercise started from day 5 after ICU admission is feasible and can enhance functional capacity after hospital discharge. In the present study we verified the physiological changes and safety of an earlier cycling intervention (< 72 hrs of mechanical ventilation) in critical ill patients. ⋯ In our study, this very early passive cycling exercise in sedated, critically ill, mechanically ventilated patients was considered safe and was not associated with significant alterations in hemodynamic, respiratory or metabolic variables even in those requiring vasoactive agents.
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Autophagy refers to the catabolic process in eukaryotic cells that delivers cytoplasmic material to lysosomes for degradation. This highly conserved process is involved in the clearance of long-lived proteins and damaged organelles. Consequently, autophagy is important in providing nutrients to maintain cellular function under starvation, maintaining cellular homeostasis, and promoting cell survival under certain conditions. ⋯ Interestingly, upregulation of genes containing antioxidant response elements, e.g. glutathione S transferase and NAD(P)H dehydrogenase quinone 1 was observed, suggesting activation of Nrf2 transcription factor. These gene expression changes could be related to an increase in SQSTM1/p62 resulting from autophagy deficiency. In summary, our data indicate that lysosomal accumulation due to the basic lipophilic nature of xenobiotics could be a general mechanism contributing to the perturbation of the autophagy process.
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To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion. ⋯ An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.
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Mitochondrial transcription factor A (TFAM) is normally bound to and remains associated with mitochondrial DNA (mtDNA) when released from damaged cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched DNA), amplifies TNFα release from TLR9-expressing plasmacytoid dendritic cells (pDCs) by engaging RAGE. ⋯ TFAM promoted TNFα release in a splenocyte culture model representing complex cell-cell interactions in vivo with pDCs playing a critical role. To our knowledge, this study is the first to incriminate ECE-1-dependent endosomal cleavage of TLR9 as a critical step in the signaling pathway leading to TNFα release. These findings, and others reported herein, significantly advance our understanding of sterile immune responses triggered by mitochondrial danger signals.
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Previous cohort studies have shown that persons with Alzheimer's disease (AD) have a higher risk of hip fractures but recent data from large representative cohorts is scarce. ⋯ Findings from our nationwide study are in line with previous studies showing that persons with AD, regardless of sex or age, have higher risk of hip fracture in comparison to general population. Although there was some suggestion of effect modification by age or sex, AD was consistently associated with doubling of the risk of incident hip fracture.