Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

ICAR: endoscopic skull‐base surgery

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How Cell Concentrations Are Implicated in Cell Selectivity of Antimicrobial Peptides

Antimicrobial peptides (AMPs) are known to selectively bind to and kill microbes over host cells. Contrary to a conventional view, there is now evidence that AMP’s cell selectivity varies with cell densities and is not uniquely determined. Using a coarse-grained model, we study how the cell selectivity of membrane-lytic AMPs, defined as the ratio between their minimum hemolytic (MHC) and minimum inhibitory concentrations (MIC), depends on cell densities or on the way it is measured. A general picture emerging from our study is that the selectivity better captures peptide’s intrinsic properties at low cell densities. The selectivity, however, decreases and becomes less intrinsic as the cell density increases, as long as it is chosen to be the same for both types of cells. Importantly, our results show that the selectivity can be excessively overestimated if higher host cell concentrations are used; in contrast, it becomes mistakenly small if measured for a mixture of both types of cells, even with similar choices of cell densities (i.e., higher host cell densities). Our approach can be used as a fitting model for relating the intrinsic selectivity to the apparent (cell-density-dependent) one

Heterogeneous absorption of antimicrobial peptide LL37 in escherichia coli cells enhances population survivability

Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative, population and single-cell level experiments with theoretical modeling. We observe an unexpected, rapid absorption and retention of a large number of LL37 peptides by E. coli cells upon the inhibition of their growth, which increases population survivability. This transition occurs more likely in the late stage of cell division cycles. Cultures with high cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising observations, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37 peptides