Titanium based cranial reconstruction using incremental sheet forming

In this paper, we report recent work in cranial plate manufacturing using incremental sheet forming (ISF) process. With a typical cranial shape, the ISF process was used to manufacture the titanium cranial shape by using different ISF tooling solutions with and without backing plates. Detailed evaluation of the ISF process including material deformation and thinning, geometric accuracy and surface finish was conducted by using a combination of experimental testing and Finite Element (FE) simulation. The results show that satisfactory cranial shape can be achieved with sufficient accuracy and surface finish by using a feature based tool path generation method and new ISF tooling design. The results also demonstrate that the ISF based cranial reconstruction has the potential to achieve considerable lead time reduction as compared to conventional methods for cranial plate manufacturing. This outcome indicates that there is a potential for the ISF process to achieve technological advances and economic benefits as well as improvement to quality of life

Functional Rotation of the Transporter AcrB: Insights into Drug Extrusion from Simulations

The tripartite complex AcrAB-TolC is the major efflux system in Escherichia coli. It extrudes a wide spectrum of noxious compounds out of the bacterium, including many antibiotics. Its active part, the homotrimeric transporter AcrB, is responsible for the selective binding of substrates and energy transduction. Based on available crystal structures and biochemical data, the transport of substrates by AcrB has been proposed to take place via a functional rotation, in which each monomer assumes a particular conformation. However, there is no molecular-level description of the conformational changes associated with the rotation and their connection to drug extrusion. To obtain insights thereon, we have performed extensive targeted molecular dynamics simulations mimicking the functional rotation of AcrB containing doxorubicin, one of the two substrates that were co-crystallized so far. The simulations, including almost half a million atoms, have been used to test several hypotheses concerning the structure-dynamics-function relationship of this transporter. Our results indicate that, upon induction of conformational changes, the substrate detaches from the binding pocket and approaches the gate to the central funnel. Furthermore, we provide strong evidence for the proposed peristaltic transport involving a zipper-like closure of the binding pocket, responsible for the displacement of the drug. A concerted opening of the channel between the binding pocket and the gate further favors the displacement of the drug. This microscopically well-funded information allows one to identify the role of specific amino acids during the transitions and to shed light on the functioning of AcrB

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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