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We investigated the diagnostic utility of combined nerve and vascular ultrasound in thoracic outlet syndrome (TOS) in a retrospective cohort study on two sites, involving 167 consecutive patients with the clinical symptoms suggestive of neurogenic and/or vascular TOS, and an age- and sex-matched control group. All patients and control subjects underwent nerve ultrasound of the supraclavicular brachial plexus to look for fibromuscular anomalies / compression of the brachial plexus in the scalenic region, and vascular ultrasound of the infraclavicular subclavian artery with the arm in neutral and abducted position, serving as an indicator for costoclavicular compression of the neurovascular bundle. Based on clinical symptoms, neurogenic TOS (81%) was the most frequent type of TOS, followed by combined neurogenic and arterial TOS (8%). The frequency of abnormal nerve and/or vascular ultrasound findings differed significantly from the control group (P<0.00001). The pooled sensitivity was 48% for nerve ultrasound, 85% for vascular ultrasound, and 94% when combined. Among the findings, the fibromuscular 'wedge-sickle sign', indicating compression of the lower trunk in the scalenic region by a congenital fibromuscular anomaly (e.g. Roos ligaments), showed the highest specificity (100%). A bony 'wedge-sickle sign' was also delineated, where lower trunk compression is caused by the neck of the 1st rib. As implied by the higher sensitivity of vascular ultrasound, the most common site of compression was the costoclavicular space, but multilevel compression was also frequently observed. In summary, combined nerve and vascular ultrasound is a sensitive and reliable method to support the diagnosis of TOS. It can also identify the site(s) of compression, with obvious therapeutic consequences. [ABSTRACT FROM AUTHOR]

Lipases are essential and widely used biocatalysts. Hence, the production of lipases requires a detailed understanding of the molecular mechanism of its folding and secretion. Lipase A from Pseudomonas aeruginosa, PaLipA, constitutes a prominent example that has additional relevance because of its role as a virulence factor in many diseases. PaLipA requires the assistance of a membrane‐integrated steric chaperone, the lipase‐specific foldase Lif, to achieve its enzymatically active state. However, the molecular mechanism of how Lif activates its cognate lipase has remained elusive. Here, we show by molecular dynamics simulations at the atomistic level and potential of mean force computations that Lif catalyzes the activation process of PaLipA by structurally stabilizing an intermediate PaLipA conformation, particularly a β‐sheet in the region of residues 17–30, such that the opening of PaLipA's lid domain is facilitated. This opening allows substrate access to PaLipA's catalytic site. A surprising and so far not fully understood aspect of our study is that the open state of PaLipA is unstable compared to the closed one according to our computational and in vitro biochemical results. We thus speculate that further interactions of PaLipA with the Xcp secretion machinery and/or components of the extracellular matrix contribute to the remaining activity of secreted PaLipA. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]