Haematophagous organisms are a rich source of salivary anticoagulant polypeptides that exert their activity by blocking the catalytic site and one of two positively charged exosites on the host protease thrombin. Here, we describe a molecular engineering approach to hybridise post-translationally sulfated polypeptides from different blood-feeding organisms to enhance anticoagulant activity. This led to the discovery of a triply sulfated hybrid anticoagulant, XChimera, possessing fragments from flea, leech, and fly salivary polypeptides that exhibits femtomolar inhibitory activity against thrombin. The crystallographic structure of a complex of XChimera with thrombin shows that it displays a trivalent binding mode in which it simultaneously blocks three functional sites of the protease, the active site and exosites I and II. This trivalent chimera exhibited ultrapotent anticoagulant activity in a suite of in vitro clotting assays and was also shown to possess potent in vivo antithrombotic activity in a murine model of thrombosis.

Background/Objectives: There is a lack of both guidelines and evidence supporting the non-surgical treatment of juvenile idiopathic scoliosis (JIS). We present a case series of four juveniles presenting with primary right-thoracic curve types who were treated with the ScoliBrace^®. Methods: Four patients with JIS from a single scoliosis clinic database who met predefined inclusion and exclusion criteria were included in this case series. All patients were braced with the ScoliBrace^®, a three-dimensional rigid brace designed to target the deformity using Mirror Image^® postural over-correction. All patients were initially prescribed full-time (23 h/day) bracing; three patients later transitioned to part-time wear. Cobb angle and angle of trunk rotation (ATR) measures were monitored at 90-day intervals after a one-month in-brace check. Results: Patients had a mean (± standard deviation) initial age of 7.2 ± 1.5 years and were followed for a mean of 8.8 ± 1.7 years, including 22.5 ± 15.2 months of post-weaning monitoring. At final follow-up, the primary thoracic curve Cobb angle was improved by a mean of 21.5 ± 12.6°, and ATR by 7.5 ± 2.9°. Conclusions: The ScoliBrace^® brace and management protocol was associated with an average 21.5° Cobb angle reduction in primary right-thoracic scoliosis curves in four juvenile patients with idiopathic scoliosis. Given the small, uncontrolled sample, these findings should be interpreted as preliminary; they support further evaluation of the ScoliBrace^® in larger, prospective controlled studies.