Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration.

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.

Does motivational interviewing have a role in dentistry?

Traditional approaches to health promotion involve clinicians imparting knowledge to patients and 'telling' patients what changes they should make to benefit their health. This so-called 'fixing reflex' can be counterproductive and ineffective, creating unhelpful discord between clinicians and patients. There is little evidence that this approach is wholly effective in bringing about healthier patient behaviours.

A single-centre early experience of the Pulse™ navigation system for posterior spinal fusion in adolescent idiopathic scoliosis (AIS).

Purpose: Pedicle screw-based constructs are the standard of surgical management in AIS. Several manufacturers have developed navigation systems utilising intraoperative 3D imaging to improve screw placement accuracy. However, concerns remain regarding intraoperative radiation exposure utilising these systems compared to traditional techniques.