Evaluating the performance of a clinical genome sequencing program for diagnosis of rare genetic disease, seen through the lens of craniosynostosis.

Purpose: Genome sequencing (GS) for diagnosis of rare genetic disease is being introduced into the clinic, but the complexity of the data poses challenges for developing pipelines with high diagnostic sensitivity. We evaluated the performance of the Genomics England 100,000 Genomes Project (100kGP) panel-based pipelines, using craniosynostosis as a test disease.

Methods: GS data from 114 probands with craniosynostosis and their relatives (314 samples), negative on routine genetic testing, were scrutinized by a specialized research team, and diagnoses compared with those made by 100kGP.

Alendronate binds to tooth root surfaces and inhibits progression of feline tooth resorption: a pilot proof-of-concept study.

Tissue distribution, bioavailability, and efficacy of alendronate in preventing progression of resorption of teeth were evaluated in cats. [Butyl-4-14C-]-alendronate accumulates on subgingival tooth and alveolar bone surfaces adjacent to vascularized tissue resulting in concentration of the drug around tooth roots. Three cats were treated with a 0.

Exacerbations of COPD diagnosed in primary care: changes in spirometry and relationship to symptoms.

The study objective was to assess spirometric changes during resolution of acute exacerbations of COPD diagnosed and treated in primary care and their relationship to clinical features. Spirometry was carried out on 101 patients with AECOPD presenting to a primary care physician on the day of presentation, days 5, 10-14, 28, and 56 after presentation and traces were analyzed including quality and reproducibility. Eighty-three patients produced at least one technically acceptable spirometer trace at presentation and 60 patients produced acceptable traces at all time points.

Identification of biomarkers for tumor endothelial cell proliferation through gene expression profiling.

Extensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cells. Inhibition of KDR catalytic activity blocks tumor neoangiogenesis, reduces vascular permeability, and, in animal models, inhibits tumor growth and metastasis.

Flexible transgastric peritoneoscopy: a novel approach to diagnostic and therapeutic interventions in the peritoneal cavity.

Background: A novel endoscopic peroral transgastric approach to the peritoneal cavity was tested in a porcine model in acute and long-term survival experiments.

Methods: Transgastric peritoneoscopy was evaluated in 50-kg pigs. After upper endoscopy, the peritoneal cavity was accessed by needle-knife puncture of the gastric wall, followed by extension of the incision either with a pull-type sphincterotome or by balloon dilation.