👤 Hannah L R Kendall

Transcutaneous closure of patent ductus arteriosus (PDA) in childhood is a common procedure. Long-term follow-up by paediatric cardiologists is variable. Identification and classification of postoperative complications may enable targeted follow-up and timelier discharges. This study aimed to characterize complication rates and assess discharge timing. This is a single-centre retrospective study of paediatric patients (aged 0-15 years) who underwent a transcutaneous closure of a PDA between January 2006 and December 2015. A total of 156 patients who underwent interventional occlusion of a PDA were included. Complications were seen in 18 of 156 (12%) patients. High-grade complications occurred in 8 of 156 (5.1%) patients; these included device embolization, failure requiring surgical closure, or repeated interventional closure. Moderate to low-grade complications including flow acceleration in the aorta and left pulmonary artery (LPA) occurred in 10 of 156 (6.4%) patients. Fourteen of 18 (77%) complications were immediately apparent. Late mild to moderate obstruction of the descending aorta or LPA occurred in 3 of 156 (2%) patients. Later obstruction occurred in the Amplatzer ductal occluder 1 (ADO1) group only with large (4.5-5 mm) ducts. The average follow-up time for all patients was 81 (±47) months. Younger age at insertion and larger size of ADO1 devices were associated with later obstruction. In our cohort, PDA occlusion was associated with a 5.1% major complication rate, which is evident within 24 hours; a further 2% (all treated with ADO1 devices) developed between mild and moderate aortic or LPA obstruction at least 1 year after the procedure. To date, this has not required intervention. It may therefore be prudent to continue longer-term surveillance of patients who have undergone PDA occlusion with the ADO1 device. Show less

Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of Show less

The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, the mechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease. Previously, our group developed methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that human iPSCs can be differentiated into prostate organoids using neonatal rat seminal vesicle mesenchyme in vitro. The organoids can be used to study prostate development or modified to study prostate cancer. We also elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus and neonatal seminal vesicles. We identified candidate drivers of prostate development evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2 and Lrp4. This work lays the foundations for further interrogation of the reactivation of developmental genes in adulthood, leading to prostate disease. Show less