The Insulin Resistance Intervention after Stroke trial: a perspective on future practice and research

The prevention of recurrent events after ischaemic stroke and transient ischaemic attack is well established and based on lifestyle changes, antithrombotics, statins, antihypertensives and carotid surgery. The international IRIS trial assessed whether pioglitazone, a glucose-lowering insulin-sensitizing drug, would reduce recurrent vascular events in patients with ischaemic stroke or transient ischaemic attack. After 4.8 years, pioglitazone therapy was associated with reduced vascular events and new diabetes, and an increase in weight, oedema and bone fractures. Pioglitazone may add to the strategies for preventing further events in patients with stroke or transient ischaemic attack

Prioritization of Epilepsy Associated Candidate Genes by Convergent Analysis

Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research.In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways.The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases