Delay in pediatric epilepsy surgery: A caregiver's perspective.

The timing of epilepsy surgery is complex, and there is not a structured pathway to help families decide whether to continue medical management or pursue surgical treatment. We surveyed caregivers of pediatric epilepsy surgery patients. Fifty-eight respondents answered the majority of questions. Thirty caregivers wished their child had undergone epilepsy surgery earlier compared with twenty who felt surgery was done at the appropriate time, and eight were unsure. In retrospect, caregivers who wished their child's surgery had been performed sooner had a significantly longer duration of epilepsy prior to the surgery [44.1±71.7 (months±standard deviation (SD), N=27)], compared with those who felt content with the timing of the surgery [12.8±14.1 (months±SD, N=20), p=0.0034]. Caregivers were willing to accept a lower likelihood of seizure freedom than their physician reported was likely. Most caregivers were willing to accept deficits in all domains surveyed; caregivers had high acceptance of motor deficits, cognitive deficits, behavioral change, and language loss. Future studies are needed to focus on how to improve the education of caregivers and neurologists about the benefits and risks of epilepsy surgery and accelerate the pipeline to epilepsy surgery to improve caregiver satisfaction.

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes.

Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders, and RNA-DNA interactions. These play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific families and subfamilies of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate sustained interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to shaping 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution.