The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

A survey of the workload generated by older surgical patients referred to on-call medical registrars—SNAP-3

BackgroundOlder surgical patients who develop medical problems are commonly referred to medical teams, which can be proactive physician-led teams or through reactive referral to the on-call medical registrar.MethodsA cross-sectional survey of on-call medical registrars who received referrals from surgical teams was conducted in March–June 2022 at 140 NHS hospitals. It focused on the workload derived from referrals of older surgical patients to on-call medical registrars, excluding referrals to existing services such as perioperative medicine, orthogeriatric, or medical specialty teams. To minimise recall bias, completion of the survey was encouraged regardless of whether a registrar had received a referral. The aim of this survey was to estimate the unplanned, acute workload generated by older surgical patients requiring referral to on-call medical registrars. The survey also aimed to estimate the prevalence and nature of training in perioperative medicine amongst medical registrars.ResultsDuring an on-call shift, 41.3% (266/644) of medical registrars received at least one referral regarding an older surgical patient. The commonest indications were arrhythmia, acute respiratory problems, electrolyte abnormalities, suspected myocardial infarction, sepsis, and delirium. Three-quarters of registrars reported not receiving training in perioperative management of older patients.ConclusionsThe findings highlight the significant workload and training gaps faced by medical registrars in managing older surgical patients. Bridging the gap between national recommendations and local services may reduce demands on on-call registrars and improve care

Abstract 11: Asymmetric division via nonrandom chromosomal cosegregation potentially defines a novel class of universal cancer stem cells

Abstract Cancer stem cells (CSC) are thought to be responsible for cancer initiation, maintenance, and therapeutic failure. A hallmark of stem cells is self-renewal via asymmetric cell division (ACD) into daughter stem cells and cells predestined for differentiation. In addition, recent reports questioned the ability of the gold standard for testing CSC (xenotransplantation into immunodeficient mice) to truly detect and test CSC. The aim of this study was to demonstrate fundamental stem cell's traits such as ACD with non-random-chromosomal cosegregation (ACD-NRCC) in cancers. Here, we show that a unique self-renewal mechanism i.e. ACD-NRCC occurs in various human cancers using DNA double labeling and confocal microscopy. ACD-NRCC was found exclusively in a subpopulation of CSC (side population and CD133+ cells) and not in the non-cancer-stem-cells fractions. Cells that demonstrated ACD-NRCC also exhibited superior tumor initiation capacity in nude mice (p=0.028). Furthermore, we found that the niche provided by the non-stem cancer cells directly regulates self-renewal via ACD-NRCC. This regulation is dependent on a potentially novel heat sensitive soluble factor (Self Renewal Factor, SRF). Gene expression microarray data showed down-regulation of genes associated with ACD in tested cancers. Detection of ACD-NRCC in various human cancers provides direct evidence for the existence of cancer cells with unique stem cells traits. This is the first report to demonstrate the fundamental stem cells trait of ACD-NRCC in human cancer. Detection of cells capable of undergoing ACD-NRCC in various cancers potentially defines a novel class of CSC with superior tumor initiating capacity. Using ACD-NRCC, we propose a universal method for testing, isolating and targeting CSC. The gene expression microarray data suggested that faulty mechanisms of ACD-NRCC might result in stem cells derived cancers. Further purification of the niche's self-renewal-signals and utilizing our methodology for isolation of CSC have far reaching implications in regenerative medicine, cancer genetics and potential novel cancer therapeutics targeting CSC via ACD-NRCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 11.</jats:p