Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) and other neurodegenerative diseases (NDs) cause substantial health-related and economic burdens, but progress towards preventative or ameliorative treatments has been limited. Genome-wide association studies have identified hundreds of risk loci containing single nucleotide polymorphisms (SNPs) that alter risk for these diseases, but >90% of these SNPs are in noncoding regions, which are cell type-specific and difficult to study. To address this gap, we have characterized the epigenomes of iPSC-derived neuronal and glial cells and performed CRISPRi single cell screening to dissect the molecular and cellular mechanisms underlying 10 ND risk loci.

Myocardial ischaemia following COVID-19: a cardiovascular magnetic resonance study.

The pathophysiology of myocardial injury following COVID-19 remains uncertain. COVID-HEART was a prospective, multicentre study utilising cardiovascular magnetic resonance (CMR) to characterise COVID-related myocardial injury. In this pre-specified analysis, the objectives were to examine (1) the frequency of myocardial ischaemia following COVID-19, and (2) the association between ischaemia and myocardial injury.

Imaging pathology in archived cornea with Fuchs' endothelial corneal dystrophy including tissue reprocessing for volume electron microscopy.

Fuchs' endothelial corneal dystrophy (FECD) is a common sight-threatening condition characterised by pathological changes in the posterior cornea. Here we report observations by light, transmission and volume scanning electron microscopy on changes in the endothelium and matrix associated with the characteristic deformations of Descemet's membrane, termed guttae. Specimens were archived full-thickness human corneal tissue, removed during graft surgery, that had been fixed, stained and embedded by conventional processing methods for examination by transmission electron microscopy more than 40-years previously.

Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.

Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET).

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence.