Sex-Based Differences in Endovascular Thrombectomy Outcomes for Large Ischemic Stroke: A SELECT2 Subanalysis.

Background: Several social and biological factors are shown to differentially affect stroke outcomes between men and women. We evaluated whether clinical outcomes and endovascular thrombectomy (EVT) treatment effects differed between the sexes in patients presenting with large ischemic stroke.

Methods: The SELECT2 trial (A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke) was a randomized controlled trial assessing the efficacy and safety of EVT in patients with large strokes across the United States, Canada, Europe, Australia, and New Zealand between October 2019 and September 2022.

Early antibiotic exposure and risk of psychiatric and neurocognitive outcomes: systematic review and meta-analysis.

Background: The prenatal and early-life periods pose a crucial neurodevelopmental window whereby disruptions to the intestinal microbiota and the developing brain may have adverse impacts. As antibiotics affect the human intestinal microbiome, it follows that early-life antibiotic exposure may be associated with later-life psychiatric or neurocognitive outcomes.

Aims: To explore the association between early-life (in utero and early childhood (age 0-2 years)) antibiotic exposure and the subsequent risk of psychiatric and neurocognitive outcomes.

IUPHAR Review on muscarinic M1 and M4 receptors as drug treatment targets relevant to the molecular pathology of schizophrenia.

Cobenfy, a co-formulation of xanomeline and trospium, is the first drug not acting on the dopaminergic system of the CNS approved for the treatment of schizophrenia by the FDA. Xanomeline is a muscarinic M1 and M4 receptor (CHRM1 and CHRM4) agonist whilst trospium is a peripherally active CHRM antagonist that reduces the unwanted peripheral side-effects of xanomeline. Relevant to this exciting development, this review details the human CNS cholinergic systems and how those systems are affected by the molecular pathology of schizophrenia in a way suggesting activating the CHRM1 and 4 would be beneficial in treating the disorder.

Two thirds of patients may not need routine 12-month specialist review in an epilepsy clinic: A cross-sectional study of clinic appointments.

Objectives: Timely access to specialist outpatient clinics can be difficult to achieve as outpatient services are often oversubscribed leading to unacceptable wait times. New patients, or those with emergent issues may wait for appointments whilst existing patients are booked in for routine reviews "just in case" there is a problem, using considerable clinic resources. We investigated routine 12-month review appointments to assess whether these appointments changed patient management.

Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.

An iPSC line (FINi003-A) from a male with late-onset developmental and epileptic encephalopathy caused by a heterozygous p.E1211K variant in the SCN2A gene encoding the voltage-gated sodium channel Na1.2.

Many developmental and epileptic encephalopathies (DEEs) result from variants in cation channel genes. Using mRNA transfection, we generated and characterised an induced pluripotent stem cell (iPSC) line from the fibroblasts of a male late-onset DEE patient carrying a heterozygous missense variant (E1211K) in Na1.2(SCN2A) protein.

Common changes in rat cortical gene expression after antidepressant drug treatment: Impacts on metabolism of polyamines, mRNA splicing, regulation of RAS by GAPs, neddylation and GPCR ligand binding.

Objectives: This study sought to identify pathways affected by rat cortical RNA that were changed after treatment with fluoxetine or imipramine.

Methods: We measured levels of cortical RNA in male rats using GeneChip Rat Exon 1.0 ST Array after treatment with vehicle (0.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

Background: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients.

Methods: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand.

Network-based drug repurposing for schizophrenia.

Despite recent progress, the challenges in drug discovery for schizophrenia persist. However, computational drug repurposing has gained popularity as it leverages the wealth of expanding biomedical databases. Network analyses provide a comprehensive understanding of transcription factor (TF) regulatory effects through gene regulatory networks, which capture the interactions between TFs and target genes by integrating various lines of evidence.

Some key parameters in contextual fear conditioning and extinction in adult rats.

Contextual fear conditioning is a behavioral paradigm used to assess hippocampal-dependent memory in experimental animals. Perception of the context depends on activation of a distinct population of neurons in the hippocampus and in hippocampal-related areas that process discrete aspects of context perception. In the absence of any putatively associated cue, the context becomes the salient element that may warn of an upcoming aversive event; and in particular conditions, animals generalize this warning to any new or similar context.

Use of gene regulatory network analysis to repurpose drugs to treat bipolar disorder.

Background: Bipolar disorder (BD) presents significant challenges in drug discovery, necessitating alternative approaches. Drug repurposing, leveraging computational techniques and expanding biomedical data, holds promise for identifying novel treatment strategies.

Methods: This study utilized gene regulatory networks (GRNs) to identify significant regulatory changes in BD, using network-based signatures for drug repurposing.

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models.

A great deal of nanocarriers have been applied to induce ferroptosis in cancer research, yet there are limited examples of nanocarrier formulations to rescue ferroptosis, which can be applied to neurodegeneration, inflammation, liver damage, kidney disease, and more. Here, we present the synthesis, characterization, and in vitro evaluation of pH-responsive, core-cross-linked micelle (CCM) ferrostatin-1 (Fer-1) conjugates with amine, valproic acid, and biotin surface chemistries. Fer-1 release from stable and defined CCM Fer-1 conjugates was quantified, highlighting the sustained release for 24 h.

Self-management strategies for people with epilepsy: An overview of reviews.

Objective: This overview of systematic reviews aimed to appraise evidence regarding self-management strategies on health-related quality of life, self-efficacy, medication compliance, seizure status and psychosocial outcomes compared to usual care for people with epilepsy.

Methods: Databases were searched until September 2022 using MeSH terms included OVID Medline, Embase and Cochrane. Following application of eligibility criteria, data were extracted and quality of articles was assessed using the AMSTAR2 checklist.

Navigating the multiple dimensions of the creativity-mental disorder link: a Convergence Mental Health perspective.

Background: This paper discusses a paradox in mental health. It manifests as a relationship between adverse "bad" effects (suffering, clinical costs, loss of productivity) in individuals and populations and advantageous "good" aspects of mental disorders. These beneficial aspects (scientific, artistic and political accomplishments) emanate at the societal level through the frequently unprecedented creativity of people suffering from mental disorders and their relatives.

Generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene.

The most common cause of autosomal recessive familial Parkinson's disease (PD) are mutations in the PRKN/PARK2 gene encoding an E3 ubiquitin protein-ligase PARKIN. We report the generation of an iPSC cell line from the fibroblasts of a male PD patient carrying a common missense variant in exon 7 (p.Arg275Trp), and a 133 kb deletion encompassing exon 8, using transiently-present Sendai virus.

Life-Course Brain Health as a Determinant of Late-Life Mental Health: American Association for Geriatric Psychiatry Expert Panel Recommendations.

This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities.

Common changes in rat cortical gene expression after valproate or lithium treatment particularly affect pre- and post-synaptic pathways that regulate four neurotransmitters systems.

Objectives: We have postulated that common changes in gene expression after treatment with different therapeutic classes of psychotropic drugs contribute to their common therapeutic mechanisms of action.

Methods: To test this hypothesis, we measured levels of cortical coding and non-coding RNA using GeneChip Rat Exon 1.0 ST Array after treatment with vehicle (chow only), chow containing 1.

An innovative model of access and triage to reduce waiting in an outpatient epilepsy clinic: an intervention study.

Background: Delayed access to outpatient care may negatively impact on health outcomes. We aimed to evaluate implementation of the Specific Timely Appointments for Triage (STAT) model of access in an epilepsy clinic to reduce a long waitlist and waiting time.

Methods: This study is an intervention study using pre-post comparison and an interrupted time series analysis to measure the effect of implementation of the STAT model to an epilepsy clinic.

Generation of an iPSC line (FINi001-A) from a girl with developmental and epileptic encephalopathy due to a heterozygous gain-of-function p.R1882Q variant in the voltage-gated sodium channel Na1.2 protein encoded by the SCN2A gene.

A range of epilepsies, including the most severe group of developmental and epileptic encephalopathies (DEEs), are caused by gain-of-function variants in voltage-gated channels. Here we report the generation and characterisation of an iPSC cell line from the fibroblasts of a girl with early infantile DEE carrying heterozygous missense gain-of-function mutation (R1882Q) in Na1.2(SCN2A) protein, using transient transfection with a single mRNA molecule.

A Novel Method to Estimate Levels of Receptors Using an Allosteric Modulator: Focus on Muscarinic M1 Receptor.

This chapter outlines some of the general principles that need to be considered when developing a radioligand binding assay to measure the affinity and density of radioligand binding to a receptor in tissue or on cells. In addition it describes an innovative step forward in using radioligand binding assays to measure levels of muscarinic M1 receptors in human postmortem CNS, using both membrane binding and in situ radioligand binding. These examples show how, using receptor-specific allosteric modulators, it is possible to gain an estimate of the density of a single receptor using a radioligand that is not totally specific to the target site of interest.

Anxiety disorders are associated with reduced bone mineral density in men: Findings from the Geelong Osteoporosis Study.

Objective: Certain psychiatric disorders, including depression, appear to impact adversely on bone health. Anxiety disorders are highly prevalent but few studies have examined their effects on bone tissue. This study investigated the effect of anxiety disorders on bone mineral density (BMD).