Surgery impairs glymphatic activity and cognitive function in aged mice.

Delirium is a common complication in elderly surgical patients and is associated with an increased risk of dementia. Although advanced age is a major risk factor, the mechanisms underlying postoperative delirium remain poorly understood. The glymphatic system, a brain-wide network of perivascular pathways, facilitates cerebrospinal fluid (CSF) flow and supports the clearance of metabolic waste.

Clinical and molecular characteristics and long-term outcomes of pediatric intracranial meningiomas: a comprehensive analysis from a single neurosurgical center.

Background: Meningioma represents the most common intracranial tumor in adults. However, it is rare in pediatric patients. We aimed to demonstrate the clinicopathological characteristics and long-term outcome of pediatric meningiomas (PMs).

Effect of Target-Mediated Disposition on Iptacopan Clinical Pharmacokinetics in Participants with Normal or Impaired Hepatic Function.

Iptacopan, a first-in-class complement factor B inhibitor acting proximally in the alternative complement pathway, has been shown to be safe and effective for patients with complement-mediated diseases. Iptacopan selectively binds with high affinity to factor B, a soluble, plasma-based, hepatically produced protein. Factor B is abundant in the circulation but can be saturated at the iptacopan clinical dose of 200 mg twice daily.

Referral for Diabetes Self-Management Education and Support in Adult Primary Care: An Integrative Review.

Aims: The purpose of this integrative review was to identify effective diabetes self-management education and support for increasing adult primary care referrals, participation rates and improving health outcomes for persons with diabetes.

Design: Integrative review.

Methods: A systematic literature search of PubMed/MEDLINE, Embase and CINAHL was performed by applying the PRISMA guidelines.

Uniform volumetric single-cell processing for organ-scale molecular phenotyping.

Extending single-cell analysis to intact tissues while maintaining organ-scale spatial information poses a major challenge due to unequal chemical processing of densely packed cells. Here we introduce Continuous Redispersion of Volumetric Equilibrium (CuRVE) in nanoporous matrices, a framework to address this challenge. CuRVE ensures uniform processing of all cells in organ-scale tissues by perpetually maintaining dynamic equilibrium of the tissue's gradually shifting chemical environment.

TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states.

Mutations in cancer risk genes increase susceptibility, but not all carriers develop cancer. Indeed, while DNA mutations are necessary drivers of cancer, only a small subset of mutated cells go on to cause the disease. To date, the mechanisms underlying individual cancer susceptibility remain unclear.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches.

A guide to the biogenesis and functions of endogenous small non-coding RNAs in animals.

Small non-coding RNAs can be categorized into two main classes: structural RNAs and regulatory RNAs. Structural RNAs, which are abundant and ubiquitously expressed, have essential roles in the maturation of pre-mRNAs, modification of rRNAs and the translation of coding transcripts. By contrast, regulatory RNAs are often expressed in a developmental-specific, tissue-specific or cell-type-specific manner and exert precise control over gene expression.

Accuracy of GFAP and UCH-L1 in predicting brain abnormalities on CT scans after mild traumatic brain injury: a systematic review and meta-analysis.

Purpose: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In recent years, blood biomarkers including glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have shown a promising ability to detect head CT abnormalities following TBI. This review aims to combine the existing research on GFAP and UCH-L1 biomarkers and examine how well they can predict abnormal CT results after mild TBI.

Prevalence, incidence, and complications of malnutrition in severely injured patients.

Background: Severely injured patients may suffer from acute disease-related or injury-related malnutrition involving a marked inflammatory response. This study investigated the prevalence and incidence of malnutrition and its relation with complications in severely injured patients admitted to the intensive care unit (ICU).

Methods: This observational prospective cohort study included severely injured patients (Injury Severity Score ≥ 16), admitted to the ICU of five level-1 trauma centers in the Netherlands and United States.

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.

Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma.

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.

Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian pyridoxal 5'-phosphate-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial pyridoxal 5'-phosphate levels in mammals remains unknown.

Using artificial intelligence to optimize anti-seizure treatment and EEG-guided decisions in severe brain injury.

Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit.

Tenzing Assisted Delivery of Aspiration (TADA) technique for thrombectomy of medium vessel occlusions using the Freeclimb 54 catheter: multicenter experience.

Background: Medium vessel occlusions (MeVOs) account for 25-40% of acute ischemic stroke. The Tenzing 5 (Route 92 Medical, San Mateo, California, USA) and FreeClimb 54 (Route 92 Medical, San Mateo, California, USA) catheter is a novel delivery-aspiration catheter combination designed to facilitate aspiration thrombectomy (AT) of MeVOs. We report our clinical experience using the Tenzing assisted delivery of aspiration (TADA) technique with FreeClimb 54 for first-line AT of MeVO.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

Gut microbiomes are largely unchanged when exposed to their amphibian host's latitudinally variable upper thermal limit.

Climate change will increase the frequency and severity of temperature extremes. Links between host thermal physiology and their gut microbiota suggest that organisms' responses to future climates may be mediated by their microbiomes, raising the question of how the thermal environment influences the microbiome itself. Vertebrate gut microbiomes influence the physiological plasticity of their hosts via effects on immunity, metabolism, and nutrient uptake.

US children from non-English-speaking households are less likely to undergo vision testing.

Purpose: To investigate the association between primary household language and vision testing among children living in the United States from 2016 to 2020.

Methods: This analysis used data for children aged 3-17 years from the National Survey of Children's Health (NSCH), combining survey responses from 2016 to 2020. Primary household language and whether vision testing occurred were determined by survey responses.

The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.

Objective: To compare the efficacy and safety of CMIs mavacamten and aficamten vs.

Regulation of PD-L1 glycosylation and advances in cancer immunotherapy.

Protein glycosylation plays a versatile role in regulating homeostasis, such as cell migration, protein sorting, and the immune response. Drugs aimed at targeting glycosylation have strong implications for immunity enhancement, diagnosis, and cancer regression. Programmed death-ligand 1 (PD-L1), expressed in cancer or antigen-presenting cells, binds to programmed cell death protein 1 (PD-1) and suppresses T cells.

Long term outcomes post-ICD in Chagas cardiomyopathy and non-ischemic cardiomyopathy: A comparative analysis.

Background: Chagas cardiomyopathy (CCM) is a significant cause of ventricular arrhythmias and sudden cardiac death (SCD). Although, implantable cardiac defibrillators (ICD) have been used for all forms of non-ischemic cardiomyopathy (NICM), studies on ICD efficacy in CCM are scarce.

Objective: The present study aims to compare the long-term outcomes, mortality rates, and the occurrence of tachycardia therapies after ICD implantation in patients with CCM and NICM.