Pharmacokinetics of Oral Cannabinoid Δ8-Tetrahydrocannabivarin and Its Main Metabolites in Healthy Participants.

Background: Tetrahydrocannabivarin (THCV) is a phytocannabinoid commonly found in cannabis with potential pharmacological properties; however, its post-acute pharmacokinetics (PK) in humans have not been studied yet. THCV has two isomers, Δ9- and Δ8-THCV, which seem to have different pharmacological properties. We investigated the PK of the Δ8-THCV isomer after oral administration as part of a two-phase, dose-ranging, placebo-controlled trial in healthy participants.

DEAD/H Box 5 (DDX5) Augments E2F1-Induced Cell Death Independent of the Tumor Suppressor p53.

In almost all cancers, the p53 pathway is disabled and cancer cells survive. Hence, it is crucially important to induce cell death independent of p53 in the treatment of cancers. The transcription factor E2F1 is controlled by binding of the tumor suppressor pRB, and induces apoptosis by activating the gene, an upstream activator of p53, when deregulated from pRB by loss of pRB function.

Evolutionary Adaptations in Biliverdin Reductase B: Insights into Coenzyme Dynamics and Catalytic Efficiency.

Biliverdin reductase B (BLVRB) is a redox regulator that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductions of multiple substrates, including flavins and biliverdin-β. BLVRB has emerging roles in redox regulation and post-translational modifications, highlighting its importance in various physiological contexts. In this study, we explore the structural and functional differences between human BLVRB and its hyrax homologue, focusing on evolutionary adaptations at the active site and allosteric regions.

Metoprolol vs diltiazem for atrial fibrillation with rapid ventricular rate: Systematic review and meta-analysis of adverse events.

Background: Intravenous (IV) diltiazem and metoprolol are commonly used to achieve rate control for atrial fibrillation with RVR (Afib with RVR), and are both recommended as first-line by current guidelines. While prior studies investigated the efficacy of these medications, there is little evidence available regarding the risk of adverse events (AEs) with their use.

Methods: We identified randomized controlled trials (RCT) and observational studies reporting rates of AEs following administration of IV diltiazem and metoprolol for Afib with RVR by searching PubMed, SCOPUS, EMBASE, and Cochrane Library.

Metabolic Switch in Endocrine Resistant Estrogen Receptor Positive Breast Cancer.

Purpose: The development of endocrine resistance remains a significant challenge in the clinical management of estrogen receptor-positive () breast cancer. Metabolic reprogramming is a prominent component of endocrine resistance and a potential therapeutic intervention point. However, a limited understanding of which metabolic changes are conserved across the heterogeneous landscape of ER+ breast cancer or how metabolic changes factor into ER DNA binding patterns hinder our ability to target metabolic adaptation as a treatment strategy.

Novel interactions within the silent information regulator heterochromatin complex potentiate inter-subunit communication and gene repression.

Organisms with smaller genomes often perform multiple functions using one multi-subunit protein complex. The Silent Information Regulator complex (SIRc) carries out all of the core functions of heterochromatin. SIR complexes first drive the initiation and spreading of histone deacetylation in an iterative manner.

Genome sequencing reveals the impact of non-canonical exon inclusions in rare genetic disease.

Introduction: Advancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging sequencing technologies are now being deployed in the clinical setting to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive clinical genetic testing.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts.

Purpose: Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems.

Methods:  Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.

The effects of war-related experiences on mental health symptoms of individuals living in conflict zones: a longitudinal study.

On October 7, 2023, a large-scale attack in southern Israel and the subsequent war resulted in extensive loss of life and injuries, with many individuals experiencing traumatic losses, such as family members or close friends being killed or kidnapped. This study aims to longitudinally examine its effects on mental health, specifically, clinical symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD). We anticipated greater symptom severity among individuals who experienced traumatic loss, were forcibly displaced, or suffered income loss, as well as among women and members of ethnic minorities.

Reporting of cluster randomised crossover trials: extension of the CONSORT 2010 statement with explanation and elaboration.

This article presents the CONSORT (consolidated standards of reporting trials) extension for cluster randomised crossover trials. A cluster randomised crossover trial involves randomisation of groups of individuals (known as clusters) to different sequences of interventions over time. The design has gained popularity in settings where cluster randomisation is required because it can largely overcome the loss in power due to clustering in parallel cluster trials.

Elevated Levels of Serum Alpha-2-Macroglobulin Associate with Diabetes Status and Incident Cardiovascular Disease in Type 1 Diabetes.

Background: Atherosclerotic cardiovascular disease (CVD) is a major cause of death in individuals with type 1 diabetes mellitus (T1DM). However, conventional risk factors do not fully account for the increased risk. This study aimed to investigate whether serum proteins associate with diabetes status and the occurrence of CVD in T1DM.

Mucin5AC promotes breast cancer brain metastasis through cMET/CD44v6.

Purpose: Breast cancer (BC) brain metastasis (BrM) remains a significant clinical problem. Mucins have been implicated in metastasis; however, if they are also involved in BCBrM remains unknown. We queried BrM patient databases and found Mucin 5AC (MUC5AC) to be upregulated and therefore sought to define the role of MUC5AC in BCBrM.

Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation.

Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited.

Editorial: Climate change is a children's health hazard.

As temperatures defy heat records, it is difficult to ignore the implications of climate change for public health, including impacts on population health more specifically. In short, climate change is happening now and presents an immediate hazard to human health on a global scale. Age-related health effects are an inalienable truth; physiology is relatively universal, and so are the ways in which our bodies respond to different types and levels of exposures to environmental stressors at different lifestages.

The Colorado Heart Failure Acuity Risk Model: A Mortality Model for Waitlisted Cardiac Transplant Patients.

Background: Currently, there is no mathematical model used nationally to determine the medical urgency of patients on the heart transplant waitlist in the United States. While the current organ distribution system accounts for many patient factors, a truly objective model is needed to more reliably stratify patients by their medical acuity.

Objectives: The aim of the study was to develop risk scores (Colorado Heart failure Acuity Risk Model [CHARM] score) to predict mortality in adults waitlisted for heart transplant.

Nicotine and cannabis vaping among early high school adolescents: Disparities of use across sociodemographic characteristics and associations with psychosocial factors.

This study examines whether adolescent nicotine and cannabis vaping types (i.e., nicotine-only, cannabis-only, and dual use) differ across sociodemographic and school characteristics (e.

Sex and genetic background influence intravenous oxycodone self-administration in the hybrid rat diversity panel.

Opioid Use Disorder (OUD) is an ongoing worldwide public health concern. Genetic factors contribute to multiple OUD-related phenotypes, such as opioid-induced analgesia, initiation of opioid use, and opioid dependence. Here, we present findings from a behavioral phenotyping protocol using male and female rats from 15 genetically diverse inbred strains from the Hybrid Rat Diversity Panel (HRDP).

A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice.

Background: Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides.

The role of epidemiologists in addressing the public health consequences of the United States criminal legal system.

Exposure to the United States criminal legal system - whether through contact with law enforcement, incarceration in a jail or prison, or community supervision - is associated with a range of adverse health outcomes. There is mounting evidence that mass incarceration drives health inequities, particularly for Black, Indigenous, and People of Color. However, relative to its outsized impacts on health and health inequities, the criminal legal system has received limited attention in epidemiology.

Protocol for generating splice isoform-specific mouse mutants using CRISPR-Cas9 and a minigene splicing reporter.

Here, we present a protocol to alter the production of alternatively spliced mRNA variants, without affecting the overall gene expression, through CRISPR-Cas9-engineered genomic mutations in mice. We describe steps for designing guide RNA to direct Cas9 endonuclease to consensus splice sites, producing transgenic mice through pronuclear injection, and screening for desired mutations in cultured mammalian cells using a minigene splicing reporter. Splice isoform-specific mouse mutants provide valuable tools for genetic analyses beyond loss-of-function and transgenic alleles.

Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.