Synopsis of the 2023 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline for the Management of Bipolar Disorder.

The US Department of Veterans Affairs (VA) and Department of Defense (DOD) Work Group revised the 2013 VA/DOD Clinical Practice Guideline (CPG) for the Management of Bipolar Disorder (BD). This paper reviews the 2023 CPG and its development process, including how recommendations were made for evidence-based treatment in BD. Subject experts and key stakeholders developed 20 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method.

Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism.

Background: A large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.

Methods: By applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.

Results: Using gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D.

2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Management of Headache.

Description: Headache medicine and therapeutics evidence have been rapidly expanding and evolving since the 2020 U.S. Department of Veterans Affairs (VA) and U.

Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.

Atrial arrhythmias occur in 20-40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter-defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene-positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin-2 (PKP2).

Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats.

Sample preparation and data collection for serial block face scanning electron microscopy of mammalian cell monolayers.

Volume electron microscopy encompasses a set of electron microscopy techniques that can be used to examine the ultrastructure of biological tissues and cells in three dimensions. Two block face techniques, focused ion beam scanning electron microscopy (FIB-SEM) and serial block face scanning electron microscopy (SBF-SEM) have often been used to study biological tissue samples. More recently, these techniques have been adapted to in vitro tissue culture samples.

Neonatal Diazepam Exposure Decreases Dendritic Arborization and Spine Density of Cortical Pyramidal Neurons in Rats.

Objective: Benzodiazepines are extensively utilized in pediatric anesthesia and critical care for their anxiolytic and sedative properties. However, preclinical studies indicate that neonatal exposure to GABAergic drugs, including benzodiazepines, leads to long-term cognitive deficits, potentially mediated by altered GABAergic signaling during brain development. This preclinical study investigated the impact of early-life diazepam exposure on cortical neuronal morphology, specifically exploring dendritic arborization and spine density, crucial factors in synaptogenesis.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity.

The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

Description: The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder.

Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions.

The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.

A Randomized Phase 2 Study to Evaluate Efficacy and Safety of AR36 for Prevention of Acute Mountain Sickness.

Introduction: AR36 is a pharmaceutical-grade plant extract used to support cardiovascular health in traditional Chinese medicine. Studies suggest that AR36 may prevent acute mountain sickness (AMS) during gradual ascent to high altitude. This randomized, placebo-controlled Phase 2 trial aimed to evaluate dosing regimens and assess efficacy and safety of AR36 for AMS prevention during rapid ascent.

Diagnosis and Treatment of Low Back Pain: Synopsis of the 2021 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline.

Low back pain is a significant issue in the US Department of Veterans Affairs and Department of Defense populations as well as the general US population at large. This type of pain can be distressing to those who experience its effects, leading patients to seek relief of their symptoms. In 2022, leadership within the US Department of Veterans Affairs and US Department of Defense approved a joint clinical practice guideline for the management of low back pain.

The Effect of Route of Administration and Vehicle on the Pharmacokinetics of THC and CBD in Adult, Neonate, and Breastfed Sprague-Dawley Rats.

Basic pharmacokinetic (PK) and pharmacodynamic models of the phytocannabinoids Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are critical for developing translational models of exposure and toxicity. The neonatal period is a particularly important time to study the effects of cannabinoids, yet there are few studies of cannabinoid PKs by different routes such as direct injection or breast milk ingestion. To study this question, we have developed a translationally relevant rodent model of perinatal cannabinoid administration by measuring plasma levels of THC and CBD after different routes and preparations of these drugs.

The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication.

Generation of virus-host protein-protein interactions (PPIs) maps may provide clues to uncover SARS-CoV-2-hijacked cellular processes. However, these PPIs maps were created by expressing each viral protein singularly, which does not reflect the life situation in which certain viral proteins synergistically interact with host proteins. Our results reveal the host-viral protein-protein interactome of SARS-CoV-2 NSP3, NSP4, and NSP6 expressed individually or in combination.

Salt-inducible kinases are required for glucose uptake and insulin signaling in human adipocytes.

Objective: Salt-inducible kinase 2 (SIK2) is abundantly expressed in adipocytes and downregulated in adipose tissue from individuals with obesity or insulin resistance. The main aims of this work were to investigate the involvement of SIKs in the regulation of glucose uptake in primary mature human adipocytes and to identify mechanisms underlying this regulation.

Methods: Primary mature adipocytes were isolated from human, rat, or mouse adipose tissue and treated with pan-SIK inhibitors.

Dyslipidemia Update.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. The development and progression of atherosclerotic CVD are largely dependent on a multitude of modifiable and nonmodifiable risk factors. Current therapeutic strategies involve risk factor modification, especially dyslipidemia.

Nanogold based protein localization enables subcellular visualization of cell junction protein by SBF-SEM.

Recent advances in volume electron microscopy (vEM) allow unprecedented visualization of the electron-dense structures of cells, tissues and model organisms at nanometric resolution in three dimensions (3D). Light-based microscopy has been widely used for specific localization of proteins; however, it is restricted by the diffraction limit of light, and lacks the ability to identify underlying structures. Here, we describe a protocol for ultrastructural detection, in three dimensions, of a protein (Connexin 43) expressed in the intercalated disc region of adult murine heart.

3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen .

Microsporidia are an early-diverging group of fungal pathogens that infect a wide range of hosts. Several microsporidian species infect humans, and infections can lead to fatal disease in immunocompromised individuals. As obligate intracellular parasites with highly reduced genomes, microsporidia are dependent on metabolites from their hosts for successful replication and development.

A Spatial Memory Deficit in Male But Not Female Rats After Neonatal Diazepam Exposure: A New Model for Developmental Sedative Neurotoxicity.

Background: Developmental anesthetic neurotoxicity is well described in animal models for GABAergic, sedating drugs. Here we investigate the role of the benzodiazepine, diazepam on spatial and recognition memory of young adult rats after neonatal exposure.

Methods: On postnatal day 7, male (n = 30) and female (n = 30) rats were exposed to diazepam (30 mg/kg intraperitoneally) or vehicle.