Neurogenetic and Epigenetic Aspects of Cannabinoids.

Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise.

Dopaminylation in Psychostimulant Use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression.

Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler's group explored histone Arg (R) methylation in reward processing models. Damez-Werno (2016) reported that during human investigations and animal self-administration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc.

Neurobiology and Spirituality in Addiction Recovery.

This commentary explores the neurobiology of spirituality and asks whether it is possible or desirable to apply genetic engineering to increase human spiritual and religious experience - (gene-spirituality) to deal better with the ever-increasing catastrophes that face humanity? Neurological connections between spirituality and reward genes, reward deficiencies (RDS) (hypodopaminergia), the mirror neuron system, and the default mode network are examined. Some interventions from addiction medicine that may be useful to enhance the neuro-spirituality connectome identified as a cornerstone of the Purpose and Meaning of Life as Reward (PMLR) are identified as reasonable targets for interventions to treat RDS and balance DMN activity.

Long-Term Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin-23, Through Two Years: Results From a Phase III, Randomized, Double-Blind, Placebo-Controlled Study Conducted in Biologic-Naive Patients With Active Psoriatic Arthritis.

Objective: To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial.

Methods: In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24.

High Genetic Addiction Risk Score (GARS) in Chronically Prescribed Severe Chronic Opioid Probands Attending Multi-pain Clinics: an Open Clinical Pilot Trial.

Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hypodopaminergia.

Association Between Arsenic Exposure and Cardiovascular Disease.

Arsenic is a ubiquitously dispersed metalloid that has been implicated as the cause of various adverse health effects. Human exposure to arsenic primarily occurs through contaminated drinking water and dietary intake of rice and grains, posing a great public health risk to millions of people worldwide. High levels of arsenic have been positively associated with incident cardiovascular disease (CVD).

Improving naltrexone compliance and outcomes with putative pro- dopamine regulator KB220, compared to treatment as usual.

A recent analysis from Stanford University suggested that without any changes in currently available treatment, prevention, and public health approaches, we should expect to have 510,000 deaths from prescription opioids and street heroin from 2016 to 2025 in the US. In a recent review, Mayo Clinic Proceedings (October 2019), Gold and colleagues at Mayo Clinic reviewed the available medications used in opioid use disorders and concluded that in private and community practice adherence is more important as a limiting factor to retention, relapse, and repeat overdose. It is agreed that the primary utilization of known opioid agonists like methadone, buprenorphine and naloxone combinations, while useful as a way of reducing societal harm, is limited by 50% of more discontinuing treatment within 6 months, their diversion, and addiction liability.

The Clinical Features of Bronchiectasis Associated with Alpha-1 Antitrypsin Deficiency, Common Variable Immunodeficiency and Primary Ciliary Dyskinesia--Results from the U.S. Bronchiectasis Research Registry.

Objective: This study compares and contrasts the clinical features of non-cystic fibrosis bronchiectasis with 3 uncommon disorders known to be associated with bronchiectasis but with distinctly different underlying defined pathophysiologic derangements, namely severe alpha-1 antitrypsin deficiency (AATD), common variable immunodeficiency (CVI) and primary ciliary dyskinesia (PCD).

Methods: The Bronchiectasis Research Registry provides a central database for studying patients with non-cystic fibrosis bronchiectasis. This report consists of information from 13 U.

Marijuana Use and Cardiovascular Disease.

Marijuana is currently the most used illicit substance in the world. With the current trend of decriminalization and legalization of marijuana in the US, physicians in the US will encounter more patients using marijuana recreationally over a diverse range of ages and health states. Therefore, it is relevant to review marijuana's effects on human cardiovascular physiology and disease.

FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice.

β-Cell compensation is an essential mechanism by which β-cells increase insulin secretion for overcoming insulin resistance to maintain euglycemia in obesity. Failure of β-cells to compensate for insulin resistance contributes to insulin insufficiency and overt diabetes. To understand the mechanism of β-cell compensation, we characterized the role of forkhead box O1 (FoxO1) in β-cell compensation in mice under physiological and pathological conditions.