Buprenorphine, oxycodone, hydrocodone, and methadone mortality in the United States (2010‒2017).

Objective: Opioid overdose survivors present to emergency departments (EDs) and many EDs have developed programs to initiate buprenorphine. The impact of the increasing use of buprenorphine in ED and by other providers is unknown while opioid mortality continues to rise. Public mortality data do not distinguish buprenorphine from other prescription opioids.

Identifying and quantifying exposures involving counterfeit opioid analgesic products.

Introduction: The increasing presence of counterfeit opioid drugs in the United States can contaminate data collection systems and confound estimates derived from surveillance of the opioid epidemic. Data sources and analyses that can quantify the contribution of counterfeit opioid products are needed to provide accurate and timely data to inform public health responses. We describe a novel approach to identify and quantify intentional abuse and misuse exposures involving suspected counterfeit opioid products in United States poison center data.

Clinical Effects of Psychedelic Substances Reported to United States Poison Centers: 2012 to 2022.

Study Objective: Psychedelic substances use is increasing in the United States (US). The approval of new psychedelic drugs and legalization of natural psychedelic substances will likely further increase exposures and subsequent adverse events. The study objective is to describe the clinical effects, therapies, and medical outcomes of patients with psychedelic exposures reported to US poison centers.

Estimating the Prevalence of Using Suspected Counterfeit Medications in the General Population.

Introduction: Counterfeit medications, sometimes referred to as "fake" or falsified drugs or pills, are drugs that are illicitly manufactured but designed to look like legitimate pharmaceuticals. Counterfeit medications are a growing public health concern. This study estimated the prevalence of self-reported use of suspected counterfeit medications by adults in the US and to assess what ingredients these individuals suspected were in the counterfeit medications.

PKCδ Regulates Chromatin Remodeling and DNA Repair through SIRT6.

Unlabelled: Irradiation (IR) is a highly effective cancer therapy; however, IR damage to tumor-adjacent healthy tissues can result in significant comorbidities and potentially limit the course of therapy. We have previously shown that protein kinase C delta (PKCδ) is required for IR-induced apoptosis and that inhibition of PKCδ activity provides radioprotection in vivo. Here we show that PKCδ regulates histone modification, chromatin accessibility, and double-stranded break (DSB) repair through a mechanism that requires Sirtuin 6 (SIRT6).

Initiation Patterns and Transitions Among Adults Using Stimulant Drugs: Latent Transition Analysis.

Background: The fourth wave of the drug overdose epidemic in the United States includes increasing rates of stimulant-involved overdose. Recent studies of transitions leading to stimulant misuse have shown complex patterns that are not universally applicable because they have isolated individual populations or individual behaviors. A comprehensive analysis of transitions between behaviors and the associations with present-day problematic drug use has not been conducted.

PKCδ regulates chromatin remodeling and DNA repair through SIRT6.

Protein kinase C delta (PKCδ) is a ubiquitous kinase whose function is defined in part by localization to specific cellular compartments. Nuclear PKCδ is both necessary and sufficient for IR-induced apoptosis, while inhibition of PKCδ activity provides radioprotection How nuclear PKCδ regulates DNA-damage induced cell death is poorly understood. Here we show that PKCδ regulates histone modification, chromatin accessibility, and double stranded break (DSB) repair through a mechanism that requires SIRT6.

Transition from Transient DNA Rereplication to Inherited Gene Amplification Following Prolonged Environmental Stress.

Cells require the ability to adapt to changing environmental conditions, however, it is unclear how these changes elicit stable permanent changes in genomes. We demonstrate that, in response to environmental metal exposure, the metallothionein (MT) locus undergoes DNA rereplication generating transient site-specific gene amplifications (TSSGs). Chronic metal exposure allows transition from MT TSSG to inherited MT gene amplification through homologous recombination within and outside of the MT locus.

Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells.

(1) Background: Metal homeostasis is an important part of cellular programs and is disrupted when cells are exposed to carcinogenic heavy metals. Metal response is mediated by the metal response element transcription factor MTF-1. However, where MTF-1 binds and how that binding changes in response to heavy metals, such as cadmium, remains unknown.

Atypical histone targets of PHD fingers.

Plant homeodomain (PHD) fingers are structurally conserved zinc fingers that selectively bind unmodified or methylated at lysine 4 histone H3 tails. This binding stabilizes transcription factors and chromatin-modifying proteins at specific genomic sites, which is required for vital cellular processes, including gene expression and DNA repair. Several PHD fingers have recently been shown to recognize other regions of H3 or histone H4.

Characteristics of poisonings involving ketamine in the United States, 2019-2021.

Background: The use of ketamine, a controlled dissociative anesthetic, has become more widespread in recent years with recreational/nonmedical use increasing and ketamine becoming more widely available in clinics to treat depression.

Aims: We examined recent trends in adverse effects related to ketamine use.

Methods: US National Poison Control data were examined, focusing on ketamine exposures among those aged ⩾13 between 2019 and 2021 ( = 758).

Extrachromosomal Circular DNA from TCGA Tumors Is Generated from Common Genomic Loci, Is Characterized by Self-Homology and DNA Motifs near Circle Breakpoints.

Extrachromosomal circular DNA has emerged as a frequent genomic alteration in tumors. High numbers of circular DNAs correspond to poor prognosis suggesting an important function in tumor biology. However, despite mounting evidence supporting the importance of circular DNA, little is known about their production, maintenance, or selection.

Clustering patterns in polysubstance mortality in the United States in 2017: a multiple correspondence analysis of death certificate data.

Purpose: The main goal of this analysis was to identify mortality patterns apparent when many drug classes are analyzed together.

Methods: The Drug Involved Mortality database is a registry of drug terms mentioned on death certificates of all drug-related deaths in the United States. Means of total number of drugs involved and percentages of specific drug combinations were calculated.

SIX1 reprograms myogenic transcription factors to maintain the rhabdomyosarcoma undifferentiated state.

Rhabdomyosarcoma (RMS) is a pediatric muscle sarcoma characterized by expression of the myogenic lineage transcription factors (TFs) MYOD1 and MYOG. Despite high expression of these TFs, RMS cells fail to terminally differentiate, suggesting the presence of factors that alter their functions. Here, we demonstrate that the developmental TF SIX1 is highly expressed in RMS and critical for maintaining a muscle progenitor-like state.

Collective regulation of chromatin modifications predicts replication timing during cell cycle.

Replication timing (RT) associates with genome architecture, while having a mixed relationship to histone marks. By profiling replication at high resolution and assessing broad histone marks across the cell cycle at the resolution of RT with and without genetic perturbation, we address the causal relationship between histone marks and RT. Four primary chromatin states, including an uncharacterized H3K36me2 state, emerge and define 97% of the mappable genome.

Drug product dispensing and estimates of use in a general population survey as a signal detection problem.

Purpose: Understanding potential bias due to rarity of the outcome is important when monitoring newly approved drugs and drugs with low availability to the general public. Although there is an increasing use of online surveys to investigate health outcomes, the limits of inference due to drug availability have not been studied. The goal of this study was to quantify the relationship between dispensing of prescription drugs and estimates of use in an online general population survey.

Measuring prescription opioid misuse and its consequences.

Aims: Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the medications involved, user characteristics and other factors needed to address the epidemic.

Methods: A strategy of mosaic surveillance has evolved.

Association of Medical Stimulants With Mortality in the US From 2010 to 2017.

This cross-sectional study examines the association of medical stimulants with mortality in the US from 2010 to 2017.