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IntroductionDNA methylation (DNAm), an epigenetic mechanism, has been associated with opioid use disorder (OUD) in preclinical and human studies. However, most of the studies have focused on DNAm at CpG sites. DNAm at non-CpG sites (mCpHs, where H indicates A, T, or C) has been recently shown to have a role in gene regulation and to be highly abundant in neurons. However, its role in OUD is unknown. This work aims to evaluate mCpHs in the human postmortem orbital frontal cortex (OFC) in the context of OUD.MethodsA total of 38 Postmortem OFC samples were obtained from the VA Brain Bank (OUD = 12; Control = 26). mCpHs were assessed using reduced representation oxidative bisulfite sequencing in neuronal nuclei. Differential analysis was performed using the “methylkit” R package. Age, ancestry, postmortem interval, PTSD, and smoking status were included as covariates. Significant mCpHs were set at q-value < 0.05. Gene Ontology (GO) and KEGG enrichment analyses were performed for the annotated genes of all differential mCpH loci using String, ShinyGO, and amiGO software. Further, all annotated genes were analyzed using the Drug gene interaction database (DGIdb).ResultsA total of 2,352 differentially methylated genome-wide significant mCpHs were identified in OUD, mapping to 2,081 genes. GO analysis of genes with differential mCpH loci showed enrichment for nervous system development (p-value = 2.32E-19). KEGG enrichment analysis identified axon guidance and glutamatergic synapse (FDR 9E-4–2.1E-2). Drug interaction analysis found 3,420 interactions between the annotated genes and drugs, identifying interactions with 15 opioid-related drugs, including lofexidine and tizanidine, both previously used for the treatment of OUD-related symptoms.ConclusionOur findings suggest a role of mCpHs for OUD in cortical neurons and reveal important biological pathways and drug targets associated with the disorder.

Recently, sensory threshold concepts have been expanded to include affective perceptions of foods and beverages, especially measures of product rejection; however, each threshold interpretation depends largely on the methodology employed. By substituting cricket powder for whole-wheat flour in snack crackers (0%, 5%, 10%, 15%, and 20%), we proposed modifications to two existing threshold methodologies: a modified consumer rejection threshold (M-CRT) using a 2-alternative choice (2-AC) preference test with “no preference” option; and a modified hedonic rejection threshold (M-HRT) based on less-than-neutral hedonic scores according to a one-sample t-test. We also proposed two new concepts: a rejection tolerance threshold (RTT) and an associated rejection range (RR), based on a binomial acceptability question and a probit regression model. These new methods provide more realistic interpretations of rejection-type thresholds based on user-defined allowable rejection levels, or “rejection tolerance” (for RTT), and a model-derived stimulus range (RR) to capture the rejection level of interest while providing flexibility for product formulation. All thresholds were investigated separately for color, flavor, texture and overall perception, elucidating differential sensorial effects of our novel ingredient on the food matrix. We suggest that conducting all demonstrated techniques in a single testing session gives a more expansive view of rejection thresholds while requiring minimal additional resources.

Logging is a dangerous occupation, as documented through reported injuries and fatalities. Accidents in the logging industry account for pain, suffering, employee turnover, and high insurance costs. Worker injuries and high insurance costs, in addition to other factors, may be minimized and reduced through safety education and improved logging practices. Furthermore, the injured logger, or logger with a disability may return to logging or other employment through development of viable medical and vocational rehabilitation planing. This article addresses the economic impact of logging, reviews logging injuries, describes a safety program designed to reduce logging injures, discusses rehabilitation considerations for specific injuries, and outlines particular reemployment prospects for loggers with disabilities. [ABSTRACT FROM AUTHOR]