Introduction: The gut microbiome is believed to have a significant impact on health throughout the lifespan, and the influence of infant nutrition and other environmental factors are of particular interest in its development. The aim of this research project was to learn more about the microbiome and short chain fatty acid (SCFA) composition of toddlers of differing weights, considering birth history, environment, and diet. In East Tennessee, opioid misuse is a growing issue, and a number of participants in this study were exposed in utero. We also hoped to identify related effects on infant’s SCFA composition. Finally, it is known that twins share a variety of traits, but much about their microbiome is unknown. With several pairs of twins in the sample, we aimed to identify any associations with SCFAs in this group. Methods: With informed consent, the child’s history was obtained, including age, birth length and weight, delivery type (C-section or vaginal), and feeding method (breast, bottle fed, or both). The child’s current weight, height, and BMI percentile were determined. Caregivers completed a 90-question Block Questionnaire for Ages 2-7 Kids food frequency questionnaire, and results were analyzed by Berkeley Analytics Inc (dba NutritionQuest). Participant-provided stool samples were freeze-dried and ground, and SCFAs were extracted and analyzed by content area % and concentration ppm. Data analysis was generated using SAS software, Version 9.4 of the SAS System, Copyright © 2013 SAS Institute Inc. Results: Nine SCFAs were measured in duplicate, and the concentrations averaged. Statistical analysis included comparisons of SCFAs related to factors including weight status, infant feeding modality, twin status, and intrauterine drug exposure, and significance determined with a p value < 0.05. Results did not identify significant differences in individual SCFA concentrations between obese and non-obese toddlers, however concentrations of isobutyrate, isovaleric acid, and octanoic acid were greater in toddlers who were formula fed as infants versus toddlers who were breastfed, and those fed a combination of breastmilk, and formula. Analysis further revealed a higher mean concentration of caproic and propionic acid in twin subjects. Of particular interest, toddlers with a history of opioid exposure had higher mean concentrations of isovaleric and octanoic acids, but less isocaproic acid when compared to those who were not drug exposed. Further analysis will help determine if these findings may be related to nutrient intake, in particular dietary fiber intake.

Endomorphin 1 and 2 are two tetrapeptides recently isolated from bovine as well as human brains and proposed to be the endogenous ligand for the μ- opiate receptor Opioid compounds expressing μ-receptor preference are generally potent analgesics. The spinal cord dorsal horn is considered to be an important site for the processing of sensory information including pain. The discovery that endomorphins produced greater analgesia in mice upon intrathecal as compared to intracerebroventricular injections raises the possibility that dorsal horn neurons may represent the anatomic site upon which endomorphins exert their analgesic effects. We report here the detection of endomorphin 2-immunoreactive fiber-like elements in superficial layers of the rat dorsal horn by immunohistochemical techniques. Whole-cell patch recordings from substantia gelatinosa neurons of cervical spinal cord slices revealed two conspicuous effects of exogenously applied endomorphin 1 and 2: (i) depression of excitatory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (ii) hyperpolarization of substantia gelatinosa neurons. These effects were reversed by the selective μ-opiate receptor antagonist β-funaltrexamine. Collectively, the detection of endomorphin-like immunoreactivity in nerve fibers of the superficial layers and the inhibitory action of endomorphins on substantia gelatinosa neurons provide further support for a potential role of these two peptides in spinal nociception.

Nociceptin, also referred to as orphanin FQ, is believed to be the endogenous ligand for the ORL1. Nociceptin, when injected intracerebroventricularly to mice, produced hyperalgesia in behavioral tests. Recent studies have demonstrated the presence of ORL1 transcript in the spinal cord, and ORL1-like immunoreactivity has been localized to nerve fibers and somata throughout the spinal cord. Here, we report the localization of nociceptin-like immunoreactivity to fiber-like elements of the superficial layers of the rat dorsal horn by immunohistochemical techniques. Whole-cell recordings from substantia gelatinosa neurons in transverse lumbar spinal cord slices of 22-26-day-old rats showed that exogenous nociceptin at low concentrations (100-300 nM) depressed excitatory postsynaptic potentials evoked by stimulation of dorsal rootlets without causing an appreciable change of resting membrane potentials and glutamate- evoked depolarizations. At a concentration of 1 μM, nociceptin hyperpolarized substantia gelatinosa neurons and suppressed spike discharges. The hyperpolarizing and synaptic depressant action of nociceptin was not reversed by the known opioid receptor antagonist naloxone (1 μM). Our result provides evidence that nociceptin-like peptide is concentrated in nerve fibers of the rat dorsal horn and that it may serve as an inhibitory transmitter within the substantia gelatinosa.

Beta-arrestins have been suggested to regulate μ-, δ-, and κ-opioid receptor-mediated responses. In the present study, we examined the effects of pretreatment with β-arrestin-2 antibody on tail-flick inhibition induced by opioid receptor agonists in the mouse spinal cord. Intrathecal (i.t.) pretreatment with β-arrestin-2 antibody potentiated the antinociception induced by i.t.-administered μ-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) and endomorphin-1, but not endomorphin-2, the δ-opioid receptor agonist [D-Ala2]deltorphin II or the κ-opioid receptor agonist U50,488H. The present result suggests that β-arrestin-2 may tonically down-regulate a selected population of μ-opioid receptors activated by endomorphin-1 or DAMGO in the mouse spinal cord.

Previous research on college students has found that cooperation in iterated prisoner's dilemma game is correlated with preference for delayed rewards in studies of temporal discounting. The present study attempted to replicate this finding in a drug-dependent population. Thirty-one individuals who intranasally abuse prescription opioids participated in temporal discounting and iterated prisoner's dilemma game procedures during intake for a treatment study. Rate of temporal discounting was determined for each participant at two hypothetical reward magnitudes, as well as proportion of cooperation in a 60-trial iterated prisoner's dilemma game versus a tit-for-tat strategy. Cooperation in the prisoner's dilemma game and temporal discounting rates were significantly correlated in the predicted direction: individuals who preferred delayed rewards in the temporal discounting task were more likely to cooperate in the prisoner's dilemma game.

Naloxone (NAL) is administered parenterally or intranasally for treating opioid overdose. The short duration of action of NAL calls for frequent re-dosing which may be eliminated by the development of a transdermal system. This study aimed to assess the effect of microneedles on improving the skin permeation of NAL hydrochloride. In vitro permeation of NAL across intact and microneedle-treated (Dr. Pen™ Ultima A6) porcine skin was evaluated. The effect of microneedle length and application duration, and donor concentration on NAL permeation were investigated. In-vitro in-vivo correlation of the permeation results was done to predict the plasma concentration kinetics of NAL in patients. In vitro passive permeation of NAL after 6 h was observed to be 8.25±1.06 µg/cm2. A 56- and 37-fold enhancement was observed with 500 and 250 µm needles applied for 1 min, respectively. Application of 500 µm MNs for 2 min significantly reduced the lag time to ~ 8 min and increasing the donor concentration for the same treatment group doubled the permeation (p < 0.05). Modeling simulations demonstrated the attainment of pharmacokinetic profile of NAL comparable to those obtained with the FDA-approved intramuscular and intranasal devices. Microneedle-mediated transdermal delivery holds potential for rapid and sustained NAL delivery for opioid overdose treatment.

Purpose of review: Overdose deaths have increased significantly over the last 5 years. This review analyzes the severity and nature of the epidemic, its impact on society, factors driving the increase in mortality, special populations disproportionately affected, and solutions to decrease overdose deaths. A thorough understanding of opioid overdose rates and deaths position the reader to respond most effectively in their sphere of influence. Recent findings: Final statistics for 2017 show a continued worsening of the epidemic. Recent studies focus on the evolving role of synthetic fentanyl, risk factors for fatal overdose, variation of mortality across demographic and socioeconomic regions, and the effectiveness of harm reduction strategies such as naloxone. Summary: The national overdose death rate continues to rise unabated with a 9.6% increase during 2017, with an estimated cost over $550 billion in 2019. There are, however, effective strategies to identify and treat individuals at risk for a fatal overdose. The root cause of addiction is the brain’s response to despair, social stressors, and societal structural inequities. It is unlikely we will see a significant decrease in addiction and its consequences until these root causes are addressed. Additional research is needed on the role of social determinants in addiction, strategies to treat incarcerated individuals, the role of suicidal ideation in fatal overdose, and risk factors, and frequency of non-fatal overdose.

An alternative analgesic to morphine is methadone, which is used to control chronic pain and is used in opioid rehabilitation treatment programs due to methadone having a long half-life and being relatively inexpensive as compared to extended-release forms of morphine. Despite its benefits, methadone accumulates in adipose tissue due to being lipophilic, binds strongly to plasma proteins, and is metabolized in the liver by the cytochrome P450 system causing methadone levels to be variable and subject to influence according to the individual body compositions and concurrent use of cytochrome P450 inhibitors. In addition to methadone being able to cause both respiratory and central nervous system depression, methadone can also prolong the QT interval and cause potentially life-threatening arrhythmias including torsades de pointes. The susceptibility of unintentional overdosing of methadone due to its varied pharmacologic properties and potentially fatal induction of arrhythmias may cause the risks of methadone use to outweigh its benefits and therefore must be closely monitored.

Based on the growing importance of community engagement and the recognition of its importance by the American Association of Colleges of Pharmacy (AACP), the committee offers several examples of community engagement activities for consideration and replication by our academy and beyond. These activities, including those of winning institutions of the Lawrence J. Weaver Transformational Community Engagement Award, can be mapped to the core components of community engagement presented in Table 1. The committee, using an implementation readiness framework, provides the reader with insight into the challenges that may impact successful community engagement and encourages our academy to continue its work to support faculty capacity in this area. Toward that end, the committee offers a policy statement that encourages schools and colleges of pharmacy to have an office or designate a faculty member whose focus is specifically on community engagement. The committee also offers a recommendation that the core components be included in the criteria for the Weaver Award.

The increasing recidivism rate for African American female offenders is exacerbated by postrelease job candidates' difficulties with interviewing for employment. The purpose of this hermeneutical, phenomenological study was to examine experiences from postrelease, African American, female, opioid offenders when interviewing with potential employers. Critical race Black feminist theory was used as the ontological lens for this research. Criterion sampling was used to recruit 12 female African American opioid female research participants. Data collection occurred via 12 semistructured, face-to-face interviewees. Thematic analysis was used to develop common emergent themes from the lived experiences of postrelease, African American, female, opioid offenders. Results showed that postrelease, African American, female offenders experienced emotional responses such as stress, nervousness, and anxiety during the interview process. In addition, they feared rejection when informing potential employers about their criminal background. The findings are significant in developing training programs for transition, human service, and criminal justice agencies that can increase the chances of postoffender, African American, female, opioid drug offender employment and decrease recidivism.