Daily opioid and stimulant co-use and nonfatal overdoses in the context of social disadvantage: Findings on marginalized populations.

OBJECTIVE: Opioids and stimulants are increasingly implicated in overdose deaths, particularly among minoritized groups. We examined daily opioid and cocaine co-use, nonfatal overdoses, and naloxone carrying among minoritized people who inject drugs (PWID). METHODS: The study derived data from 499 PWID in Baltimore City, MD, recruited using street-based outreach between 2016 and 2019. Participants reported overdoses; sociodemographic characteristics; and use of nonmedical prescription opioids, heroin, cocaine, and naloxone. RESULTS: Among the participants, the mean age was 46, 34 % were female, 64 % self-identified as Black, and 53 % experienced recent homelessness. Black PWID, compared to White PWID, were as likely to use opioids and cocaine daily but were 61 % less likely to have naloxone. After controlling for sociodemographic characteristics, women (aOR:1.88, 95%CI: 1.14, 3.11), persons experiencing homelessness (aOR:3.07, 95%CI: 1.79, 5.24), and those who experienced a recent overdose (aOR:2.14, 95%CI: 1.29, 3.58) were significantly more likely to use opioids and any form of cocaine every day. In a subanalysis of only female PWID, females engaged in sex work (aOR:2.27, 95%CI: 1.02, 5.07) and females experiencing recent homelessness (aOR:5.82, 95%CI: 2.50, 13.52) were significantly more likely to use opioids and cocaine daily. Furthermore, females (aOR:1.69, 95%CI:1.03, 2.77), persons experiencing homelessness (aOR:1.94, 95%CI:1.16, 3.24), and those with higher educational attainment (aOR:2.06, 95%CI:1.09, 3.91) were more likely to often/always carry naloxone, while Black PWID were less likely to have naloxone (aOR:0.39, 95%CI:0.22, 0.69). CONCLUSIONS: These findings highlight the need for targeted naloxone distribution and other harm-reduction interventions among minoritized groups in urban areas.

Social Networks, Stigma, and Hepatitis C Care Among Women Who Inject Drugs: Findings from A Community Recruited Sample.

This study explores the role of perceived HCV stigma and social networks on HCV care among people who inject drugs (PWID) of both sexes, and solely among women who inject drugs (WWID). Data were from 269 HCV positive PWID, community-recruited through street-based outreach in Baltimore, MD. We defined HCV stigma based on participants' perceptions of treatment by others and their need to conceal their HCV status. Among WWID, HCV stigma was linked with decreased odds of undergoing liver disease staging (aOR = 0.33, 95% CI: 0.13,0.85) or to have attempted to get the HCV cure (aOR = 0.39, CI: 0.16,0.97), these associations were not evident in the overall sample with both sexes. Social network characteristics were significant correlates of HCV care in the overall sample, and these associations were stronger among WWID. WWID with more HCV positive social network members had higher odds of an HCV-related healthcare visit in the prior 12 months (aOR = 4.28, CI: 1.29,14.17) and to have undergone liver disease staging (aOR = 2.85, CI: 1.01,8.05). WWID with more social network members aware of the HCV cure were more likely to report an attempt at obtaining the HCV cure (aOR = 5.25, CI: 1.85,14.89). Our results suggest complexity in the role of social networks and stigma on HCV care.

Racial differences in overdose training, naloxone possession, and naloxone administration among clients and nonclients of a syringe services program.

OBJECTIVE: To evaluate racial (Black/White) differences in overdose response training and take-home naloxone (THN) possession and administration among clients and nonclients of the Baltimore syringe service program (SSP). METHODS: The study derived data from a cross-sectional survey of 263 (183 SSP clients, 80 nonclients) people who inject drugs (PWID). The study recruited SSP clients using targeted sampling and recruited nonclients through peer referral from April to November 2016. RESULTS: In our sample, 61% of the participants were Black, 42% were between the ages of 18 and 44, and 70% were males. SSP clients, regardless of race, were more likely to have received overdose response training than Black nonclients (Black clients AOR: 3.85, 95% CI: 1.88, 7.92; White clients AOR: 2.73, 95% CI: 1.29, 5.75). The study found no significant differences in overdose response training between Black and White nonclients. SSP clients and White nonclients were more likely to possess THN than Black nonclients (Black clients: AOR: 4.21, 95% CI: 2.00, 8.87; White clients: AOR: 3.54, 95% CI: 1.56, 8.04; White nonclients AOR: 4.49, 95% CI: 1.50,13.47). CONCLUSION: SSP clients were more likely to receive overdose response training than their nonclient peers who they referred to the study, illustrating the utility of SSPs in reaching PWID at high risk of overdose. We also observed that Black PWID, who did not access services at the SSP, were the least likely to possess THN, suggesting the need to employ outreach targeting Black PWID who do not access this central harm reduction intervention.

DMSO modifies the permeability of the zebrafish (Danio rerio) chorion-implications for the fish embryo test (FET).

Since 2007, when REACH came into force, the fish embryo test has received increasing attention as a potential alternative for the acute fish test. Due to its low toxicity and the ability to permeate biological membranes without significant damage to their structural integrity, dimethyl sulfoxide (DMSO) is a commonly used solvent in the fish embryo test. Little is known, however, about the membrane penetration properties of DMSO, the impact of different concentrations of DMSO on the potential barrier function of the zebrafish chorion and on changes in the uptake of chemicals into the embryo. Therefore, in the present study, the fluorescent dyes fluorescein (mol wt 332; Pow 3.4) and 2,7-dichlorofluorescein (mol wt 401; Pow 4.7), both substances with limited water solubility, were used to visualize the uptake into the egg as well as the accumulation in the embryo of the zebrafish depending on different concentrations of DMSO. The distribution of fluorescein within the egg compartments varied with DMSO concentration: When dissolved in 0.01% DMSO, fluorescein did not pass the chorion. In contrast, concentrations ≥ 0.1% DMSO increasingly facilitated the uptake into the perivitelline space. In contrast, the uptake of 2,7-dichlorofluorescein was not substantially increased with rising DMSO concentrations, indicating the importance of factors other than the solvent (e.g. mol wt). With respect to the fish embryo test, results indicate that DMSO may be used without complications as a solvent, however, only at a maximum concentration of 0.01% (0.1 mL/L) as already indicated in the OECD difficult substances paper (OECD, 2000).

Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise.

To examine the effect of caffeine ingestion on muscle glycogen utilization and the neuroendocrine axis during exercise, we studied 20 muscle glycogen-loaded subjects who were given placebo or caffeine (6 mg/kg) in a double blinded fashion 90 min before cycling for 2 h at 65% of their maximal oxygen consumption. Exercise-induced glycogen depletion in the thigh muscle was noninvasively measured by means of 13C nuclear magnetic resonance spectroscopy (NMR) spectroscopy, and plasma concentrations of substrates and neuroendocrine hormones, including beta-endorphins, were also assessed. Muscle glycogen content was increased 140% above normal values on the caffeine trial day (P < 0.001). After cycling for 2 h, caffeine ingestion was associated with a greater increase in plasma lactate (caffeine: +1.0 +/- 0.2 mmol/L; placebo, +0.1 +/- 0.2 mmol/L; P < 0.005), epinephrine (caffeine, +223 +/- 82 pg/mL; placebo, +56 +/- 26 pg/mL; P < 0.05), and cortisol (caffeine, +12 +/- 3 mg/mL; placebo, +2 +/- 2 mg/mL; P < 0.001) levels. However, plasma free fatty acid concentrations increased (caffeine, +814 +/- 133 mmol/L; placebo, +785 +/- 85 mmol/L; P = NS), and muscle glycogen content decreased (caffeine, -57 +/- 6 mmol/L muscle; placebo, -53 +/- 5 mmol/L muscle; P = NS) to the same extent in both groups. At the same time, plasma beta-endorphin levels almost doubled (from 30 +/- 5 to 53 +/- 13 pg/mL; P < 0.05) in the caffeine-treated group, whereas no change occurred in the placebo group. We conclude that caffeine ingestion 90 min before prolonged exercise does not exert a muscle glycogen-sparing effect in athletes with high muscle glycogen content. However, these data suggest that caffeine lowers the threshold for exercise-induced beta-endorphin and cortisol release, which may contribute to the reported benefits of caffeine on exercise endurance.

Unusual DNA structures at the integration site of an HIV provirus.

Supercoiled pHXBc2 DNA (containing the genome of the human immunodeficiency virus type 1 and human sequences) migrated more slowly than linear DNA in native and ethidium bromide agarose gel electrophoresis at 4.5 volts/cm, suggesting the presence of unusual DNA structures. S1 nuclease analysis of pHXBc2 revealed two S1 hypersensitive sites. Site I was located within a 25 bp direct repeat in host DNA 0.6 kB upstream from the 5' LTR. Site II was mapped 0.2 kB upstream from the vif gene start site. Sequence analysis showed that Site I sequences could assume different unusual DNA structures, whereas sequences at Site II could assume either slipped or H-DNA forms. Unusual DNA structures in host DNA may be associated with active chromatin regions and may favor proviral integration.