Safety strategies and harm reduction for methamphetamine users in the era of fentanyl contamination: A qualitative analysis.

INTRODUCTION: In the United States, methamphetamine use is increasing and the context of its use has changed, with reports of illicitly manufactured fentanyl being mixed with methamphetamine (either deliberately or inadvertently). We explore risk-mitigating actions taken by people who use drugs to protect their health when using methamphetamine in that context. METHODS: We conducted qualitative interviews with 48 adults (18+) who used methamphetamine in the past three months at two sites in Nevada, USA and two sites in New Mexico, USA. Interviews were recorded, transcribed, and analyzed using thematic analysis. RESULTS: Respondents described two rationales for employing harm reduction strategies. First, to prevent harm from methamphetamine containing illicit fentanyl, and second, to maintain their general wellbeing while using methamphetamine. Regarding methamphetamine containing illicit fentanyl, our findings highlight how respondents employ primary strategies like buying from trusted sources and secondary strategies such as spotting and selective use of harm reduction tools (i.e., fentanyl test strips) to reduce risks. To maintain their general wellbeing, participants reduced their use of methamphetamine as reasonably as possible, and used other substances like marijuana and alcohol alongside methamphetamine to counter the unwanted side effects of methamphetamine (i.e., hallucinations and paranoia). Use of these harm reduction strategies varied within situational and social contexts, and respondents usually developed these strategies based on their lived experiences. CONCLUSION: Our findings uniquely demonstrate that people who use methamphetamine prioritize community driven, trust-based strategies within their social networks to mitigate risks in a fentanyl-contaminated drug environment. Additionally, our results indicate that harm reduction behaviors are influenced by multilevel risk environments, which include social, physical, economic, and political factors. Overall, these results highlight the potential for targeted interventions at the network level, which are responsive to complexities and shifts in drug market dynamics- such as illicit fentanyl in methamphetamine.

Propagation of Pacemaker Activity and Peristaltic Contractions in the Mouse Renal Pelvis Rely on Ca2+-activated Cl- Channels and T-Type Ca2+ Channels.

The process of urine removal from the kidney occurs via the renal pelvis (RP). The RP demarcates the beginning of the upper urinary tract and is endowed with smooth muscle cells. Along the RP, organized contraction of smooth muscle cells generates the force required to move urine boluses toward the ureters and bladder. This process is mediated by specialized pacemaker cells that are highly expressed in the proximal RP that generate spontaneous rhythmic electrical activity to drive smooth muscle depolarization. The mechanisms by which peristaltic contractions propagate from the proximal to distal RP are not fully understood. In this study, we utilized a transgenic mouse that expresses the genetically encoded Ca2+ indicator, GCaMP3, under a myosin heavy chain promotor to visualize spreading peristaltic contractions in high spatial detail. Using this approach, we discovered variable effects of L-type Ca2+ channel antagonists on contraction parameters. Inhibition of T-type Ca2+ channels reduced the frequency and propagation distance of contractions. Similarly, antagonizing Ca2+-activated Cl- channels or altering the transmembrane Cl- gradient decreased contractile frequency and significantly inhibited peristaltic propagation. These data suggest that voltage-gated Ca2+ channels are important determinants of contraction initiation and maintain the fidelity of peristalsis as the spreading contraction moves further toward the ureter. Recruitment of Ca2+-activated Cl- channels, likely Anoctamin-1, and T-type Ca2+ channels are required for efficiently conducting the depolarizing current throughout the length of the RP. These mechanisms are necessary for the efficient removal of urine from the kidney.