KCNQ potassium channels composed of KCNQ2 and KCNQ3 subunits give rise to the M-current, a slow-activating and non-inactivating voltage-dependent potassium current that limits repetitive firing of action potentials. KCNQ channels are enriched at the surface of axons and axonal initial segments, the sites for action potential generation and modulation. Their enrichment at the axonal surface is impaired by mutations in KCNQ2 carboxy-terminal tail that cause benign familial neonatal convulsion and myokymia, suggesting that their correct surface distribution and density at the axon is crucial for control of neuronal excitability. However, the molecular mechanisms responsible for regulating enrichment of KCNQ channels at the neuronal axon remain elusive. Here, we show that enrichment of KCNQ channels at the axonal surface of dissociated rat hippocampal cultured neurons is regulated by ubiquitous calcium sensor calmodulin. Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum. Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon. Consistently, hippocampal neuronal excitability is dampened by transient expression of wild-type KCNQ2 but not mutant KCNQ2 deficient in calmodulin binding. Furthermore, coexpression of mutant calmodulin, which can interact with KCNQ2/KCNQ3 channels but not calcium, reduces but does not abolish their enrichment at the axonal surface, suggesting that apo calmodulin but not calcium-bound calmodulin is necessary for their preferential targeting to the axonal surface. These findings collectively reveal calmodulin as a critical player that modulates trafficking and enrichment of KCNQ channels at the neuronal axon.

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Young black men who have sex with men (YBMSM) and young black transgender women (TGW) have experienced a stark disparity in HIV prevention and care. Resilience, collective resources to adapt stressors or adversities, may improve HIV prevention and care outcomes. The present study investigated the association of resilience-based factors with PrEP uptake and viral suppression from a socioecological perspective among YBMSM and young black TGW. Data were from the baseline cycle of the Neighborhoods and Networks (N2) Study, an ongoing cohort study of 16-34-year-old YBMSM and young black TGW in Chicago (n = 324). Confidant network-level and neighborhood affiliation variables were created to measure the social-environmental context of resilience. All analyses were stratified by participants' HIV status (184 HIV-negative participants and 140 HIV-positive participants). Among HIV-negative participants, having a parental figure within an individual's confidant network was significantly associated with a greater likelihood of PrEP use. Among HIV-positive participants, confidant network members' awareness of an individual's HIV status was associated with viral suppression. Social support resources from confidant networks could improve HIV prevention and care engagement among YBMSM and young black TGW. Understanding the social and environmental contexts of resilience resource is critical for HIV prevention and care engagement.

Background There is limited evidence on the impact of the use of progestin-only hormonal contraception (POC) on weight change. We conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial. Methods The ECHO trial was conducted at 12 sites in eSwatini, Kenya, South Africa and Zambia between December 2015 and October 2018. HIV negative, women aged 16–35 years, desiring contraception, were randomised (1:1:1) to either 3-monthly intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant or copper intrauterine device (IUD). Follow-up was up to 18 months. Weight (kg) was measured at baseline and study exit. Analysis was performed as intention to treat (ITT) and time on continuous contraceptive use. The primary outcome of this secondary analysis is weight change from study enrolment to the final visit at study month 12–18. The ECHO trial is registered with ClinicalTrials.gov, NCT02550067. Findings 7829 women were randomly assigned to DMPA-IM ( n = 2609), copper IUD ( n = 2607) or LNG implant ( n = 2613). The ITT population included 7014 women 2293 DMPA-IM group, 2372 copper IUD group and 2349 LNG group) who were not lost to follow-up, pregnant on study, or missing weight data. The mean weight increased in all groups but was significantly different in magnitude: 3.5 kg (SD = 6.3), 2.4 kg (SD = 5.9) and 1.5 kg (SD = 5.7) in the DMPA-IM, LNG implant and copper IUD groups, respectively. Comparative differences between groups were (2.02 kg (95% CI, 1.68, 2.36, p < 0.001) for DMPA-IM versus copper IUD, 0.87 kg (0.53,1.20 p < 0.001) for LNG implant compared to copper IUD and 1.16 kg (0.82, 1.50, p < 0.001) for DMPA-IM compared with LNG implant. Results for continuous contraceptive use were similar. Interpretation We found differences in weight gain between POC users compared to the non-hormonal copper IUD group over 12–18 months of use. Women using POCs should be counselled about this potential side effect when choosing a contraceptive method.