The spontaneous decline of insulin secretion (third phase) that occurs under a variety of secretory conditions is well documented and suggests a general impairment or desensitization of the secretory process. We have examined several aspects of Ca2+ flux as well as regulators of Ca-linked second messenger events in freshly isolated rat islets chronically stimulated with glucose over 24 h, a period that encompasses initial (hour 1), peak (hour 3), and subsequent impaired or desensitized (hour 20-22) secretion. In islets incubated for these periods in HB104 medium with 22 mM glucose, 45Ca2+ uptake did not vary (12.6 +/- 1.6 vs. 10.2 +/- 1.7 vs. 13.2 +/- 3.4 pmol Ca2+/islet.10 min at 1, 3, and 22 h, respectively). Chronic incubation in 2 mM glucose reduced total Ca2+ uptake at each of the time periods, but, again, uptake did not change with desensitization (9.8 +/- 1.4 vs. 6.6 +/- 2.1 vs. 7.8 +/- 2.3 pmol Ca2+/islet.10 min). In 11 mM glucose, the Ca channel antagonist verapamil (1-10 microM) reduced insulin secretion by 55-80% in a dose-dependent manner over 1-3 h; islets continuously exposed to verapamil escaped inhibition by 20 h even at the highest concentration. However, in islets first exposed to 10 microM verapamil only during 20-22 h, hourly insulin secretion was suppressed 25%, 45%, and 33% at 20, 21, and 22 h, respectively, indicating that glucose-desensitized islets were still sensitive to further inhibition of Ca channels. Staurosporine (1 microM), an inhibitor of protein kinase-C activity, progressively inhibited glucose-stimulated insulin secretion from 48% at 1 h to more than 80% by 3 h; again, this inhibitory effect was lost by 20 h of chronic staurosporine. When staurosporine was first administered at 20 h, insulin secretion was modestly suppressed and returned to control values in the next hour. With continuous glucose, the islet response to positive stimulation of endogenous C-kinase activity by carbachol was maintained. The Ca/calmodulin inhibitor trifluoroperazine also inhibited insulin secretion by 75-80% during 1-3 h and continued to exert inhibitory effects through 23 h of continuous administration. We conclude that even though insulin secretion has desensitized to glucose, 1) Ca2+ entry is unchanged and is still regulated by glucose, 2) voltage-dependent Ca channels are still sensitive to blockade by acute verapamil, but can desensitize to chronic verapamil; 3) stimulus-enhanced C-kinase activity may be especially labile during glucose-induced desensitization, while 4) possible Ca/calmodulin potentiation of secretion persists through the three secretory phases.(ABSTRACT TRUNCATED AT 400 WORDS)

IntroductionHIV care engagement is lower among black sexual-minority men relative to other racial/ethnic groups of sexual-minority men. Being in a primary relationship is generally associated with more successful HIV care engagement across various populations. However, among black sexual-minority men, the association between primary relationship status and HIV-related outcomes is inconsistent across the HIV care continuum. Given the ubiquity of mobile technology access and use among racial/ethnic minority communities, leveraging mobile technology for HIV care engagement appears a promising intervention strategy. This paper outlines the protocol of the LetSync study, a pilot randomised controlled trial of a mobile health app intervention developed using the Framework of Dyadic HIV Care Engagement to improve care-engagement outcomes among black sexual-minority male couples living with HIV.Methods and analysisEighty black sexual-minority men in couples (n=160) will be enrolled to pilot test the LetSync app. At least one member of each dyad must be both HIV-positive and self-identify as black/African-American. Couples will be randomised to either a waitlist-control arm or an intervention that uses relationship-based approach to improve HIV care engagement. We will assess feasibility and acceptability of trial procedures and intervention protocols based on predefined metrics of feasibility and acceptability. Execution of the study will yield the opportunity to conduct analyses to test the measurement and analysis protocol on antiretroviral therapy adherence by comparing the intervention and waitlist-control arms on self-reported and biological (hair sample) measures of adherence.Ethics and disseminationStudy staff will obtain electronic consent from all participants. This study has been approved by the University of California (UCSF) Institutional Review Board. Study staff will work with the Community Advisory Board at the UCSF Center for AIDS Prevention Studies Board to disseminate results to participants and the community via open discussions, presentations, journal publications and/or social media.Trial registration numberNCT04951544.

Background HIV disproportionately impacts Black men who have sex with men (MSM), and targeting the primary relationship (ie, couples) using mobile technology for health holds promise for HIV prevention. Web-based recruitment of MSM is commonly employed in HIV prevention and intervention research. However, little known about recruiting Black MSM couples on the internet in the United States. Objective This study describes the process of recruiting Black MSM couples over social networking and dating apps frequented by MSM. We describe the activities for recruiting, screening, and enrolling participants as part of a randomized trial employing a multipronged recruitment approach. Methods Black MSM in couples were recruited via three apps (ie, Jack’d, Adam4Adam, and Growlr) between May 2020 and March 2021 during the COVID-19 pandemic in the United States. Black MSM couples were eligible if one or both partners are Black, MSM, and living with HIV, and if both partners were 18 years or older, and have been together for at least 2 months in what they both consider a primary relationship (ie, one in which both partners reported feeling most committed to over any other partner or relationship). Results A total of 10 Black MSM couples (n=20) were enrolled via social networking apps. App recruitment activities were a combination of passive (eg, in-app advertisements) and active (eg, direct messaging of users) engagement. Recruitment approaches varied by the social networking app owing to differences in app features. A full-time recruiter experienced challenges such as bugs (ie, technical errors in computer program or system), navigating technical requirements specific to each app, and web-based harassment. Conclusions Despite challenges, it was possible to recruit Black MSM couples virtually into research as part of a multipronged recruitment strategy. We identify tips for using web-based dating and other social networking apps as part of a recruitment strategy in future research with Black MSM couples.

Background HIV disparities continue to be a significant challenge affecting Black sexual minority men in the United States. Inadequate engagement and retention of patients in HIV care has been associated with poor health outcomes. Interventions to improve sustained commitment to HIV care are needed. Mobile health interventions can help facilitate access to and use of HIV health services, particularly among individuals at risk for disengaging with care. Objective We designed the LetSync app wireframes for a mobile health intervention using a couple-centered design approach to improve HIV engagement and treatment among Black sexual minority men and their partners. The objective of this study was to gauge future app user interest and elicit feedback to improve the design, development, and usability of the LetSync app. Methods We conducted in-depth interviews with 24 Black sexual minority men to assess the acceptability of the LetSync app wireframes between May 2020 and January 2021. Participants reviewed the LetSync app wireframes and provided feedback regarding perceived usefulness and interest in future app use and suggestions for improvement. Results Participants indicated interest in the future LetSync app and noted that the wireframes’ features were acceptable and usable. In our study, the future LetSync app was frequently referred to as a potential resource that could help facilitate users’ engagement in HIV care through the following mechanisms: enable scheduling of appointments and timely reminders for clinic visits; help improve HIV medication adherence; encourage and motivate participants to ask questions to their health care provider and stay engaged in conversations during clinic visits; facilitate effective communication by assisting couples with planning, coordination, and management of daily routines; help participants understand their partner’s health needs, including access to and use of health care services; and facilitate participants’ ability to improve their relationship skills, partner support, and self-efficacy in managing conflict. In addition to near-universal interest in potential daily app use, study participants indicted that they would recommend the LetSync app to other family members, friends, and people in their social networks who are living with HIV. Conclusions Our findings revealed considerable interest in future app use for HIV care management, which could possibly increase the chance of the LetSync app being successfully adopted by Black sexual minority men in couples. Owing to its interactive and couple-centered approach, the LetSync app could help improve communication between Black sexual minority men and their partners and health providers. In addition, the LetSync app could provide an acceptable modality for these men to receive support in accessing HIV care services.

BACKGROUND HIV disproportionately impacts Black men who have sex with men (MSM) and targeting the primary relationship (i.e., couples) using mobile technology for health (mHealth) holds promise for HIV prevention. Online recruitment of MSM is commonly employed in HIV prevention and intervention research. However, little known about recruiting Black MSM couples online in the US. OBJECTIVE To describe the process of recruiting Black MSM couples over social networking and dating applications (apps) frequented by MSM. We describe the activities for recruiting, screening, and enrolling participants as part of a randomized trial employing a multipronged recruitment approach. METHODS Black MSM in couples were recruited via three apps (i.e., Jack’d, Adam4Adam, and Growlr) between May 2020 and March 2021, during the COVID-19 pandemic in the US. Black MSM couples were eligible if one or both partners are Black, MSM, and living with HIV; and if both partners were 18 years or older, have been together for at least two months in what they both consider to be a primary relationship (i.e., one in which both partners reported feeling most committed to over any other partner or relationship). RESULTS A total of 25 couples (n = 50) were enrolled; of these, 10 couples (n = 20) were enrolled via apps. App recruitment activities were a combination of passive (e.g., in-app advertisements) and active (e.g., direct messaging of users) engagement. A full-time staff recruiter experienced challenges such as bugs (i.e., technical errors in computer program or system), navigating idiosyncratic advertising and technical requirements specific to each app, and online harassment from users. CONCLUSIONS Despite challenges, it was possible to recruit Black MSM couples virtually into research as part of a multipronged recruitment strategy. We identify tips for using online dating and other social-networking apps as part of a recruitment strategy in future research with Black MSM couples.