Activation of CB2 Receptors by (-)-Cannabichromene but Not (+)-Cannabichromene.

Introduction: Cannabichromene (CBC) is a minor constituent of cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC, or both can mediate these effects. In this study, we investigate the activity of the CBC enantiomers at CB1, CB2, and Transient receptor potential ankyrin 1 (TRPA1) receptors in vitro. Materials and Methods: CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. Results: The (-)-CBC activated CB2 with an EC50 of 1.5 µM, to a maximum of 60% of (-)CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (-)-CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)-CBC activated TRPA1; at 30 µM (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. Discussion: It is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer.

Needs & networks: understanding the role and impact of social networks on HIV (self-)testing among GBMSM and trans people in England and Wales.

BACKGROUND: Understanding how HIV self-testing (HIVST) can meet the testing needs of gay, bisexual and other men who have sex with men (GBMSM) and trans people whose social networks vary is key to upscaling HIVST implementation. We aim to develop a contextual understanding of social networks and HIV testing needs among GBMSM (cis and transgender) and trans women in SELPHI (An HIV Self-testing Public Health Intervention), the UK's largest randomised trial on HIVST. METHODS: This study re-analysed qualitative interviews conducted from 2015 to 2020. Forty-three in-person interviews were thematically analysed using the Framework Method. Our analytic matrix inductively categorised participants based on the unmet needs for HIV testing and the extent of social network support. The role of social networks on HIVST behaviour was explored based on individuals' testing trajectories. RESULTS: Four distinct groups were identified based on their unmet testing needs and perceived support from social networks. Optimisation advocates (people with high unmet needs and with high network support, n = 17) strived to tackle their remaining barriers to HIV testing through timely support and empowerment from social networks. Privacy seekers (people with high unmet needs and with low network support, n = 6) prioritised privacy because of perceived stigma. Opportunistic adopters (people with low unmet needs and with high network support, n = 16) appreciated social network support and acknowledged socially privileged lives. Resilient testers (people with low unmet needs and with low network support, n = 4) might hold potentially disproportionate confidence in managing HIV risks without sustainable coping strategies for potential seroconversion. Supportive social networks can facilitate users' uptake of HIVST by: (1) increasing awareness and positive attitudes towards HIVST, (2) facilitating users' initiation into HIVST with timely support and (3) affording participants an inclusive space to share and discuss testing strategies. CONCLUSIONS: Our proposed categorisation may facilitate the development of differentiated person-centred HIVST programmes. HIVST implementers should carefully consider individuals' unmet testing needs and perceived levels of social support, and design context-specific HIVST strategies that link people lacking supportive social networks to comprehensive HIV care.

Experiences of mpox illness and case management among cis and trans gay, bisexual and other men who have sex with men in England: a qualitative study.

Background: The 2022-2024 global mpox outbreak, occurring primarily in the sexual networks of gay, bisexual and other men who have sex with men (GBMSM), has not been accompanied by a focus on patient perspectives of illness. We explore the experiences of GBMSM diagnosed with mpox in England to understand needs for social and clinical support. Methods: In-depth interviews (March/July 2023) were conducted with 22 GBMSM diagnosed with mpox in 2022, randomly selected from a national mpox surveillance database, and 4 stakeholders from clinical/community-based organisations. Interviews covered experiences of illness, testing, diagnosis, treatment and contact tracing, and were recorded, transcribed and analysed with a thematic framework. Findings: Media coverage drawing on homophobic stereotypes around sex between men contributed to feelings of stigma and shame. GBMSM living with HIV appeared to cope better with mpox stigma, drawing on their experiences of being diagnosed with HIV for resilience. Younger GBMSM with less experience of stigmatising illness found mpox diagnosis more traumatic and sometimes required support beyond what was provided. Accessing testing could be complicated when healthcare professionals did not recognise mpox symptoms. Men felt information on course of illness, isolation and vaccination after recovery was often inconsistent and contradictory. GBMSM described that care from sexual health and infectious disease units usually better met their emotional and medical needs. This was frequently linked by men to these services having skills in working with the GBMSM community and managing infection risk sensitively. General hospital services and centralised contact tracing could increase feelings and experiences of stigma as some staff were perceived to lack skills in supporting GBMSM and, sometimes, clinical knowledge. Long-term impacts described by men included mental health challenges, urethral/rectal symptoms and life-changing disability. Interpretation: In this study stigma was a central feature of mpox illness among GBMSM and could be exacerbated or lessened depending on the clinical and social support provided. Involving communities affected by outbreaks in co-producing, planning and delivering care (including contact-tracing) may help improve support provided. Funding: TCW, AJR, AS and FMB received support from the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research Programme (Ref: NIHR202038). CS and JS receive support from the National Institute for Health and Care Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at UCL in partnership with UKHSA; RV receives support from the NIHR HPRU in Emerging and Zoonotic Infections and NIHR HPRU in Gastrointestinal Infections. The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency, World Health Organization or the Department of Health and Social Care.

Advantages of a synchrotron light source for fluorescence-detected linear dichroism.

Fluorescence-detected linear dichroism (FD-LD) enables one to collect linear dichroism spectra for oriented fluorophores in the presence of other absorbing species and light scattering. The experiment proceeds by scanning the excitation wavelength and using a filter to collect only emitted photons from the fluorophore. Thus, it has the potential to give data with enhanced selectivity and quality. By using a synchrotron radiation light source and fluorescence-detection, we show data for a range of fluorophores in different orienting environments. Film and flow-oriented FD-LD spectra were collected down to 170 nm. Even for flow-oriented liposomes, we have data collected down to 210 nm. For strongly scattering samples, for example, liposomes, FD-LD has the clear advantage that scattering is absent for the longer wavelength fluorescence photons. The collimated and smaller beam size of the synchrotron radiation also gives rise to sharper and more well-defined features in the spectra.

Linear dichroism and linearly polarised luminescence spectra of oriented samples collected on a new integrated instrument.

Linearly polarised luminescence (LPL) has a wide range of potential applications giving optical and geometric parameters for oriented lumiphores. In this work we present the first wavelength scanned LPL spectra. Analytes are either oriented on stretched polyethylene films or in flow. Applications of the wavelength-dependence of g-factors are illustrated.

Experiences with health care services and HIV testing after sexual assault in cisgender gay, bisexual and other men who have sex with men and transgender people.

OBJECTIVES: This qualitative sub-study aimed to explore how cisgender gay, bisexual, and other men who have sex with men (cis-GBMSM) and transgender people who reported non-consensual sex (NCS) accessed health care services, what barriers they faced, and how this experience influenced subsequent HIV testing. METHODS: SELPHI is an online randomized controlled trial evaluating both acceptability and efficiency of HIV-self testing among cis-GBMSM and transgender people. Semi-structured interviews were conducted, audio-recorded, transcribed, and analysed through a framework analysis, as a qualitative sub-study. We identified narratives of NCS from interviews and investigated experiences of cis-GBMSM and transgender people accessing health care services following sexual assault. RESULTS: Of 95 participants, 15 (16%) spontaneously reported NCS. Participants reported a broad range of NCS, including partner's coercive behaviours, non-consensual removal of condoms, and rapes. All feared HIV transmission, leading them to test for HIV, underlining a marked lack of awareness of post-exposure prophylaxis (PEP). Most had negative experiences in communicating with reception staff in sexual health clinics following these incidents. A lack of confidentiality and empathy was described in these situations of psychological distress. Clinic visits were primarily focused on testing for HIV and sexually transmitted infection, and generally no specific psychological support was offered. Getting a negative HIV result was a key step in regaining control for people who experienced NCS. CONCLUSIONS: Sexual health care providers should take care to more fully address the issue of NCS with cis-GBMSM and transgender people when it arises. Recognizing and managing the emotional impact of NCS on affected patients would prevent negative experiences and increase confidence in care.

Integrated Circular Dichroism and Circularly Polarized Luminescence Measurements.

Circularly polarized luminescent (CPL) systems have a plethora of potential applications owing to their interesting excited-state properties. However, the progress in developing new chiral luminescence systems is significantly hindered by the lack of available instrumentation for the broader chemistry and materials science community to perform routine, reproducible measurements of chiral spectroscopies. In this work, we present data from an easy-to-use custom-built instrument based on a Jasco circular dichroism (CD) spectropolarimeter coupled with a CPL emission monochromator (CD/CPL hybrid system). The hybrid system measures CPL, fluorescence, CD, and absorbance on the same part of the sample without the need to move between the CD and CPL measurements. The instrument uses a xenon arc lamp as the light source, enabling a wide range of excitation wavelengths to support flexible development of new molecules and materials. Data obtained and presented for camphor, ruthenium metal complexes, the peptide gramicidin, and a DNA-ligand (4',6-diamidino-2-phenylindole, DAPI) system in this work highlight the ease of use and reproducibility of the results. The g-factors for CD and CPL obtained for the different compounds are shown to be the same for isolated transitions and some examples of how to use variations of g-factors with wavelength are demonstrated. The reliable and excellent benchmark results obtained from a custom-built commercial wavelength scanning CPL/CD hybrid instrument open up new avenues for the broader chemical and materials science community to intensify research on chiral luminescent systems.

Quantifying non-adherence to anti-tuberculosis treatment due to early discontinuation: a systematic literature review of timings to loss to follow-up.

BACKGROUND: The burden of non-adherence to anti-tuberculosis (TB) treatment is poorly understood. One type is early discontinuation, that is, stopping treatment early. Given the implications of early discontinuation for treatment outcomes, we undertook a systematic review to estimate its burden, using the timing of loss to follow-up (LFU) as a proxy measure. METHODS: Web of Science, Embase and Medline were searched up to 14 January 2021 using terms covering LFU, TB and treatment. Studies of adults (≥ 18 years) on the standard regimen for drug-sensitive TB reporting the timing of LFU (WHO definition) were included. A narrative synthesis was conducted and quality assessment undertaken using an adapted version of Downs and Black. Papers were grouped by the percentage of those who were ultimately LFU who were LFU by 2 months. Three groups were created: <28.3% LFU by 2 months, ≥28.3-<38.3%, ≥38.3%). The percentage of dose-months missed due to early discontinuation among (1) those LFU, and (2) all patients was calculated. RESULTS: We found 40 relevant studies from 21 countries. The timing of LFU was variable within and between countries. 36/40 papers (90.0%) reported the percentage of patients LFU by the end of 2 months. 31/36 studies (86.1%) reported a higher than or as expected percentage of patients becoming LFU by 2 months. The percentage of dose-months missed by patients who became LFU ranged between 37% and 77% (equivalent to 2.2-4.6 months). Among all patients, the percentage of dose-months missed ranged between 1% and 22% (equivalent to 0.1-1.3 months). CONCLUSIONS: A larger than expected percentage of patients became LFU within the first 2 months of treatment. These patients missed high percentages of dose months of treatment due to early discontinuation. Interventions to promote adherence and retain patients in care must not neglect the early months of treatment. PROSPERO REGISTRATION NUMBER: CRD42021218636.