Sexually transmitted infection diagnoses, sexualised drug use and associations with pre-exposure prophylaxis use among men who have sex with men in the UK

Previous research has focused on acceptability of pre-exposure prophylaxis (PrEP) use, but few community-based studies have been conducted regarding actual use, and PrEP use in the context of sexualised drug use remains understudied. A national online cross-sectional study recruited men who have sex with men (MSM) via social media (April–June 2018). Multivariable logistic regression was used to investigate factors associated with PrEP use. Bivariate analyses compared engaging in condomless anal intercourse (CAI) under the influence of specific drugs and recent sexually transmitted infection (STI) diagnoses (past 12 months) between MSM taking PrEP and those not. Overall, 6% (99/1581) MSM reported current PrEP use. Factors associated with PrEP use were increasing age, recent genitourinary medicine (GUM) attendance (95% versus 45%, aOR = 6.25, 95%CI 2.05, 19.03), an HIV test in the past three months (89% versus 23%, aOR = 14.22, 95%CI 6.76, 29.90), and recent engagement in chemsex (21% versus 4%, aOR = 3.56, 95%CI 1.78, 7.11). MSM taking PrEP were more likely to have had an STI diagnosis (42% versus 8%), most commonly chlamydia (26% versus 3%) and gonorrhoea (25% versus 4%). Considering the elevated levels of self-reported STI diagnoses among those on PrEP, there was a high level of engagement with sexual health services, which may help reduce onward STI transmission

Psychosocial and sexual characteristics associated with sexualised drug use and chemsex among men who have sex with men (MSM) in the UK.

OBJECTIVE: To understand how the emerging public health issue of chemsex relates to broader patterns of sexualised drug use (SDU) among men who have sex with men (MSM), which has been understudied. METHODS: Potential participants were invited to take part in an anonymous, cross-sectional online survey through Facebook advertising and community organisations' social media posts (April-June 2018). Multivariable logistic regression was used to compare MSM who engaged in recent SDU (past 12 months) with those who did not, and those who engaged in chemsex (γ-hydroxybutyrate/γ-butyrolactone, crystal methamphetamine, mephedrone, ketamine) with those who engaged in other SDU (eg, poppers, cocaine, cannabis). RESULTS: Of the 1648 MSM included, 41% reported recent SDU; 15% of these (6% of total, n=99) reported chemsex. Factors associated with SDU were recent STI diagnosis (aOR=2.44, 95% CI 1.58 to 3.76), sexual health clinic attendance (aOR=2.46, 95% CI 1.90 to 3.20), image and performance-enhancing drug use (aOR=3.82, 95% CI 1.87 to 7.82), greater number of condomless anal male partners, lower satisfaction with life and greater sexual satisfaction. Predictors of chemsex compared with other SDU were not being UK-born (aOR=2.02, 95% CI 1.05 to 3.86), living in a densely populated area (aOR=2.69, 95% CI 1.26 to 5.74), low sexual self-efficacy (aOR=4.52, 95% CI 2.18 to 9.40) and greater number of condomless anal male partners. Living with HIV, taking pre-exposure prophylaxis (PrEP), and experiencing or being unsure of experiencing sexual contact without consent were significantly associated with SDU and chemsex in bivariate analyses but not in the multivariable. CONCLUSION: Health and behavioural differences were observed between MSM engaging in chemsex, those engaging in SDU and those engaging in neither. While some MSM engaging in chemsex and SDU appeared content with these behaviours, the association with life satisfaction and sexual self-efficacy indicates psychosocial support is needed for some. The association with sexual risk and sexual consent also indicates the importance of promoting harm reduction among this population (eg, condoms, PrEP, drug knowledge)

“Belt and braces approach; added benefit and…extra reassurance”: A Multi-Stakeholder Examination of the Challenges to Effective Provision of Pre-Exposure Prophylaxis (PrEP) for HIV Prevention Among Men Who Have Sex with Men (MSM) in Northern and Central England.

Pre-exposure prophylaxis (PrEP) involves HIV negative individuals taking antiretroviral drugs to reduce the probability of infection if exposed and is available through the IMPACT trial in England. This study aimed to explore MSM and service provider (SP) perspectives on provision and accessibility of PrEP in Northern and Central England. 20 MSM and 25 SP from four Northern cities and one city in the West Midlands region were recruited for semi-structured interviews (December 2018 to October 2019). Interviews were analysed using Interpretative Phenomenological Analysis. Three key themes emerged: ‘Selfsourcing PrEP’; ‘Service delivery learnings’; and ‘Impact of using PrEP’. Problems with equity of access and accessibility were noted, and recommendations for the future of PrEP programming and equitable service delivery were also presented. The study highlighted divergence in PrEP service experience from patients and providers, with results informing policy, practice and professional training

Psychosocial and sexual factors associated with recent sexual health clinic attendance and HIV testing among trans people in the UK.

OBJECTIVES: Trans people remain an understudied population in the UK, with unmet sexual health needs. The aim of this research was to identify possible barriers and facilitators for sexual health clinic attendance and HIV testing among trans people. METHODS: Lesbian, gay, bisexual and transgender (LGBT) participants from across the UK were invited to take part in a cross-sectional online survey through Facebook advertising (April-June 2018). Psychosocial and sexual factors associated with recent sexual health clinic attendance, and ever having an HIV test were examined using multivariate logistic regression. RESULTS: A total of 3007 cisgender and 500 trans participants completed the survey. Trans participants were less likely to attend a sexual health clinic than cisgender participants (27% vs 36%, p<0.001) and report ever having an HIV test (49% vs 64%, p<0.001). One trans participant reported living with HIV and three reported currently taking pre-exposure prophylaxis. Factors associated with trans sexual health clinic attendance were: living in London, having a relationship with multiple partners, engaging in condomless anal intercourse, greater life satisfaction, and having alcohol and/or drugs before sex. Being a person of colour, aged 25-49 years, in a relationship with multiple partners, condomless anal intercourse, lower body dissatisfaction, and having drugs before sex were associated with ever having an HIV test among trans participants. CONCLUSIONS: Trans people were less likely to attend sexual health services than cisgender people, and half of trans participants who reported condomless anal intercourse had never had an HIV test. Further research is needed to understand and improve uptake of sexual health services among trans people

HIV prevalence and HIV clinical outcomes of transgender and gender-diverse people in England

Objectives: We provide the first estimate of HIV prevalence among trans and gender‐diverse people living in England and compare outcomes of people living with HIV according to gender identity. Methods: We analysed a comprehensive national HIV cohort and a nationally representative self‐reported survey of people accessing HIV care in England (Positive Voices). Gender identity was recorded using a two‐step question co‐designed with community members and civil society. Responses were validated by clinic follow‐up and/or self‐report. Population estimates were obtained from national government offices. Results: In 2017, HIV prevalence among trans and gender‐diverse people was estimated at 0.46–4.78 per 1000, compared with 1.7 (95% credible interval: 1.6–1.7) in the general population. Of 94 885 people living with diagnosed HIV in England, 178 (0.19%) identified as trans or gender‐diverse. Compared with cisgender people, trans and gender‐diverse people were more likely to be London residents (57% vs. 43%), younger (median age 42 vs. 46 years), of white ethnicity (61% vs. 52%), under psychiatric care (11% vs. 4%), to report problems with self‐care (37% vs. 13%), and to have been refused or delayed healthcare (23% vs. 11%). Antiretroviral uptake and viral suppression were high in both groups. Conclusions: HIV prevalence among trans and gender‐diverse people living in England is relatively low compared with international estimates. Furthermore, no inequalities were observed with regard to HIV care. Nevertheless, trans and gender‐diverse people with HIV report poorer mental health and higher levels of discrimination compared with cisgender people

The people living with HIV stigma survey UK 2015: HIV-related sexual rejection and other experiences of stigma and discrimination among gay and heterosexual men

We aim to understand the difference in stigma and discrimination, in particular sexual rejection, experienced between gay and heterosexual men living with HIV in the UK. The People Living with HIV StigmaSurvey UK 2015 recruited a convenience sample of persons with HIV through over 120 cross sector community organisations and 46 HIV clinics to complete an online survey. 1162 men completed the survey, 969 (83%) gay men and 193 (17%) heterosexual men, 92% were on antiretroviral therapy. Compared to heterosexual men, gay men were significantly more likely to report worrying about workplace treatment in relation to their HIV (21% vs. 11%), worrying about HIV-related sexual rejection (42% vs 21%), avoiding sex because of their HIV status (37% vs. 23%), and experiencing HIV-related sexual rejection (27% vs. 9%) in the past 12 months. In a multivariate logistic regression controlling for other sociodemographic factors, being gay was a predictor of reporting HIV-related sexual rejection in the past 12 months (aOR 2.17, CI 1.16, 4.02). Both gay and heterosexual men living with HIV experienced stigma and discrimination in the past 12 months, and this was higher for gay men in terms of HIV-related sexual rejection. Due to the high proportion of men reporting sexual rejection, greater awareness and education of the low risk of transmission of HIV among people on effective treatment is needed to reduce stigma and sexual prejudice towards people living with HIV

Murine leukemia virus RNA dimerization is coupled to transcription and splicing processes

Most of the cell biological aspects of retroviral genome dimerization remain unknown. Murine leukemia virus (MLV) constitutes a useful model to study when and where dimerization occurs within the cell. For instance, MLV produces a subgenomic RNA (called SD') that is co-packaged with the genomic RNA predominantly as FLSD' heterodimers. This SD' RNA is generated by splicing of the genomic RNA and also by direct transcription of a splice-associated retroelement of MLV (SDARE). We took advantage of these two SD' origins to study the effects of transcription and splicing events on RNA dimerization. Using genetic approaches coupled to capture of RNA heterodimer in virions, we determined heterodimerization frequencies in different cellular contexts. Several cell lines were stably established in which SD' RNA was produced by either splicing or transcription from SDARE. Moreover, SDARE was integrated into the host chromosome either concomitantly or sequentially with the genomic provirus. Our results showed that transcribed genomic and SD' RNAs preferentially formed heterodimers when their respective proviruses were integrated together. In contrast, heterodimerization was strongly affected when the two proviruses were integrated independently. Finally, dimerization was enhanced when the transcription sites were expected to be physically close. For the first time, we report that splicing and RNA dimerization appear to be coupled. Indeed, when the RNAs underwent splicing, the FLSD' dimerization reached a frequency similar to co-transcriptional heterodimerization. Altogether, our results indicate that randomness of heterodimerization increases when RNAs are co-expressed during either transcription or splicing. Our results strongly support the notion that dimerization occurs in the nucleus, at or near the transcription and splicing sites, at areas of high viral RNA concentration

Loss of Caveolin-1 Accelerates Neurodegeneration and Aging

The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease.We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression.Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease

Sharing vocabularies: towards horizontal alignment of values-driven business functions

This paper highlights the emergence of different ‘vocabularies’ that describe various values-driven business functions within large organisations and argues for improved horizontal alignment between them. We investigate two established functions that have long-standing organisational histories: Ethics and Compliance (E&C) and Corporate Social Responsibility (CSR). By drawing upon research on organisational alignment, we explain both the need for and the potential benefit of greater alignment between these values-driven functions. We then examine the structural and socio-cultural dimensions of organisational systems through which E&C and CSR horizontal alignment can be coordinated to improve synergies, address tensions, and generate insight to inform future research and practice in the field of Business and Society. The paper concludes with research questions that can inform future scholarly research and a practical model to guide organizations’ efforts towards inter-functional, horizontal alignment of values-driven organizational practice

Airway sizes and proportions in children quantified by a video-bronchoscopic technique

Background: A quantitative understanding of airway sizes and proportions and a reference point for comparisons are important to a bronchoscopist. The aims of this study were to measure large airway areas, and define proportions and predictors of airway size in children. Methods: A validated videobronchoscope technique was used to measure in-vivo airway cross-sectional areas (cricoid, right (RMS) and left (LMS) main stem and major lobar bronchi) of 125 children. Airway proportions were calculated as ratios of airways to cricoid areas and to endotracheal tube (ETT) areas. Mann Whitney U, T-tests, and one-way ANOVA were used for comparisons and standard univariate and backwards, stepwise multivariate regression analyses were used to define airway size predictors. Results: Airways size increased progressively with increasing age but proportions remained constant. The LMS was 21% smaller than the RMS. Gender differences in airways' size were not significant in any age group or airway site. Cricoid area related best to body length (BL): cricoid area (mm2) = 26.782 + 0.254*BL (cm) while the RMS and LMS area related best to weight: RMS area (mm2) = 23.938 + 0.394*Wt (kg) and LMS area (mm2) = 20.055 + 0.263*Wt (kg) respectively. Airways to cricoid ratios were larger than airway to ETT ratios (p=0.0001). Conclusions: The cricoid and large airways progressively increase in size but maintain constant proportional relationships to the cricoid across childhood. The cricoid area correlates with body length while the RMS and LMS are best predicted by weight. These data provide for quantitative comparisons of airway lesions