Human induced pluripotent stem cells-derived liver organoids grown on a Biomimesys® hyaluronic acid-based hydroscaffold as a new model for studying human lipoprotein metabolism.

The liver plays a key role in the metabolism of lipoproteins, controlling both production and catabolism. To accelerate the development of new lipid-lowering therapies in humans, it is essential to have a relevant in vitro study model available. The current hepatocyte-like cells (HLCs) models derived from hiPSC can be used to model many genetically driven diseases but require further improvement to better recapitulate the complexity of liver functions. Here, we aimed to improve the maturation of HLCs using a three-dimensional (3D) approach using Biomimesys®, a hyaluronic acid-based hydroscaffold in which hiPSCs may directly form aggregates and differentiate toward a functional liver organoid model. After a 28-day differentiation 3D protocol, we showed that many hepatic genes were upregulated in the 3D model (liver organoids) in comparison with the 2D model (HLCs). Liver organoids, grown on Biomimesys®, exhibited an autonomous cell organization, were composed of different cell types and displayed enhanced cytochromes P450 activities compared to HLCs. Regarding the functional capacities of these organoids, we showed that they were able to accumulate lipids (hepatic steatosis), internalize low-density lipoprotein and secrete apolipoprotein B. Interestingly, we showed for the first time that this model was also able to produce apolipoprotein (a), the apolipoprotein (a) specific of Lp(a). This innovative hiPSC-derived liver organoid model may serve as a relevant model for studying human lipopoprotein metabolism, including Lp(a).

Prevalence of Oral Human Papillomavirus Infection Among Urban Gay, Bisexual, and Other Men Who Have Sex With Men in Canada, 2017-2019.

BACKGROUND: Oral human papillomavirus (HPV) infections are a leading cause of oropharyngeal cancers. In 2015 and 2016, HPV vaccines became publicly funded for gay, bisexual, and other men who have sex with men (GBM) under 27 years of age in most Canadian provinces. METHODS: Between 2017 and 2019, sexually-active GBM in Montreal, Toronto, and Vancouver were recruited through respondent-driven sampling. Participants aged 16 to 30 years were invited to self-collect oral rinse specimens for HPV testing. We estimated HPV prevalence in the oral tract overall and compared these by vaccination status. RESULTS: Among the 838 GBM with a valid oral specimen, 36.9% reported receiving ≥1 dose of HPV vaccine. Overall, oral HPV prevalence was 2.6% (95% confidence interval, CI: 1.5, 3.7%) for at least one HPV type and 1.2% (95% CI: 0.5, 1.9%) for any high-risk type. We detected quadrivalent (HPV 6/11/16/18) vaccine-preventable types in 0.3% (95% CI: 0.0, 1.0%) of vaccinated individuals and 1.1% (95% CI: 0.1, 2.0%) in unvaccinated individuals. CONCLUSIONS: Oral HPV prevalence was low in a population of young urban GBM in Canada of whom 37% were vaccinated. Findings serve as a benchmark for monitoring of vaccination impacts on oral HPV infection within this priority population.

Minority Stress, Psychological Distress, Sexual Compulsivity, and Avoidance-Based Motivations Associated with Methamphetamine Use Among Sexual Minority Men Living with HIV: Examining Direct and Indirect Associations Using Cross-Sectional Structural Equation Modeling.

OBJECTIVE: Sexual minority men (SMM) living with HIV report significantly greater methamphetamine use compared with heterosexual and HIV-negative peers. Greater use may be related to stressors (e.g., HIV-related stigma) faced by SMM living with HIV and subsequent psychological and behavioral sequelae. We tested an integrated theoretical model comprised of pathways between stigma, discrimination, childhood sexual abuse, psychological distress, sexual compulsivity, and cognitive escape in predicting methamphetamine use among SMM living with HIV. METHODS: Among 423 SMM living with HIV, we tested a structural equation model examining factors hypothesized to be directly and indirectly associated with methamphetamine use. Analyses were adjusted for demographic covariates and sampling bias. RESULTS: The model showed good fit (CFI = 0.96, RMSEA = 0.01). Heterosexist discrimination was associated with psychological distress (ß = 0.39, p < 0.001) and psychological distress was associated with sexual compulsivity (ß = 0.33, p < 0.001). Sexual compulsivity was associated with cognitive escape (ß = 0.31, p < 0.001), which was associated with methamphetamine use (ß = 0.51, p < 0.001). Psychological distress was associated with methamphetamine use via serial indirect effects of sexual compulsivity and cognitive escape (ß = 0.05, p < 0.05). CONCLUSIONS: Heterosexist discrimination contributed to psychological distress among SMM living with HIV. Psychological distress is linked to methamphetamine use via sexual compulsivity and cognitive avoidance. Interventions seeking to reduce the likelihood that SMM living with HIV use methamphetamine should include coping strategies specific to heterosexism and related psychological distress.

Prevalence, Determinants, and Trends in the Experience and Perpetration of Intimate Partner Violence Among a Cohort of Gay, Bisexual, and Other Men Who Have Sex with Men in Montréal, Toronto, and Vancouver, Canada (2017-2022).

Purpose: Longitudinal data on the experience and perpetration of intimate partner violence (IPV) among gay, bisexual, and other men who have sex with men (GBM) are limited. We estimated the prevalence of past 6-month (P6M) physical and/or sexual IPV (hereafter IPV) experience and perpetration, identified their determinants, and assessed temporal trends, including the impact of the coronavirus disease (COVID)-19 pandemic. Methods: We used data from the Engage Cohort Study (2017-2022) of GBM recruited using respondent-driven sampling in Montréal, Toronto, and Vancouver. Adjusted prevalence ratios (aPRs) for determinants and self-reported P6M IPV were estimated using generalized estimating equations, accounting for attrition (inverse probability of censoring weights) and relevant covariates. Longitudinal trends of IPV were also assessed. Results: Between 2017 and 2022, 1455 partnered GBM (median age 32 years, 82% gay, and 71% White) had at least one follow-up visit. At baseline, 31% of participants experienced IPV in their lifetime and 17% reported ever perpetrating IPV. During follow-up, IPV experience was more common (6%, 95% confidence interval [CI]: 5%-7%) than perpetration (4%, 95% CI: 3%-5%). Factors associated with P6M IPV experience included prior IPV experience (aPR: 2.68, 95% CI: 1.76-4.08), lower education (aPR: 2.31, 95% CI: 1.32-4.04), and substance use (injection aPR: 5.05, 95% CI: 2.54-10.05, non-injection aPR: 1.68, 95% CI: 1.00-2.82). Similar factors were associated with IPV perpetration. IPV was stable over time; periods of COVID-19 restrictions were not associated with IPV changes in this cohort. Conclusion: Prevalence of IPV was high among GBM. Determinants related to marginalization were associated with an increased risk of IPV. Interventions should address these determinants to reduce IPV and improve health.

HIV Treatment Optimism Moderates the Relationship between Sexual Risk Behavior and HIV Risk Perception among Urban HIV-negative Gay, Bisexual, and Other Men who have Sex With Men.

Using baseline data of the Engage Cohort Study, a Canadian study of sexually active gay, bisexual and other men who have sex with men (GBM), we evaluated the association between sexual behavior and risk perception among HIV-negative participants and whether HIV treatment optimism moderated this relationship. Participants were recruited by respondent-driven-sampling (RDS). We defined high-risk sexual behavior in the past six months as any condomless anal sex with a casual partner (i.e. not the participant's main partner) with either unknown HIV-status where neither used pre-exposure prophylaxis or with a partner living with HIV having detectable/unknown viral load. We assessed HIV treatment optimism-skepticism using a 12-item scale. RDS-II-weighted adjusted logistic regression models examined associations with risk perception measured by the question "How would you assess your current risk of getting HIV?" (response options were on a 6-point Likert-scale ranging from "very unlikely" to "very likely", dichotomized into "No Perceived Risk" (very unlikely/unlikely) and "Perceived Risk" (somewhat likely/likely/very likely/I think I already have HIV). Of 1961 participants, engagement in high-risk sexual behavior was reported by 155 (17.0%), 62 (12.4%), 128 (17.2%) of participants in Montréal, Toronto, and Vancouver, respectively. High-risk sexual behavior increased the odds of perceived HIV risk (pooled adjusted odds ratio = 2.9, 95%CI = 2.2-3.8). HIV treatment optimism-skepticism scores moderated the relationship: for GBM engaging in high-risk sexual behavior, higher HIV treatment optimism-skepticism scores increased perceived HIV risk. Promoting awareness around advances related to HIV prevention and treatment is important for appropriate risk assessment and for increased engagement in prevention interventions.

RESUMEN: Evaluamos la asociación entre el comportamiento sexual y la percepción de riesgo entre los participantes VIH negativos y si el optimismo sobre el tratamiento del VIH moderó esta asociación. Definimos comportamiento sexual de alto riesgo en los últimos seis meses como cualquier sexo anal sin condón con una pareja casual con un estado de VIH desconocido donde ninguno utilizó profilaxis previa a la exposición o con una pareja que vive con el VIH y que tiene una carga viral detectable/desconocida. Se evaluó el optimismo sobre el tratamiento del VIH mediante una escala de 12 ítems. Los modelos de regresión logística ajustados examinaron las asociaciones con la percepción del riesgo ("Riesgo no percibido" vs. "Riesgo percibido"). De 1961 participantes, 155 (17,0%), 62 (12,4%), 128 (17,2%) de los participantes en Montreal, Toronto y Vancouver, informaron comportamiento sexual de alto riesgo. El comportamiento sexual de alto riesgo se mostró asociado con riesgo percibido. El optimismo sobre el tratamiento modero la asociación. Promover la conciencia sobre los avances relacionados con la prevención y el tratamiento del VIH es importante para una evaluación adecuada de los riesgos y una mayor participación en las intervenciones de prevención.

Using an intersectionality-based approach to evaluate mental health services use among gay, bisexual and other men who have sex with men in Montreal, Toronto and Vancouver.

AIMS: To cope with homonegativity-generated stress, gay, bisexual and other men who have sex with men (GBM) use more mental health services (MHS) compared with heterosexual men. Most previous research on MHS among GBM uses data from largely white HIV-negative samples. Using an intersectionality-based approach, we evaluated the concomitant impact of racialization and HIV stigma on MHS use among GBM, through the mediating role of perceived discrimination (PD). METHODS: We used baseline data from 2371 GBM enrolled in the Engage cohort study, collected between 2017 and 2019, in Montreal, Toronto and Vancouver, using respondent-driven sampling. The exposure was GBM groups: Group 1 (n = 1376): white HIV-negative; Group 2 (n = 327): white living with HIV; Group 3 (n = 577): racialized as non-white HIV-negative; Group 4 (n = 91): racialized as non-white living with HIV. The mediator was interpersonal PD scores measured using the Everyday Discrimination Scale (5-item version). The outcome was MHS use (yes/no) in the prior 6 months. We fit a three-way decomposition of causal mediation effects utilizing the imputation method for natural effect models. We obtained odds ratios (ORs) for pure direct effect (PDE, unmediated effect), pure indirect effect (PIE, mediated effect), mediated interaction effect (MIE, effect due to interaction between the exposure and mediator) and total effect (TE, overall effect). Analyses controlled for age, chronic mental health condition, Canadian citizenship, being cisgender and city of enrolment. RESULTS: Mean PD scores were highest for racialized HIV-negative GBM (10.3, SD: 5.0) and lowest for white HIV-negative GBM (8.4, SD: 3.9). MHS use was highest in white GBM living with HIV (GBMHIV) (40.4%) and lowest in racialized HIV-negative GBM (26.9%). Compared with white HIV-negative GBM, white GBMHIV had higher TE (OR: 1.71; 95% CI: 1.27, 2.29) and PDE (OR: 1.68; 95% CI: 1.27, 2.24), and racialized HIV-negative GBM had higher PIE (OR: 1.09; 95% CI: 1.02, 1.17). Effects for racialized GBMHIV did not significantly differ from those of white HIV-negative GBM. MIEs across all groups were comparable. CONCLUSIONS: Higher MHS use was observed among white GBMHIV compared with white HIV-negative GBM. PD positively mediated MHS use only among racialized HIV-negative GBM. MHS may need to take into account the intersecting impact of homonegativity, racism and HIV stigma on the mental health of GBM.

Problematic alcohol use among gay, bisexual, and other men who have sex with men in Canada: the role of proximal stressors and anxiety.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBM) report high rates of problematic alcohol use, anxiety, and depression. This may, in part, be due to stressors related to their sexual identity (i.e., minority stressors). However, few studies have examined both distal and proximal stressors, as well as the specific psychological mechanisms by which these stressors may be related to alcohol use outcomes, in a representative sample of GBM. We explored the relationship between distal and proximal stressors and alcohol use outcomes, as well as the role of anxiety and depression as potential mediators of these relationships. METHODS: We analyzed the baseline data of 2,449 GBM from Engage, a cohort study of sexually active GBM recruited using respondent-driven sampling (RDS) in Montreal, Toronto, and Vancouver from February 2017 to August 2019. Using structural equation modeling, we examined the associations between distal minority stressors (i.e., experiences of heterosexist harassment, rejection, and discrimination), proximal minority stressors (i.e., internalized homonegativity, concerns about acceptance, concealment, and lack of affirmation), anxiety and depression, and alcohol consumption and alcohol use problems. RDS-adjusted analyses controlled for age, income, sexual orientation, ethnicity, recruitment city, and HIV serostatus. RESULTS: There were positive direct associations between distal stress and proximal stress, anxiety, and depression, but not alcohol use outcomes. Proximal stress had a positive direct association with anxiety, depression, and alcohol use problems, but not alcohol consumption. Anxiety was positively associated with alcohol consumption and alcohol use problems. Depression was negatively associated with alcohol consumption but not alcohol use problems. Regarding indirect effects, distal stress was associated with alcohol use outcomes via proximal stress and anxiety, but not via depression. CONCLUSIONS: We found support for a minority stress model as it relates to alcohol use outcomes among GBM. Findings suggest that proximal minority stress and anxiety differentially impact the problematic alcohol use among GBM who experience heterosexist discrimination. Clinical providers should consider incorporating the treatment of proximal minority stressors and anxiety into existing alcohol interventions for GBM.

Human Immunodeficiency Virus Treatment Attitudes and Bacterial Sexually Transmitted Infections Among Gay and Bisexual Men.

BACKGROUNDS: Positive attitudes toward human immunodeficiency virus (HIV) treatment, such as reduced concern about HIV transmissibility, are associated with sexual behaviors that may increase the risk of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM). We examined associations between HIV treatment attitudes and bacterial STI diagnoses among GBM in Canada's three largest cities. METHODS: We fit a structural equation model between HIV treatment attitudes and bacterial STI diagnoses via sexual behaviors in the Engage study's baseline data. We estimated direct and indirect paths between scores on HIV treatment attitudes and STIs via number of male anal sex partners, condomless anal sex, and oral sex. We conducted sub-analyses with participants stratified by HIV serostatus. RESULTS: Among 2449 GBM recruited in 2017 to 2019, there was a direct association between HIV treatment attitudes and current STI diagnoses (ß = 0.13; 95% CI, 0.07-0.19; P < 0.001). The mediated model revealed a positive total indirect effect through 2 pathways: (1) engaging in condomless anal sex and (2) number of male anal sex partners and condomless anal sex. These 2 indirect pathways remained in the stratified mediation models for both HIV negative GBM and for GBM living with HIV. CONCLUSIONS: The association between HIV treatment attitudes and diagnosed STIs is mediated through a higher number of male anal sex partners and condomless anal sex. The results highlight the importance of providers educating patients when providing effective STI counseling, testing, and prevention for GBM about how accurate HIV treatment attitudes may inadvertently be associated with the bacterial STI epidemic.

End of selection criteria based on sexual orientation: An international symposium on alternatives to donation deferral.

BACKGROUND AND OBJECTIVES: Until recently, gay, bisexual and other men who have sex with men (MSM) were deferred from donating blood for 3-12 months since the last male-to-male sexual contact. This MSM deferral has been discontinued by several high-income countries (HIC) that now perform gender-neutral donor selection. MATERIALS AND METHODS: An international symposium (held on 20-04-2023) gathered experts from seven HICs to (1) discuss how this paradigm shift might affect the mitigation strategies for transfusion-transmitted infections and (2) address the challenges related to gender-neutral donor selection. RESULTS: Most countries employed a similar approach for implementing a gender-neutral donor selection policy: key stakeholders were consulted; the transition was bridged by time-limited deferrals; donor compliance was monitored; and questions or remarks on anal sex and the number and/or type of sexual partners were often added. Many countries have now adopted a gender-neutral approach in which questions on pre- and post-exposure prophylaxis for human immunodeficiency virus (HIV) have been added (or retained, when already in place). Other countries used mitigation strategies, such as plasma quarantine or pathogen reduction technologies for plasma and/or platelets. CONCLUSION: The experience with gender-neutral donor selection has been largely positive among the countries covered herein and seems to be acceptable to stakeholders, donors and staff. The post-implementation surveillance data collected so far appear reassuring with regards to safety, although longer observation periods are necessary. The putative risks associated with HIV antiretrovirals should be further investigated.

Mycoplasma genitalium infection among gay, bisexual and other men who have sex with men in Montréal, Canada.

Background: The bacteria Mycoplasma genitalium has been identified as a causative agent of urethritis in men, especially in gay, bisexual and other men who have sex with men (gbMSM). Canadian clinic-based data have identified a high prevalence of M. genitalium and resistance to antibiotic treatments. This article estimates the prevalence of M. genitalium infections among Montréal gbMSM, explores correlates for M. genitalium infection and estimates the prevalence of mutations associated with antimicrobial resistance (AMR). Methods: Engage Cohort Study is a multi-site longitudinal study on sexually active gbMSM, aged 16 years and older, recruited via respondent-driven sampling in Montréal, Toronto and Vancouver. Participants completed a questionnaire on behaviour and were tested for sexually transmitted and blood-borne infections at each visit. For this sub-study, Montréal participants with a follow-up visit that occurred between November 2018 and November 2019 were included. Results: A total of 2,064 samples were provided by 716 participants. Prevalence of M. genitalium infection was 5.7% at rectal and/or urethral sites, 4.0% at rectal site and 2.2% at urethral site. Correlates for M. genitalium infection were younger age and reporting six or more sexual partners in the past six months. Prevalence of macrolide resistance associated mutations (MRAM), quinolone resistance associated mutations (QRAM) and either MRAM or QRAM, was 82%, 29% and 85%, respectively. Conclusion: This first population-based study among gbMSM in Canada documents a high prevalence of urethral and rectal M. genitalium infection and high levels of AMR. Our results highlight the importance of access to testing and AMR detection when indicated.

Lipoprotein(a): A Residual Cardiovascular Risk Factor in Statin-Treated Stroke Survivors: Insights From the SPARCL Trial.

Background: In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol levels) trial, atorvastatin (80 mg/d) was compared to placebo in patients with recent stroke or transient ischemic attack (TIA) and no known coronary artery disease. Objectives: This study aimed to assess the contribution of lipoprotein(a) [Lp(a)] to subsequent cerebrovascular and cardiovascular events in stroke/TIA survivors. Methods: Lp(a) levels and apolipoprotein(a) [apo(a)] isoform size were determined by liquid-chromatography mass spectrometry in samples collected at baseline from 2,814 SPARCL participants (1,418 randomized to atorvastatin and 1,396 to placebo). Within each treatment arm, patients in the highest quartile (≥84.0 nmol/L) were compared with those in the lowest quartiles of Lp(a) concentrations. Patients in the lowest quartile (≤25.9 Kringle IV domains) of apo(a) isoform sizes were compared with those in the highest quartiles. Multivariable-adjusted HRs were calculated using Cox proportional regression models. Results: There was no significant association between Lp(a) concentrations or apo(a) isoform sizes and the risk of recurrent stroke, the primary outcome of SPARCL, or cerebrovascular events in patients randomized to atorvastatin or placebo. In contrast, in patients randomized to atorvastatin, elevated Lp(a) concentrations and short apo(a) isoforms were positively and independently associated with an increased risk of coronary events (HR: 1.607 [95% CI: 1.007-2.563] and HR: 2.052 [95% CI: 1.303-3.232]). No such association was found in patients randomized to placebo (HR: 1.025 [95% CI: 0.675-1.555] and HR: 1.097 [95% CI: 0.735-1.637]). Conclusions: Lp(a) contributes to the residual coronary artery disease risk of statin-treated stroke/TIA survivors, paving the way for use of therapies targeting Lp(a) in this population with stroke. (Lipitor In The Prevention Of Stroke, For Patients Who Have Had A Previous Stroke [SPARCL]; NCT00147602).