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Abstract Background The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring. Methods Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. Results We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials. Conclusions RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.

Abstract Clinical studies have confirmed that renal oncocytoma (RO) is a benign neoplasm with excellent prognosis. In diagnostically challenging cases of renal oncocytic epithelial neoplasms, fluorescent in-situ hybridization (FISH) is increasingly being used and its ability to distinguish RO from chromophobe renal cell carcinoma (ChRCC) has been documented. In this study, we evaluated the differential diagnostic contribution of FISH in cases of RO. Clinicopathologic data and glass slides from 73 patients with RO were reviewed; 20 cases of ChRCC were included for comparison. FISH analysis of formalin-fixed, paraffin-embedded sections was performed using centromeric probes for chromosomes 1, 2, 7 and 17. FISH analysis revealed ROs had frequent loss of signal for chromosome 1 (56%) and 17 (44%). Tumors with more than one loss were common (41%) and 10% cases showed loss of all chromosomes examined. A total of 18% cases did not show any abnormality. Our study shows that chromosomal abnormalities in both ROs and ChRCCs are common with frequent loss of chromosomes 1 and 17. No association was found between overall patient survival and the extent of chromosomal abnormalities. FISH results, even those showing significant chromosomal abnormalities, should not alter the primarily morphology-based diagnosis of RO.

Objectives: The global mpox (clade II) outbreak of 2022 primarily affected gay, bisexual, and other men who have sex with men (GBM) and was met with swift community and public health responses. We aimed to estimate the relative impact of changes in sexual behaviours, contact tracing/isolation, and first-dose vaccination on transmission in Canadian cities., Methods: We estimated changes in sexual behaviours during the outbreak using 2022 data from the Engage Cohort Study which recruited self-identified GBM in Montréal, Toronto, and Vancouver (n=1,445). We developed a transmission dynamic model to estimate the averted fraction of new infections attributable to the three interventions in each city., Results: The empirical estimates of sexual behaviours changes were imprecise: 20% (RR=0.80; 95% credible intervals [95%CrI]: 0.47-1.36) fewer sexual partners in the past 6 months among those reporting ≤7 partners and 33% (RR=0.67; 95%CrI: 0.31-1.43) fewer among those with >7 partners. The three interventions combined averted 46%-58% of cases. Reductions in sexual partners, contact tracing/isolation prevented approximately 12% and 14% of cases, respectively. Vaccination's effect varied across cities by start date and coverage, with 21%-39% mpox infections prevented., Conclusions: Reduction in sexual activity, contact tracing/isolation, and vaccination all contributed to accelerating epidemic control. Early vaccination had the largest impact., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph Cox reports research grants from Gilead Sciences Canada and ViiV Healthcare, all outside of the submitted work. Mathieu Maheu-Giroux reports contractual arrangements from the World Health Organization, the Joint United Nations Programme on HIV/AIDS (UNAIDS), and the Public Health Agency of Canada, all outside of the submitted work. Trevor A. Hart reports educational grants from being an Advisory Committee member for the Canadian Institutes of Health Research (CIHR)’s Institute of Infection and Immunity and funds for community engagement events from ViiV Healthcare and Gilead Sciences Canada, all outside of the submitted work. Darrell H.S. Tan's institution has received investigator-initiated grants from Abbvie and Gilead, and support for participation in clinical trials sponsored by Glaxo Smith Kline, all outside of the submitted work. All other authors report no conflict of interest., (Copyright © 2025. Published by Elsevier Ltd.)

Δ 9 -tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, acts in the brain primarily via cannabinoid CB1 receptors. These receptors are implicated in several forms of synaptic plasticity - depolarization-induced suppression of excitation (DSE), metabotropic suppression of excitation (MSE), long term depression (LTD) and activation-dependent desensitization. Cultured autaptic hippocampal neurons express all of these, illustrating the rich functional and temporal heterogeneity of CB1 at a single set of synapses. Here we report that coincident activation of muscarinic acetylcholine receptors and elicitation of DSE in autaptic hippocampal neurons results in a substantial (∼40 %) and temporally precise inhibition of excitatory transmission lasting ∼10 minutes. Its induction is blocked by CB1 and muscarinic M3/M5 receptor antagonists and is absent in CB1 receptor knockout neurons. Notably, once it is established, inhibition is reversed by a CB1, but not a muscarinic, antagonist, suggesting that the inhibition occurs via persistent activation of CB1 receptors. We refer to this inhibition as muscarinic cannabinoid suppression of excitation (MCSE). MCSE can be mimicked by coapplication of muscarinic and cannabinoid agonists and requires Ca 2+ -release from internal stores. As such, MCSE represents a novel and targeted form of coincidence detection - important for many modes of learning and memory -- between cannabinoid and muscarinic signaling systems that elicits a medium-duration depression of synaptic signaling. Given the known roles of muscarinic and cannabinoid receptors in the hippocampus, MCSE may be important in the modulation of hippocampal signaling at the site of septal inputs, with potential implications for learning and memory, epilepsy and addiction., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus responsible for severe infections of the central nervous system. Although neurons are predominantly targeted, specific involvement of microglia in pathogenesis of TBE is not yet fully understood. In this study, the susceptibility of human microglia to TBEV is investigated, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudörfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. In particular, immune response varied significantly with the viral strain, as shown by the differential secretion of cytokines and chemokines such as IP-10, MCP-1, IL-8 and IL-6, quantified using a Luminex 48-plex assay. The most virulent strain triggered the highest cytokine induction. Electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology and contribute to a deeper understanding of TBE pathogenesis and neuroinflammation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aims: To determine the incidence of children < 2 years old with suspected abusive head trauma, to evaluate usage of dedicated skeletal radiographs and the incidence of clinically occult fractures on dedicated skeletal radiographs., Methods: This is a retrospective single centre study of children < 2 years old with traumatic brain injury, referred to the University Hospital's Social Services Department between December 31, 2012 and December 31, 2020. Clinical and demographic data was retrieved from medical notes and imaging was reviewed by paediatric radiologists., Results: 26 children (17 males), 2 weeks to 21 months of age (median age 3 months) were included. Eleven children (42%) had traumatic history, fourteen children (54%) had one or more bruises, eighteen children (69%) had abnormal neurological findings. 16 children (62%) had dedicated skeletal radiographs, 7 children (27%) had radiographs of part of the skeleton and 3 children (11%) had no skeletal radiographs. 5 out of 16 children (31%) with dedicated skeletal radiographs had a clinically occult fracture. 15 (83%) of clinically occult fractures had high specificity for abuse., Conclusion: The incidence of suspected abusive head trauma in children < 2 years old is low. Clinically occult fractures were detected in one third of children with dedicated skeletal radiographs. The majority of these fractures have high specificity for abuse. Dedicated skeletal imaging is not performed in more than one third of the children and hence fractures may be missed. Efforts should be taken to increase awareness of child abuse imaging protocols., Competing Interests: The authors report no conflicts of interest in this work.

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

2-Arachidonoyl glycerol (2-AG) is the principal endogenously produced ligand for the cannabinoid CB1 and CB2 receptors (CBRs). The lack of potent and efficacious 2-AG ligands with resistance against metabolizing enzymes represents a significant void in the armamentarium of research tools available for studying eCB system molecular constituents and their function. Herein we report the first endocannabinoid glyceride templates with remarkably high potency and efficacy at CBRs. Two of our lead chiral 2-AG analogs, namely, (13 S )- and (13 R )-Me-2-AGs, potently inhibit excitatory neurotransmission via CB1 while they are endowed with excellent resistance to the oxidizing enzyme COX-2. Our SAR results are supported by docking studies of the key analog and 2-AG on the crystal structures of CB1., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Ethnopharmacological Relevance: Ferns form an important part of the human diet. Young fern fiddleheads are mostly consumed as vegetables, while the rhizomes are often extracted for starch. These edible ferns are also often employed in traditional medicine, where all parts of the plant are used, mostly to prepare extracts. These extracts are applied either externally as lotions and baths or internally as potions, decoctions and teas. Ailments traditionally treated with ferns include coughs, colds, fevers, pain, burns and wounds, asthma, rheumatism, diarrhoea, or skin diseases (eczema, rashes, itching, leprosy)., Aim of the Review: This review aims to compile the worldwide knowledge on the traditional medicinal uses of edible fern species correlating to reported biological activities and isolated bioactive compounds., Materials and Methods: The articles and books published on edible fern species were searched through the online databases Web of Science, Pubmed and Google Scholar, with critical evaluation of the hits. The time period up to the end of 2022 was included., Results: First, the edible fern species were identified based on the literature data. A total of 90 fern species were identified that are eaten around the world and are also used in traditional medicine. Ailments treated are often associated with inflammation or bacterial infection. However, only the most common and well-known fern species, were investigated for their biological activity. The most studied species are Blechnum orientale L., Cibotium barometz (L.) J. Sm., Diplazium esculentum (Retz.) Sw., Marsilea minuta L., Osmunda japonica Thunb., Polypodium vulgare L., and Stenochlaena palustris (Burm.) Bedd. Most of the fern extracts have been studied for their antioxidant, anti-inflammatory and antimicrobial activities. Not surprisingly, antioxidant capacity has been the most studied, with results reported for 28 edible fern species. Ferns have been found to be very rich sources of flavonoids, polyphenols, polyunsaturated fatty acids, carotenoids, terpenoids and steroids and most of these compounds are remarkable free radical scavengers responsible for the outstanding antioxidant capacity of fern extracts. As far as clinical trials are concerned, extracts from only three edible fern species have been evaluated., Conclusions: The extracts of edible fern species exert antioxidant anti-inflammatory and related biological activities, which is consistent with their traditional medicinal use in the treatment of wounds, burns, colds, coughs, skin diseases and intestinal diseases. However, studies to prove pharmacological activities are scarce, and require chemical-biological standardization. Furthermore, correct botanical classification needs to be included in publications to simplify data acquisition. Finally, more in-depth phytochemical studies, allowing the linking of traditional use to pharmacological relevance are needed to be done in a standardized way., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The 2022-2023 global mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM). We investigated differences in GBM's sexual partner distributions across Canada's 3 largest cities and over time, and how they shaped transmission., Methods: The Engage Cohort Study (2017-2023) recruited GBM via respondent-driven sampling in Montréal, Toronto, and Vancouver (n = 2449). We compared reported sexual partner distributions across cities and periods: before COVID-19 (2017-2019), pandemic (2020-2021), and after lifting of restrictions (2021-2023). We used Bayesian regression and poststratification to model partner distributions. We estimated mpox's basic reproduction number (R0) using a risk-stratified compartmental model., Results: Pre-COVID-19 pandemic distributions were comparable: fitted average partners (past 6 months) were 10.4 (95% credible interval: 9.4-11.5) in Montréal, 13.1 (11.3-15.1) in Toronto, and 10.7 (9.5-12.1) in Vancouver. Sexual activity decreased during the pandemic and increased after lifting of restrictions, but remained below prepandemic levels. Based on reported cases, we estimated R0 of 2.4 to 2.7 and similar cumulative incidences (0.7%-0.9%) across cities., Conclusions: Similar sexual partner distributions may explain comparable R0 and cumulative incidence across cities. With potential for further recovery in sexual activity, mpox vaccination and surveillance strategies should be maintained., Competing Interests: Potential conflicts of interest. J. C. reports investigator-sponsored research grants from Gilead Sciences Canada and ViiV Healthcare, all outside of the submitted work. M. M.-G. reports an investigator-sponsored research grant from Gilead Sciences, Inc; and contractual arrangements from the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS), all outside of the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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 (β = 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., Competing Interests: Conflict of Interest and Sources of Funding: The Engage Cohort Study is led by Principal Investigators in Toronto by T.A.H. and D.G., in Montreal by J.C. and G.L., and in Vancouver by Jody Jollimore, Nathan Lachowsky, and David Moore. The authors would like to thank the Engage/Momentum II study participants, office staff, and community engagement committee members, as well as our community partner agencies. Engage/Momentum II is funded by the Canadian Institutes for Health Research (CIHR, TE2-138299; FDN=143342; PJT-153139), the Canadian Foundation for AIDS Research (CANFAR), the Ontario HIV Treatment Network (OHTN, 1051), the Public Health Agency of Canada (4500345082), and Toronto Metropolitan University. T.A.H. was supported by an Endgame Leader Chair Award in Gay and Bisexual Men's Health from the Ontario HIV Treatment Network. D.M.M. and N.J.L. are supported by Scholar Awards from the Michael Smith Foundation for Health Research (5209, 16863). S.S.-S. is supported by a CIHR postdoctoral fellowship award. D.G. is supported by a Canada Research Chair in Sexual and Gender Minority Health. D.H.S.T. is supported by a Tier 2 Canada Research Chair in HIV Prevention and STI Research. J.M.S. was supported by a CTN postdoctoral fellowship award. The authors would like to thank the participants and staff of the Engage Cohort Study and our community engagement committees and community partner organizations., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

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., (© 2024. The Author(s).)

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 ( β  = 0.39, p  < 0.001) and psychological distress was associated with sexual compulsivity ( β  = 0.33, p  < 0.001). Sexual compulsivity was associated with cognitive escape ( β  = 0.31, p  < 0.001), which was associated with methamphetamine use ( β  = 0.51, p  < 0.001). Psychological distress was associated with methamphetamine use via serial indirect effects of sexual compulsivity and cognitive escape ( β  = 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.

The 2022 mpox outbreak predominantly impacted gay, bisexual, and other men who have sex with men (gbMSM). Two models were developed to support situational awareness and management decisions in Canada. A compartmental model characterized epidemic drivers at national/provincial levels, while an agent-based model (ABM) assessed municipal-level impacts of vaccination. The models were parameterized and calibrated using empirical case and vaccination data between 2022 and 2023. The compartmental model explored: (1) the epidemic trajectory through community transmission, (2) the potential for transmission among non-gbMSM, and (3) impacts of vaccination and the proportion of gbMSM contributing to disease transmission. The ABM incorporated sexual-contact data and modeled: (1) effects of vaccine uptake on disease dynamics, and (2) impacts of case importation on outbreak resurgence. The calibrated, compartmental model followed the trajectory of the epidemic, which peaked in July 2022, and died out in December 2022. Most cases occurred among gbMSM, and epidemic trajectories were not consistent with sustained transmission among non-gbMSM. The ABM suggested that unprioritized vaccination strategies could increase the outbreak size by 47%, and that consistent importation (≥5 cases per 10 000) is necessary for outbreak resurgence. These models can inform time-sensitive situational awareness and policy decisions for similar future outbreaks., (© 2023 His Majesty the King in Right of Canada and The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. Reproduced with the permission of the Minister of Health.)

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., Competing Interests: Competing interests J Cox and G Lambert report non-financial support from the Direction régionale de santé publique, Centre intégré universitaire de santé et de services sociaux du Centre-Sud-de-l’Île-de-Montréal. J Cox reports grants and personal fees from ViiV Healthcare and Gilead Sciences Canada, and personal fees from Merck Canada, outside the submitted work. DM Moore reports a grant from the Michael Smith Foundation for Health Research. No other competing interests were declared.

Diabetes mellitus (DM) is a very serious disease, the incidence of which has been increasing worldwide. The beginning of diabetic research can be traced back to the 17th century. Since then, animals have been experimented on for diabetic research. However, the greatest development of diabetes research occurred in the second half of the last century, along with the development of laboratory techniques. Information obtained by monitoring patients and animal models led to the finding that there are several types of DM that differ significantly from each other in the causes of the onset and course of the disease. Through different types of animal models, researchers have studied the pathophysiology of all types of diabetic conditions and discovered suitable methods for therapy. Interestingly, despite the unquestionable success in understanding DM through animal models, we did not fully succeed in transferring the data obtained from animal models to human clinical research. On the contrary, we have observed that the chances of drug failure in human clinical trials are very high. In this review, we will summarize the history and presence of animal models in the research of DM over the last hundred years. Furthermore, we have summarized the new methodological approaches, such as "organ-on-chip," that have the potential to screen the newly discovered drugs for human clinical trials and advance the level of knowledge about diabetes, as well as its therapy, towards a personalized approach.

Autaptic hippocampal neurons are an architecturally simple model of neurotransmission that express several forms of cannabinoid signaling. Over the past twenty years this model has proven valuable for studies ranging from enzymatic control of endocannabinoid production and breakdown, to CB 1 receptor structure/function, to CB 2 signaling, understanding 'spice' (synthetic cannabinoid) pharmacology, and more. However, while studying cannabinoid signaling in these neurons, we have occasionally encountered what one might call 'interesting negatives', valid and informative findings in the context of our experimental design that, given the nature of scientific publishing, may not otherwise find their way into the scientific literature. In autaptic hippocampal neurons we have found that: (1) The fatty acid binding protein (FABP) blocker SBFI-26 does not alter CB1-mediated neuroplasticity. (2) 1-AG signals poorly relative to 2-AG in autaptic neurons. (3) Indomethacin is not a CB1 PAM in autaptic neurons. (4) The CB1-associated protein SGIP1a is not necessary for CB1 desensitization. We are presenting these negative or perplexing findings in the hope that they will prove beneficial to other laboratories and elicit fruitful discussions regarding their relevance and significance., (© 2023. The Author(s).)

Background: Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects., Material and Methods: We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed., Results: Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function ( p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI., Conclusions: In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.

Neuropeptide B (NPB) and neuropeptide W (NPW) are neuropeptides, which constitute NPB/W signaling systems together with G-protein coupled receptors NPBWR1. The location and function of NPB/W signaling systems have been predominantly detected and mapped within the CNS, including their role in the modulation of inflammatory pain, neuroendocrine functions, and autonomic nervous systems. The aim of the study is to investigate the impact of diabetes on the neuropeptide B/W signaling system in different heart compartments and neurons which innervates it. In the RT-qPCR analysis, we observed the upregulation of mRNA for preproNPB in RV, for preproNPW in LA, and for NPBWR1 in DRG in diabetic rats. On the contrary, the expression of mRNA for NPBWR1 was downregulated in LV in diabetic rats. In the WB analysis, significant downregulation of NPBWR1 in LV (0.54-fold, p = 0.046) in diabetic rats was observed at the proteomic level. The presence of NPBWR1 was also confirmed in a dissected LCM section of cardiomyocytes and coronary arteries. The positive inotropic effect of NPW described on the diabetic cardiomyocytes in vitro could point to a possible therapeutic target for compensation of the contractile dysfunction in the diabetic heart. In conclusion, the NPB/W signaling system is involved in the regulation of heart functions and long-term diabetes leads to changes in the expression of individual members of this signaling system differently in each cardiac compartment, which is related to the different morphology and function of these cardiac chambers.

Background: An individualized behavior-based selection approach has potential to allow for a more equitable blood donor eligibility process. We collected biological and behavioral data from urban gay, bisexual, and other men who have sex with men (GBM) to inform the use of this approach in Canada., Study Design and Methods: Engage is a closed prospective cohort of sexually active GBM, aged 16+ years, recruited via respondent-driven-sampling (RDS) in Montreal, Toronto, and Vancouver, Canada. Participants completed a questionnaire on behaviors (past 6 months) and tested for HIV and sexually transmitted and blood-borne infections at each visit. Rate ratios for HIV infection and predictive values for blood donation eligibility criteria were estimated by RDS-adjusted Poisson regression., Results: Data on 2008 (study visits 2017-02 to 2021-08) HIV-negative participants were used. The HIV incidence rate for the three cities was 0.4|100 person-years [95%CI:0.3, 0.6]. HIV seroconversion was associated with age <30 years: adjusted rate ratio (aRR) 9.1 [95%CI:3.2, 26.2], 6-10 and >10 anal sex partners versus 1-6 aRR: 5.3 [2.1,13.5] and 8.4 [3.4, 20.9], and use of crystal methamphetamine during sex: 4.2 [1.5, 11.6]. Applying the combined selection criteria: drug injection, ≥2 anal sex partners, and a new anal sex partner, detected all participants who seroconverted (100% sensitivity, 100% negative predictive value), and would defer 63% of study participants from donating., Conclusion: Using three screening questions regarding drug injection and sexual behaviors in the past 6 months would correctly identify potential GBM donors at high risk of having recently contracted HIV. Doing so would reduce the proportion of deferred sexually active GBM by one-third., (© 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Indoor air is typically a mixture of many chemicals at low concentrations without any adverse health effects alone, but in mixtures they may cause toxicity and risks to human health. The aim of this study was by using new approach methods to assess the potential toxicity of indoor air condensates. In specific, different in vitro test methods including cyto-and immunotoxicity, skin sensitization and endocrine disruption were applied. In addition to biological effects, the indoor air samples were subjected to targeted analysis of 25 volatile organic compounds (VOCs) and Genapol X-80 (a nonionic emulsifier) suspected to be present in the samples, and to a non-targeted "total chemical scan" to find out whether the chemical composition of the samples is associated with the biological effects. The results confirm that assessing health risks of indoor air by analysing individual chemicals is not an adequate approach: We were not able to detect the VOCs and Genapol X-80 in the indoor air samples, yet, several types of toxicity, namely, cytotoxicity, immunotoxicity, skin sensitization and endocrine disruption were detected. In the non-targeted total chemical scan of the indoor air samples, a larger number of compounds were found in the cytotoxic samples than in the non-cytotoxic samples supporting the biological findings. If only one biological method would be selected for the screening of indoor air quality, THP-1 macrophage/WST-1 assay would best fit for the purpose as it is sensitive and serves as a good representative for different sub-toxic end points, including immunotoxicity, (skin) sensitization and endocrine disruption., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)