The structure of human argonaute-2 in complex with miR-20a.

Argonaute proteins lie at the heart of the RNA-induced silencing complex (RISC), wherein they use small RNA guides to recognize targets. Initial insight into the architecture of Argonautes came from studies of prokaryotic proteins, revealing a crescent-shaped base made up of the amino-terminal, PAZ, middle, and PIWI domains. The recently reported crystal structure of human Argonaute-2 (hAgo2), the "slicer" in RNA interference, in complex with a mixed population of RNAs derived from insect cells provides insight into the architecture of a eukaryotic Argonaute protein with defined biochemical and biological functions. Here, we report the structure of human Ago2 bound to a physiologically relevant microRNA, microRNA-20a, at 2.2 Å resolution. The miRNA is anchored at both ends by the Mid and PAZ domains and makes several kinks and turns along the binding groove. Interestingly, miRNA binding confers remarkable stability on hAgo2, locking this otherwise flexible enzyme into a stable conformation.

Correlates of concordance between self-reported and lab-confirmed viral load among Black and Latine men who have sex with men (BLMSM) living with HIV in New York City.

Sustained viral suppression is one of the four strategies in the U.S. Department of Health and Human Services' (HHS) plan to end the HIV epidemic in the United States. Individuals living with HIV must understand their viral load accurately for this strategy to be effective. We conducted cross-sectional analyses using baseline data from the NNHIV longitudinal study among men who have sex with men (MSM) living with HIV in New York City to identify factors associated with concordant knowledge between self-reported and lab-confirmed viral load. Of 164 Black and/or Latine participants, 67% (n = 110) reported that their viral load was undetectable, however lab tests showed only 44% (n = 72) had an undetectable viral load (<20 copies/ml). Overall, 62% of the sample (n = 102) had concordant HIV viral load knowledge (agreement of self-reported and lab viral load). In multivariable regression, those with unstable housing (PR = 0.52, 0.30-0.92) and those who had higher levels of beliefs of racism in medicine scale (PR = 0.76, 0.59-0.97) were less likely to have concordant knowledge. Our study underscores the need for implementing measures to improve viral load knowledge, U = U messaging, and strategies to achieve and maintain undetectable viral load status to reduce the burden of HIV at the population level.

Medical and Non-Medical Opioid Use at the Intersection of Gender and Sexual Identity: Associations with State Medical Cannabis Law Status in a U.S. National Sample of Adults.

At the structural level, medical cannabis laws (MCLs) have been negatively associated with opioid prescribing practices, and sexual minority adults report disproportionately high non-medical prescription opioid use. We examined medical/non-medical prescription opioid use by intersecting sexual identity and gender and explored associations with MCLs using the 2015-2017 National Survey on Drug Use and Health, which captured sexual identity and MCL state residence for adults 18 + years (N = 126,463). Survey-weighted gender-stratified multinomial logistic models estimated adjusted relative risk ratios (aRRR) of medical vs. no prescription opioid use, and any non-medical vs. no prescription opioid use, by sexual identity and MCL, and tested moderation by MCL. Past-year medical prescription opioid use was higher among women than men across sexual identities (e.g., bisexual: 38.5% women vs. 30.2% men). Non-medical prescription opioid use was lower among women than men, except for bisexual adults (12.4% women vs. 7.6% men). MCL was associated with lower medical prescription opioid vs. no use among heterosexual women (aRRR = 0.86, 95% confidence interval [CI] = 0.81-0.91), bisexual women (aRRR = 0.74, 95% CI = 0.62-0.89), and heterosexual men (aRRR = 0.91, 95% CI = 0.85-0.97). Living in an MCL state was associated with lower non-medical vs. no use among heterosexual and bisexual women, but not among men or lesbian/gay women. MCL status did not moderate associations between sexual identity and prescription opioid outcomes. Future studies should assess whether implementing MCLs could particularly affect bisexual women who reported the highest prescription opioid use and may need targeted services.

"It's Like Plan B but for HIV!" Design and Evaluation of a Media Campaign to Drive Demand for PEP.

Post-exposure Prophylaxis (PEP) is an effective yet underutilized HIV prevention tool. PEPTALK developed and evaluated a media campaign to drive demand for PEP among men who have sex with men (MSM) and transgender women (TW) living in high HIV prevalence areas in New York City. Formative qualitative research (38 in-depth interviews and five focus groups [N = 48]) with Black or African-American MSM or TW who reported condomless sex with a HIV-positive/unknown status man was conducted to inform campaign design. We assessed the impact of the campaign, 15 bus shelter ads and low or no-cost social media, by assessing change in the proportions of new PEP patient visits, to the clinical site where the campaign directed consumers, using one-sided z-test for proportions, before and after the media campaign. The proportion of new PEP patients increased significantly after the media campaign in the periods examined, suggesting that such campaigns may increase PEP demand.

Neighborhood and Network Characteristics and the HIV Care Continuum among Gay, Bisexual, and Other Men Who Have Sex with Men.

In order for treatment as prevention to work as a national strategy to contain the HIV/AIDS epidemic in the United States (US), the HIV care continuum must become more robust, retaining more individuals at each step. The majority of people living with HIV/AIDS (PLWHA) in the US are gay, bisexual, and other men who have sex with men (MSM). Within this population, there are distinct race- and ethnicity-based disparities in rates of HIV infection, engagement, and retention in HIV care, and viral suppression. Compared with White MSM, HIV-infected Black MSM are less likely to be on anti-retroviral therapy (ART), adhere to ART, and achieve viral suppression. Among MSM living in urban areas, falling off the continuum may be influenced by factors beyond the individual level, with new research identifying key roles for network- and neighborhood-level characteristics. To inform multi-level and multi-component interventions, particularly to support Black MSM living in urban areas, a clearer understanding of the pathways of influence among factors at various levels of the social ecology is required. Here, we review and apply the empirical literature and relevant theoretical perspectives to develop a series of potential pathways of influence that may be further evaluated. Results of research based on these pathways may provide insights into the design of interventions, urban planning efforts, and assessments of program implementation, resulting in increased retention in care, ART adherence, and viral suppression among urban-dwelling, HIV-infected MSM.

Knowledge, Stereotyped Beliefs and Attitudes Around HIV Chemoprophylaxis in Two High HIV Prevalence Neighborhoods in New York City.

HIV chemoprophylaxis (PrEP/PEP) has emerged as a transformative prevention tool to reduce infection rates and decrease disease burden. However, uptake is low, and efficacy depends upon adherence. To maximize impact, potential barriers to uptake and adherence must be identified and understood. Using univariate and logistic regression analytic methods, we assessed associations among potential barriers to uptake and adherence, including HIV chemoprophylaxis knowledge, negative stereotyped beliefs about people who use it and negative attitudes towards HIV chemoprophylaxis use by relatives among 583 residents of two high HIV prevalence neighborhoods in New York City. About a quarter of respondents knew about HIV chemoprophylaxis and over 50 % endorsed negative stereotyped beliefs about users; yet, approximately two-thirds had positive attitudes toward its use among a male or female relative. Young age, having lesbian or gay friends/family members and low levels of homophobia were associated with not endorsing negative stereotyped beliefs. Negative stereotyped beliefs were not associated with negative attitudes toward HIV chemoprophylaxis use among relatives. Implications for PrEP dissemination are discussed.

Associations Among Neighborhood Characteristics and Sexual Risk Behavior Among Black and White MSM Living in a Major Urban Area.

Identifying neighborhood characteristics associated with sexual HIV risk behavior among gay, bisexual and other men who have sex with men (MSM) living in urban areas may inform the development of policies and programs to reduce risk and subsequently HIV prevalence in urban areas. New York City M2M was a cross-sectional study designed to identify neighborhood-level characteristics associated with sexual risk behaviors among MSM living in New York City. This paper presents results of an analysis of neighborhood-level indicators of three distinct social theories of influence of the neighborhood environment on human behavior: physical disorder, social disorganization and social norms theories. Using multilevel modeling on a sample of 766 MSM stratified by race/ethnicity, we found little support for the role of social disorganization on the sexual risk behavior of MSM, whereas different indicators of physical disorder exerted negative effects across race groups. Our results suggest that the beneficial effects of housing stock maintenance and general neighborhood physical orderliness and cleanliness may have positive effects beyond those traditionally studied for African American MSM and that the field needs novel theorizing regarding whether and how neighborhood or virtual community-level factors relate to sexual behavior among MSM.

Neighborhood determinants of mood and anxiety disorders among men who have sex with men in New York City.

PURPOSE: We examined the relationship between economic, physical, and social characteristics of neighborhoods, where men who have sex with men (MSM) lived and socialized, and symptom scores of depression and generalized anxiety disorder (GAD). METHODS: Participants came from a cross-sectional study of a population-based sample of New York City MSM recruited in 2010-2012 (n = 1126). Archival and survey-based data were obtained on neighborhoods, where the men lived and where they socialized most often. RESULTS: MSM who socialized in neighborhoods with more economic deprivation and greater general neighborhood attachment experienced higher GAD symptoms. The relationship between general attachment to neighborhoods where MSM socialized and mental health depended on the level of gay community attachment: in neighborhoods characterized by greater gay community attachment, general neighborhood attachment was negatively associated with GAD symptoms, while in low gay community attachment neighborhoods, general neighborhood attachment had a positive association with GAD symptoms. CONCLUSIONS: This study illustrates the downsides of having deep ties to social neighborhoods when they occur in the absence of broader access to ties with the community of one's sexual identity. Interventions that help MSM cross the spatial boundaries of their social neighborhoods and promote integration of MSM into the broader gay community may contribute to the reduction of elevated rates of depression and anxiety in this population.

Commonalities and Differences Across Substance Use Disorders: Phenomenological and Epidemiological Aspects.

BACKGROUND: Although psychoactive substances vary in many ways, they have important commonalties, particularly in their ability to lead to an addiction syndrome. The field lacks an updated review of the commonalities and differences in the phenomenology of alcohol, cannabis, tobacco, stimulants, opioids, hallucinogens, sedatives/tranquilizers, and inhalants and their related substance use disorders (SUDs). METHODS: DSM-IV and DSM-5 SUD diagnostic criteria were reviewed, as was evidence from recent epidemiological and clinical research: psychometric studies (test-retest reliability, latent trait analysis); physiological indicators (tolerance, withdrawal); prevalence and age of onset. Information was incorporated from previous reviews, PubMed and Scopus literature searches, and data from large U.S. national surveys. RESULTS: Empirical evidence in the form of test-retest reliability and unidimensionality supports use of the same DSM-IV dependence or DSM-5 SUD diagnostic criteria across substances. For most substances, the criteria sets were generally most informative in general population samples at moderate-to-severe levels of SUD. Across substances, 2 criteria (tolerance and use in hazardous situations) were identified as functioning differently in population subgroups. Since substances have different pharmacological effects, withdrawal is assessed using substance-specific symptoms, while tolerance is not; issues remain with the assessment of tolerance. Alcohol, tobacco, and cannabis were consistently identified as the substances with earliest onset of use, highest prevalence of lifetime use, and highest prevalence of lifetime disorder. CONCLUSIONS: Despite differences between psychoactive substances, the generic DSM criteria set appears equally applicable across substances. Additional studies of tolerance and hazardous use will be useful for future nosologies. Alcohol, cannabis, and tobacco are the substances with the greatest public health impact due to the high prevalence and early onset of their use, and the potential all 3 substances have to lead to addiction.

Sexual orientation- and race-based discrimination and sexual HIV risk behavior among urban MSM.

Understanding what social factors are associated with risk of HIV acquisition and transmission among gay, bisexual and other men who have sex with men (MSM) is a critical public health goal. Experiencing discrimination may increase risk of HIV infection among MSM. This analysis assessed relations between experiences of sexual orientation- and race-based discrimination and sexual HIV risk behavior among MSM in New York City. 1,369 MSM completed a self-administered computerized assessment of past 3-month sexual behavior, experience of social discrimination and other covariates. Regression models assessed relations between recent experience of discrimination and sexual HIV risk behavior. Mean age was 32 years; 32 % were white; 32 % Latino/Hispanic; 25 % African American/Black. Of MSM who self-reported HIV-positive or unknown status (377), 7 % (N = 27) reported having unprotected insertive anal intercourse with an HIV-negative or unknown status partner ("HIV transmission risk"). Of MSM who self-reported HIV-negative status (992), 11 % (110) reported unprotected receptive anal intercourse with an HIV-positive or unknown status partner ("HIV acquisition risk"). HIV acquisition risk was positively associated with sexual orientation-based discrimination in home or social neighborhoods, but not race-based discrimination. We observed that sexual orientation-based discrimination was associated with sexual HIV risk behavior among urban-dwelling MSM. Addressing environmental sources of this form of discrimination, as well as the psychological distress that may result, should be prioritized in HIV prevention efforts.

SOCS3 is an endogenous inhibitor of pathologic angiogenesis.

Inflammatory cytokines and growth factors drive angiogenesis independently; however, their integrated role in pathologic and physiologic angiogenesis is not fully understood. Suppressor of cytokine signaling-3 (SOCS3) is an inducible negative feedback regulator of inflammation and growth factor signaling. In the present study, we show that SOCS3 curbs pathologic angiogenesis. Using a Cre/Lox system, we deleted SOCS3 in vessels and studied developmental and pathologic angiogenesis in murine models of oxygen-induced retinopathy and cancer. Conditional loss of SOCS3 leads to increased pathologic neovascularization, resulting in pronounced retinopathy and increased tumor size. In contrast, physiologic vascularization is not regulated by SOCS3. In vitro, SOCS3 knockdown increases proliferation and sprouting of endothelial cells costimulated with IGF-1 and TNFα via reduced feedback inhibition of the STAT3 and mTOR pathways. These results identify SOCS3 as a pivotal endogenous feedback inhibitor of pathologic angiogenesis and a potential therapeutic target acting at the converging crossroads of growth factor- and cytokine-induced vessel growth.

Patterns and Factors Associated With Alcohol Misuse Among Young Black Men Who Have Sex With Men in New York City.

Alcohol misuse is a significant health concern among gay, bisexual, same-gender-loving, and other men who have sex with men (MSM). Yet, little is known about the severity and predictors of alcohol misuse among self-reported young Black MSM. This study aimed to identify patterns of and factors associated with alcohol misuse in a sample of young Black MSM living in New York City. Baseline data from a randomized controlled trial aimed at improving the uptake of HIV testing among 250 MSM aged 18 to 29 were analyzed. Log-binominal regression analyses were conducted to assess the association of demographic and psychosocial factors with alcohol misuse in the past year and past 3 months among young Black MSM. Overall, 33.2% and 28.0% of young Black MSM in the study experienced alcohol misuse in the past year and past 3 months, respectively. In the adjusted model, factors positively associated with past-year alcohol misuse included marijuana use, a history of drug use, and having one-two or more than two male sex partners. Likewise, participants who used marijuana and those with one-two or more than two male partners were more likely to report past 3-month alcohol misuse. No significant association was found between positive screening for depressive symptoms, chemsex, internalized homophobia, and the likelihood of having alcohol misuse. The high prevalence of alcohol misuse underscores the importance of raising awareness of alcohol misuse and designing alcohol risk reduction programs that jointly address HIV risk among young Black MSM.

Correlates of unprotected vaginal or anal intercourse with women among substance-using men who have sex with men.

The role men who have sex with men and women (MSMW) play in heterosexual HIV transmission is not well understood. We analyzed baseline data from Project MIX, a behavioral intervention study of substance-using men who have sex with men (MSM), and identified correlates of unprotected vaginal intercourse, anal intercourse, or both with women (UVAI). Approximately 10 % (n = 194) of the men reported vaginal sex, anal sex, or both with a woman; of these substance-using MSMW, 66 % (129) reported UVAI. Among substance-using MSMW, multivariate analyses found unemployment relative to full/part-time employment (OR = 2.28; 95 % CI 1.01, 5.17), having a primary female partner relative to no primary female partner (OR = 3.44; CI 1.4, 8.46), and higher levels of treatment optimism (OR = 1.73; 95 % CI 1.18, 2.54) increased odds of UVAI. Strong feelings of connection to a same-race gay community (OR = 0.71; 95 % CI 0.56, 0.91) and Viagra use (OR = 0.31; 95 % CI 0.10, 0.95) decreased odds of UVAI. This work suggests that although the proportion of substance-using MSM who also have sex with women is low, these men engage in unprotected sex with women, particularly with primary female partners. This work highlights the need for further research with the substance using MSMW population to inform HIV prevention interventions specifically for MSMW.

"Straight Talk" for African-American heterosexual men: results of a single-arm behavioral intervention trial.

In the United States, heterosexual transmission is the second leading cause of HIV/AIDS, and two-thirds of all heterosexually acquired cases diagnosed between 2005 and 2008 occurred among African-Americans. Few HIV prevention interventions have been designed specifically for African-American heterosexual men not seeking clinical treatment. Here we report results of a single-arm intervention trial of a theory-based HIV prevention intervention designed to increase condom use, reduce concurrent partnering and increase HIV testing among heterosexually active African-American men living in high HIV prevalence areas of New York City. We tested our hypothesis using McNemar discordant pairs exact test for binary variables and paired t-tests for continuous variables. We observed statistically significant declines in mean number of total and new female partners, unprotected sex partners, and partner concurrency in both primary and nonprimary sex partnerships between baseline and 3 months postintervention.

Unexpected origins of the enhanced pairing affinity of 2'-fluoro-modified RNA.

Various chemical modifications are currently being evaluated for improving the efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene silencing in vivo. Among the 2'-ribose modifications assessed to date, 2'deoxy-2'-fluoro-RNA (2'-F-RNA) has unique properties for RNA interference (RNAi) applications. Thus, 2'-F-modified nucleotides are well tolerated in the guide (antisense) and passenger (sense) siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs. To identify potential origins of the distinct behaviors of RNA and 2'-F-RNA we carried out thermodynamic and X-ray crystallographic analyses of fully and partially 2'-F-modified RNAs. Surprisingly, we found that the increased pairing affinity of 2'-F-RNA relative to RNA is not, as commonly assumed, the result of a favorable entropic contribution ('conformational preorganization'), but instead primarily based on enthalpy. Crystal structures at high resolution and osmotic stress demonstrate that the 2'-F-RNA duplex is less hydrated than the RNA duplex. The enthalpy-driven, higher stability of the former hints at the possibility that the 2'-substituent, in addition to its important function in sculpting RNA conformation, plays an underappreciated role in modulating Watson-Crick base pairing strength and potentially π-π stacking interactions.

Age-related patterns of cocaine and methamphetamine use across the life course in the United States: Disparities by gender and sexual identity among adults.

PURPOSE: Research showing substance use decreases over the life course has focused primarily on heterosexual adults. We examined how age-related patterns of cocaine and methamphetamine use vary by sexual identity and gender among a national sample. METHODS: We included 191,954 adults aged 18-64 from the 2015-2019 National Survey on Drug Use and Health. We described the weighted prevalence of past-year cocaine and methamphetamine use and used logistic regressions to estimate relative odds of past-year cocaine and methamphetamine use by age, stratified by gender and sexual identity (heterosexual, gay/lesbian, bisexual). RESULTS: Cocaine and methamphetamine use was highest among lesbian, gay, and bisexual (LGB) adults compared to their heterosexual counterparts. Gay/lesbian men and women and bisexual men were also more likely to use cocaine at later ages. Heterosexual adults ages 26-34 (adjusted odds ratio [aOR] = 0.73; confidence interval [CI] = 0.65-0.83) were less likely than those 21-25 to report past-year cocaine use, but there were no differences between those ages 26-34 and 21-25 among any LGB sub-group. Heterosexual (aOR = 1.62; CI = 1.28-2.04) and gay (aOR = 2.93; CI = 1.26-6.80), men ages 26-34 were more likely to report past-year methamphetamine use than their counterparts ages 21-25. There were no age-related differences in past-year methamphetamine use between bisexual men and gay/lesbian women. CONCLUSIONS: Patterns of cocaine and methamphetamine use across the life course for LGB individuals differ from those of heterosexuals. This has implications for targeted prevention efforts to address stimulant use among minoritized populations.

Demographic differences in the cascade of care for unhealthy alcohol use: A cross-sectional analysis of data from the 2015-2019 National Survey on Drug Use and Health.

BACKGROUND: The screening, brief intervention, and referral to treatment (SBIRT) model is recommended by the U.S. Preventive Services Task Force to improve recognition of and intervention for unhealthy alcohol use. How SBIRT implementation differs by demographic characteristics is poorly understood. METHODS: We analyzed data from the 2015-2019 National Survey on Drug Use and Health from respondents ≥18 years old who used an outpatient clinic and had at least one alcoholic drink within the past year. Respondents were grouped into one of three mutually exclusive groups: "no binge drinking or alcohol use disorder (AUD)," "binge drinking without AUD," or "AUD." Outcome variables were likelihood of screening, brief intervention (BI), referral to treatment (RT), and AUD treatment. The demographic predictors on which outcomes were regressed included gender, age, race and ethnicity, sexual orientation, insurance status, and history of military involvement. Consistent with SBIRT guidelines, the entire sample was included in the screening model; screened persons with either binge drinking without AUD or with AUD were included in the BI model; screened persons with AUD were included in the RT model, and persons referred to treatment with AUD were included in the AUD treatment model. RESULTS: Analyses included 120,804 respondents. Women were more likely than men to be screened, but less likely to receive BI or RT. When referred to treatment, women were more likely than men to receive it. Persons aged ≥50 were least likely to be screened about alcohol, but most likely to receive BI, while persons aged 18-25 were least likely to receive BI or AUD treatment. Racial and ethnic minorities were less likely than White persons to be screened; Asians were less likely to receive RT, and Black persons were less likely to receive treatment than White persons. Persons identifying as gay, lesbian, or bisexual were equally as likely or more likely to receive SBIRT or AUD treatment as those identifying as heterosexual. Persons without insurance were less likely to be screened than those with insurance. Persons with a history of military involvement were more likely to be screened and receive BI and RT than persons who had not served in the military. CONCLUSIONS: Demographic disparities in SBIRT implementation exist. Addressing the sources of these disparities and minimizing attrition from care could improve outcomes for persons with unhealthy alcohol use.

Dual IL-6 and CTLA-4 blockade regresses pancreatic tumors in a T cell- and CXCR3-dependent manner.

This study aimed to enhance antitumor immune responses to pancreatic cancer via Ab-based blockade of IL-6 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Mice bearing s.c. or orthotopic pancreatic tumors were treated with blocking Abs to IL­6 and/or CTLA-4. In both tumor models, dual IL-6 and CTLA-4 blockade significantly inhibited tumor growth. Additional investigations revealed that dual therapy induced an overwhelming infiltration of T cells into the tumor as well as changes in CD4+ T cell subsets. Dual blockade therapy elicited CD4+ T cells to secrete increased IFN-γ in vitro. Likewise, in vitro stimulation of pancreatic tumor cells with IFN-γ profoundly increased tumor cell production of CXCR3-specific chemokines, even in the presence of IL-6. In vivo blockade of CXCR3 prevented orthotopic tumor regression in the presence of the combination treatment, demonstrating a dependence on the CXCR3 axis for antitumor efficacy. Both CD4+ and CD8+ T cells were required for the antitumor activity of this combination therapy, as their in vivo depletion via Abs impaired outcomes. These data represent the first report to our knowledge of IL-6 and CTLA­4 blockade as a means to regress pancreatic tumors with defined operative mechanisms of efficacy.

EET signaling in cancer.

Inflammation and angiogenesis in the tumor microenvironment are increasingly implicated in tumorigenesis. Endogenously produced lipid autacoids, locally acting small-molecule mediators, play a central role in inflammation and tissue homeostasis. These lipid mediators, collectively referred to as eicosanoids, have recently been implicated in cancer. Although eicosanoids, including prostaglandins and leukotrienes, are best known as products of arachidonic acid metabolism by cyclooxygenases and lipoxygenases, arachidonic acid is also a substrate for another enzymatic pathway, the cytochrome P450 (CYP) system. This eicosanoid pathway consists of two main branches: ω-hydroxylases which converts arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) and epoxygenases which converts it to four regioisomeric epoxyeicosatrienoic acids (EETs; 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET). EETs regulate inflammation and vascular tone. The bioactive EETs are produced predominantly in the endothelium and are mainly metabolized by soluble epoxide hydrolase to less active dihydroxyeicosatrienoic acids. EET signaling was originally studied in conjunction with inflammatory and cardiovascular disease. Arachidonic acid and its metabolites have recently stimulated great interest in cancer biology. To date, most research on eicosanoids in cancer has focused on the COX and LOX pathways. In contrast, the role of cytochrome P450-derived eicosanoids, such as EETs and HETEs, in cancer has received little attention. While CYP epoxygenases are expressed in human cancers and promote human cancer metastasis, the role of EETs (the direct products of CYP epoxygenases) in cancer remains poorly characterized. In this review, the emerging role of EET signaling in angiogenesis, inflammation, and cancer is discussed.

Daily cannabis use, cannabis use disorder, and any medical cannabis use among US adults: Associations within racial, ethnic, and sexual minoritized identities in a changing policy context.

Differences in cannabis use patterns among racial, ethnic and sexual minoritized identity subgroups have been attributed to marginalized identity stressors. However, associations at the intersection of these minoritized identities remain underexplored in a changing medical cannabis law (MCL) context. We estimated medical cannabis and daily cannabis use, and cannabis use disorder (CUD) by intersecting racial, ethnic and sexual minoritized identity subgroups. We included 189,800 adults in the 2015-2019 National Survey on Drug Use and Health identifying as non-Hispanic white, non-Hispanic Black, or Hispanic and self-reported heterosexual, gay/lesbian, or bisexual sexual identity. We estimated the adjusted odds of past-year: (a) any medical cannabis, (b) daily cannabis use (i.e., 300 + days/year), and (c) DSM-5-proxy CUD by sexual identity, stratified by race and ethnicity. Cannabis measures were higher among sexual minoritized groups than heterosexual adults across racial and ethnic subgroups. Bisexual adults had higher odds of any medical cannabis use than their heterosexual counterparts: non-Hispanic white (6.4% vs. 1.8%; aOR = 2.6, 95% CI = [2.5-3.5]), non-Hispanic Black (4.1% vs. 1.7%; aOR = 2.7, 95% CI = [1.6-4.5]), and Hispanic adults (5.3% vs. 1.8 %; aOR = 2.6, 95% CI = [1.9-3.3]). We found heterogeneous associations with state MCL status across subgroups stratified by race and ethnicity. Bisexual adults in MCL states had higher odds of any medical cannabis use among non-Hispanic white (aOR = 2.0, 95% CI = [1.4-2.9]) and Hispanic (aOR = 3.6, 95% CI = [1.2-10.2]) adults compared to their non-MCL counterparts, but this was marginal among non-Hispanic Black bisexual adults (aOR = 1.6, 95% CI = [1.0-2.6]). Studies should assess intended and unintended cannabis policy effects among racial, ethnic, and sexual identity subgroups.