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1.
Nat Commun ; 15(1): 5809, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987584

RESUMO

Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. In contrast, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and TAZ knockdown reduced proliferation, migration and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote carcinogenesis by different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration and invasion in HPV18+ cancers.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proliferação de Células , Via de Sinalização Hippo , Papillomavirus Humano 18 , Infecções por Papillomavirus , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Fatores de Transcrição , Neoplasias do Colo do Útero , Proteínas de Sinalização YAP , Humanos , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Sinalização YAP/metabolismo , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Transativadores/metabolismo , Transativadores/genética , Carcinogênese/genética
2.
Drug Alcohol Depend ; 261: 111356, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38889573

RESUMO

INTRODUCTION: Young adults who are sexual and gender minorities (SGM) are at the highest risk for tobacco initiation in young adulthood. Minority stress theory suggests that sexual orientation and gender identity (SOGI)-based discrimination may contribute to nicotine and tobacco use disparities. Our study aimed to quantify the association between SOGI-based distal minority stressors and current tobacco use among SGM young adults living in the United States (US). METHODS: Eligible participants-including young adults (aged 18-35 years old), who identified as SGM, and were currently residing in the US (N=1116) -were recruited via Prolific into an online survey. We applied stepwise binary regressions with backward selection to model the association between average past 30-day distal minority stress and current tobacco use (i.e., combustible cigarettes or e-cigarettes), controlling for perceived stress and sociodemographic covariates. We also tested interactions between minority stress and SGM status. Exploratory analyses assessed associations between minority stress and current tobacco use among YA, stratified by SGM subgroup. RESULTS: A 1-unit increase in experiencing minority stress in the past 30-days was associated with 1.02 greater odds of current tobacco use among SGM young adults. No difference between SGM subgroups in this association was found. Examining stratified SGM subgroups, a 1-unit increase in minority stress was associated with 1.11 greater odds of current tobacco among transgender adults only. CONCLUSION: Distal minority stress is differentially associated with current tobacco use for transgender young adults, which suggests that tobacco prevention and cessation interventions may need tailoring for subgroups. IMPLICATIONS: This study details the influence of minority stress on current tobacco use among sexual and gender minority (SGM) young adults. Findings underscore the need for targeted and tailored approaches to tobacco control, wherein SGM young adults most at-risk are engaged in cessation interventions that address minority stress as a contributing factor to tobacco use and which support their resilience. To promote health equity, tobacco control must address the contexts that engender minority stress. Assessment of policy impacts on SGM tobacco use and the effectiveness of interventions disseminated within SGM-supportive and discriminatory policy environments are important next steps.


Assuntos
Minorias Sexuais e de Gênero , Estresse Psicológico , Uso de Tabaco , Humanos , Masculino , Adulto Jovem , Minorias Sexuais e de Gênero/psicologia , Feminino , Adulto , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Adolescente , Uso de Tabaco/epidemiologia , Estados Unidos/epidemiologia , Grupos Minoritários
3.
Arch Suicide Res ; : 1-15, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38853399

RESUMO

OBJECTIVE: Transgender and gender diverse (TGD) populations have a higher prevalence of suicide outcomes compared to cisgender peers. Further, among TGD groups, young adults frequently demonstrate a higher risk compared to other age cohorts. While evidence supports sociodemographic differences in suicide risk, these relationships are not well-established for TGD young adults. METHOD: A secondary data analysis of the young adult (18-24 years) subpopulation of the 2015 U.S. Transgender Survey was conducted. Predicted probabilities of 12-month and lifetime suicide outcomes by gender identity, sexual orientation, race/ethnicity, homelessness, and poverty were estimated comparing fully adjusted models. RESULTS: Gender identity, race/ethnicity, and homelessness were significantly associated with all suicide outcomes. Comparisons of gender identities were significant for all outcomes and varied based on the outcome. American Indian/Alaska Native TGD young adults had the highest predicted probabilities compared to other race/ethnicity groups. Further, having a heterosexual/straight sexual identity was among the lowest predicted probabilities for suicide outcomes and significantly differed from several of the other sexual identities. CONCLUSIONS: Findings underscore the importance of heterogeneity among TGD young adults and the need for intersectional research within this population. Elucidating sociodemographic characteristics that contribute to differential suicide risk is necessary for effective intervention strategies and policy advocacy.

4.
mSphere ; 9(6): e0013124, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38747609

RESUMO

Ethan L. Morgan works on human papillomaviruses (HPVs), with a specific interest in identifying how HPV induces tumor formation. In this mSphere of Influence article, he reflects on how three papers influenced him. "Comprehensive genomic characterization of head and neck squamous cell carcinomas" (The Cancer Genome Atlas Network, Nature 517:576-582, 2015, https://doi.org/10.1038/nature14129) and "Integrated genomic and molecular characterization of cervical cancer" (The Cancer Genome Atlas Network, Nature 543: 378-384, 2017, https://doi.org/10.1038/nature21386) showed him the power behind comprehensive multi-omic analyses to understand disease biology, while "Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response" (J. Sitz et al., Proc Natl Acad Sci U S A 116:19552-19562, 2019, https://doi.org/10.1073/pnas.1906102116) reinforced how this can be used to undercover potential new drug targets in HPV-associated disease.


Assuntos
Genômica , Humanos , Infecções por Papillomavirus/virologia , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Multiômica
5.
Oncogene ; 43(28): 2184-2198, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38789663

RESUMO

Human papillomaviruses (HPV) are a major cause of malignancy, contributing to ~5% of all human cancers worldwide, including most cervical cancer cases and a growing number of anogenital and oral cancers. The major HPV viral oncogenes, E6 and E7, manipulate many host cellular pathways that promote cell proliferation and survival, predisposing infected cells to malignant transformation. Despite the availability of highly effective vaccines, there are still no specific anti-viral therapies targeting HPV or treatments for HPV-associated cancers. As such, a better understanding of viral-host interactions may allow the identification of novel therapeutic targets. Here, we demonstrate that the actin-binding protein LASP1 is upregulated in cervical cancer and significantly correlates with a poorer overall survival. In HPV positive cervical cancer, LASP1 depletion significantly inhibited the oncogenic phenotype in vitro, whilst having minimal effects in HPV negative cervical cancer cells. Furthermore, we demonstrate that the LASP1 SH3 domain is essential for LASP1-mediated oncogenicity in these cells. Mechanistically, we show that HPV E7 regulates LASP1 at the post-transcriptional level by repressing the expression of miR-203, which negatively regulates LASP1 mRNA levels by binding to its 3'UTR. Finally, we demonstrate that LASP1 expression is required for the growth of HPV positive cervical cancer cells in an in vivo tumourigenicity model. Together, these data demonstrate that HPV induces LASP1 expression to promote proliferation and survival in cervical cancer, thus identifying a potential therapeutic target in these cancers.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proliferação de Células , Proteínas do Citoesqueleto , Proteínas com Domínio LIM , MicroRNAs , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , MicroRNAs/genética , Humanos , Feminino , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proliferação de Células/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Animais , Camundongos , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
6.
AIDS Care ; 36(5): 682-691, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38451740

RESUMO

Although pre-exposure prophylaxis (PrEP) is a highly effective preventive treatment for HIV, anticipated PrEP stigma can hinder uptake. Perceptions of bias in HIV prevention and evaluations (e.g., happiness) tied to social support among Black and Latine/x sexual and gender diverse (SGD) individuals could be important correlates of anticipated PrEP stigma. To further this line of inquiry, a national sample of 872 Black and Latine/x SGD individuals who had and had never taken PrEP (Mage = 25.1, SD = 2.8) reported how they perceived HIV prevention and how happy they were with their social support. Multivariable linear regressions revealed that greater perceptions of bias in HIV prevention services were associated with higher anticipated PrEP stigma among Black and Latine/x SGD individuals who have never taken PrEP. Greater happiness with friend support was associated with lower PrEP stigma, whereas greater happiness with family support was associated with higher PrEP stigma among individuals who have taken PrEP. Findings highlight the need for PrEP and HIV interventions to address the intersectional stigma attached to prevention and for researchers to understand how evaluations of social support may contribute to stigma among Black and Latine/x SGD individuals.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto , Homossexualidade Masculina , Felicidade , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Estigma Social , Apoio Social , Fármacos Anti-HIV/uso terapêutico
7.
PLoS One ; 19(1): e0295821, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38170685

RESUMO

INTRODUCTION: A growing body of research has demonstrated extensive mental health disparities affecting sexual minority populations, yet little research has assessed how these disparities may affect cognitive functioning among subgroups of sexual minorities. METHODS: Data come from the 2021 National Health Information Survey (NHIS). Survey-weighted linear regression analyses were used to assess self-reported measures of cognition, stratified by subgroups sexual identity. In particular, we focused on the association between symptoms of depression or anxiety and each of the measures of cognition, adjusting for demographic covariates. RESULTS: Among 31,994 NHIS participants in the 2021 survey, 5,658 (17.7%) reported at least some difficulty in remembering or concentrating. Basic demographic differences existed when assessing any cognitive difficulty, particularly for bisexual participants (aOR = 2.73; 95% CI: 2.07, 3.60) and participants identifying as a different identity (aOR = 4.22; 95% CI: 2.72, 6.56). Depression was significantly associated with cognitive difficulty with the largest relationship observed among gay/lesbian participants (aOR = 1.39; 95% CI: 1.29, 1.49). The association between anxiety and cognitive difficulty was smallest among bisexuals (aOR = 1.13; 95% CI: 1.08, 1.18) and relatively consistent across other subgroups: heterosexuals (aOR = 1.23; 95% CI: 1.22, 1.24), gay/lesbians (aOR = 1.27; 95% CI: 1.19, 1.36), and those with a different identity (aOR = 1.22; 95% CI: 1.10, 1.35). CONCLUSION: There is a clear set of health disparities between sexual minority subgroups and heterosexuals across all cognitive difficulties. Future research should focus on developing a better understanding of differences in cognition based on sexual minority status while also working to ascertain how disparities vary among sexual minorities.


Assuntos
Depressão , Minorias Sexuais e de Gênero , Feminino , Humanos , Depressão/epidemiologia , Depressão/psicologia , Comportamento Sexual/psicologia , Ansiedade , Cognição
8.
bioRxiv ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38293147

RESUMO

Human papillomaviruses (HPV) are a major cause of malignancy, contributing to ∼5% of all human cancers worldwide, including most cervical cancer cases and a growing number of ano-genital and oral cancers. The major HPV viral oncogenes, E6 and E7, manipulate many host cellular pathways that promote cell proliferation and survival, predisposing infected cells to malignant transformation. Despite the availability of highly effective vaccines, there are still no specific anti-viral therapies targeting HPV or treatments for HPV-associated cancers. As such, a better understanding of viral-host interactions may allow the identification of novel therapeutic targets. Here, we demonstrate that the actin-binding protein LASP1 is upregulated in cervical cancer and significantly correlates with a poorer overall survival. In HPV positive cervical cancer, LASP1 depletion significantly inhibited proliferation in vitro , whilst having minimal effects in HPV negative cervical cancer cells. Furthermore, we show that the LASP1 SH3 domain is essential for LASP1-mediated proliferation in these cells. Mechanistically, we show that HPV E7 regulates LASP1 at the post-transcriptional level by repressing the expression of miR-203, which negatively regulated LASP1 mRNA levels by binding to its 3'UTR. Finally, we demonstrated that LASP1 expression is required for the growth of HPV positive cervical cancer cells in an in vivo tumourigenicity model. Together, these data demonstrate that HPV induces LASP1 expression to promote proliferation and survival role in cervical cancer, thus identifying a potential therapeutic target in these cancers.

9.
AIDS Res Hum Retroviruses ; 40(1): 1-6, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37022787

RESUMO

Compared to young heterosexual men, young sexual and gender minorities (YSGM) have elevated systemic inflammation and unique intestinal microbial profiles, influenced by HIV infection and substance use. However, links between cannabis use and microbial dysbiosis in this population have not been well described. In this pilot study, we aimed to characterize the complex interrelationships between cannabis use and microbial community structure in YSGM in relationship to HIV status. Cannabis use was assessed by self-administered Cannabis Use Disorder Identification Test (CUDIT) questionnaires and rectal microbial community alpha-diversity metrics were assessed via 16S ribosomal ribonucleic acid (rRNA) sequencing in a subset of YSGM (n = 42) in the RADAR cohort (aged 16-29) in Chicago. Multivariable regression models were used to assess the relationship between cannabis use and microbiome alpha-diversity metrics, adjusting for HIV status and other risk characteristics, including inflammation, which was evaluated by plasma levels of C-reactive protein (CRP). Problematic cannabis use, but not general use, was significantly inversely associated with microbial community richness (Adj. Beta = -8.13; 95% confidence interval [CI]: -15.68 to -0.59) and Shannon diversity (Adj. Beta = -0.04; 95% CI: -0.07 to 0.009). No significant association was observed between CUDIT score and community evenness, nor was any significant moderation observed by HIV status. We observed that problematic cannabis use was associated with reduced microbial community richness and Shannon diversity, adjusting for within population differences in inflammation and HIV status. Future research should aim to assess how cannabis use contributes to microbiome-related health factors among YSGM and if decreasing cannabis use can restore gut microbial community structure.


Assuntos
Cannabis , Infecções por HIV , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Infecções por HIV/epidemiologia , Cannabis/genética , Projetos Piloto , Inflamação , RNA Ribossômico 16S/genética
10.
J Infect Dis ; 229(1): 232-236, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-37816091

RESUMO

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Sífilis , Adulto , Recém-Nascido , Humanos , Masculino , Estados Unidos/epidemiologia , Sífilis/epidemiologia , Incidência , Estudos Longitudinais , Estudos Prospectivos , Prevalência , Comportamento Sexual , Homossexualidade Masculina , Infecções por HIV/epidemiologia
11.
Subst Use Misuse ; 59(2): 300-305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37853756

RESUMO

Background: Alcohol and illicit substance use remain significant public health issues in the United States. In this analysis, we assessed differences in the use of primary care and emergency departments (EDs) for treatment of substance use among rural and urban sexual minorities (SMs).Methods: Data come from the National Survey on Drug Use and Health (NSDUH, 2015-2019). Survey-weighted multivariable linear and logistic regression analyses were used to assess the relationship between sexual identity and the use of primary care settings or EDs for treatment of substance use, stratified by urbanicity of residence.Results: Among the entire sample, 7.9% reported residing in rural environments with slightly more SMs living in urban (7.3%) relative to rural (5.4%) locales. Both rural (ß=-0.20; 95% CI: -0.29, -0.10) and urban SMs (ß=-0.13; 95% CI: -0.16, -0.11) self-reported worse overall health. Urban SMs, but not rural SMs, had significantly higher odds of reporting use of primary care treatment for substance use (aOR 2.80; 95% CI: 2.13, 3.68). ED treatment for substance use was greater among both rural (aOR = 2.99; 95% CI: 1.01, 8.87) and urban SMs (aOR = 3.02; 95% CI: 2.12, 4.30) as was overall number of ED visits among both rural (ß = 0.48; 95% CI: 0.24, 0.72) and urban SMs (ß = 0.23; 95% CI: 0.19, 0.28) .Conclusion: These findings suggest increased reliance on EDs for treatment of alcohol or substance use among rural SMs. Future research should examine whether increasing culturally competent primary care services for SMs in rural areas may be a key intervention point for reducing health disparities.


Assuntos
Serviço Hospitalar de Emergência , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estados Unidos/epidemiologia , Identidade de Gênero , Inquéritos e Questionários , População Rural , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Atenção Primária à Saúde
12.
J Rural Health ; 40(3): 542-556, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38112341

RESUMO

BACKGROUND: Sexual minority populations are at elevated risk for substance use (SU) and substance use disorders (SUD) compared to heterosexual populations. These disparities are theorized to be amplified for rural sexual minority populations due to their increased exposure to minority stress and reduced access to sexual minority communities. However, there is a lack of research examining differences in SU disparities affecting sexual minority populations by urbanicity, and little research has examined differences in SUD treatment utilization by sexual minority status or urbanicity. METHODS: We utilized data from 2015 to 2019 National Survey on Drug Use and Health to examine disparities in SU, SUD, SUD treatment utilization, and unmet SUD treatment need between sexual minority and heterosexual populations and test whether such disparities vary by urbanicity. RESULTS: Results indicate that disparities in SU and SUD affecting sexual minority populations generalize across urbanicities. A subset of disparities differed by urbanicity, and the direction of these differences varied, with some disparities being stronger in urban than rural populations and vice versa. Despite elevated treatment utilization among some sexual minority groups, disparities in unmet SUD treatment need were prevalent across urbanicities and sexual identity groups. CONCLUSIONS: Study findings highlight the ubiquity of disparities in SU, SUD, and unmet SUD treatment need affecting rural and urban sexual minority populations, while also demonstrating nuanced differences in disparities by urbanicity. The persistence of disparities in unmet SUD treatment need emphasizes the need for future research to identify factors contributing to this disparity and for policies that alleviate these disparities.


Assuntos
População Rural , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , População Urbana , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Masculino , Feminino , Adulto , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Pessoa de Meia-Idade , Adolescente , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estados Unidos/epidemiologia , Inquéritos e Questionários , Grupos Minoritários/estatística & dados numéricos
13.
Alcohol ; 118: 1-7, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37952785

RESUMO

Sexual minorities (SMs; e.g., lesbian, gay, bisexual, and other non-heterosexual individuals) are more likely to be current alcohol drinkers than their heterosexual peers while separately experiencing elevated inflammation. Yet, little research has assessed the association between alcohol use and inflammation among subgroups of SMs, let alone potential differences among people with multiple marginal identities (e.g., race/ethnicity and sexual identity). Data came from the National Health and Nutrition Survey 2015-2016. Survey-weighted multivariable linear regression analysis was used to assess the relationship between alcohol use categories, heavy episodic drinking, and log-CRP (C-reactive protein). Models were stratified by sexual identity to determine whether associations between alcohol use and inflammation or between race/ethnicity and inflammation differed by sexual identity. Among 3220 participants, 1000 (36.8%) reported light alcohol use, 870 (32.0%) reported moderate use, and 483 (17.8%) reported heavy use. Mean raw CRP was 4.1 mg/L (SD = 8.1). The association between race/ethnicity and CRP differed in stratified relative to non-stratified models with key differences in CRP among individuals with multiple marginalized identities. We also observed that while the "classic" J-shaped relationship between alcohol use and systemic inflammation persists among heterosexuals in this sample, it does not hold among subgroups of sexual minorities. In particular, bisexuals who report heavy alcohol use, compared to non-users, experience significantly elevated CRP. Finally, we did not observe any association between heavy episodic drinking and CRP among subgroups of sexual minorities. Future studies assessing alcohol and biomarker data need to strive to include subgroups of sexual minorities and people with multiple marginal identities to better target behavioral and biomedical interventions aimed at reducing health disparities.

14.
Sex Transm Dis ; 50(11): 737-738, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37643401

RESUMO

ABSTRACT: HIV preexposure prophylaxis (PrEP) is a highly effective class of drugs used to prevent the transmission of HIV-1. Despite its high efficacy, the uptake of PrEP has been very low. This project sought to understand the barriers and facilitators to prescribing PrEP in a community health clinic in a Midwestern state.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , Profilaxia Pré-Exposição , Humanos , Fármacos Anti-HIV/uso terapêutico , Atenção Primária à Saúde
15.
Rural Remote Health ; 23(3): 8052, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37643608

RESUMO

INTRODUCTION: Past research has demonstrated that, separately, sexual minorities (SMs) and rural-dwelling populations are each at elevated risk for chronic diseases relative to heterosexuals and urban-dwelling populations, respectively. Little research, however, has assessed whether rural SM populations may experience even further chronic disease risk. METHODS: Data come from the US National Survey on Drug Use and Health, 2015-2019. Survey-weighted logistic regression analyses were used to assess the relationship between sexual identity and various health-associated outcomes, stratified by rural/urban status and adjusted for demographic and other risk factors. RESULTS: Urban bisexual and rural lesbian females had significantly decreased odds of having any health insurance and increased odds of asthma, chronic obstructive pulmonary disease, hepatitis, any heart disease, and STIs relative to their heterosexual counterparts, with disparities affecting bisexual women living in rural areas being largest. Urban gay males had increased odds of having health insurance relative to urban heterosexuals. Both urban gay and bisexual males also experienced increased odds for several chronic diseases, however, among rural residents increased risk was only observed for bisexual males with regards to high blood pressure. CONCLUSION: Rural-dwelling bisexual women experience elevated likelihood for physical health conditions compared to urban-dwelling bisexual women, but few other rural populations experience elevated risk. Urban gay men, meanwhile, are more likely to possess insurance but simultaneously experience worse health outcomes across several domains of diseases, suggesting lower utilization of healthcare services. Future research should strive to avoid pooling all SMs into a single risk group as we have clearly demonstrated that strong differences exist based on both sex and rural/urban status.


Assuntos
Asma , Homossexualidade Feminina , Minorias Sexuais e de Gênero , Masculino , Feminino , Humanos , População Rural , População Urbana
16.
Ann LGBTQ Public Popul Health ; 4(1): 1-13, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37599862

RESUMO

Past research has suggested that sexual and gender minorities experience elevated levels of systemic inflammation which in turn has been linked to worse mental health outcomes. Therefore, the goals of this work are to develop a better understanding of the relationship between mental health variables and inflammation among this high-risk population. Data were collected among a sample of young men who have sex with men and transgender women (YMSM/TGW, N=685) aged 16-20 at the time of enrollment. Multiplex plasma cytokine and inflammatory biomarkers were quantified. Mental health variables were self-reported and included perceived stress, depression, and suicidal ideation. Latent profile analyses (i.e., latent class analyses intended for continuous variables) were utilized to identify four unique profiles of individuals with similar inflammatory markers followed by adjusted multinomial logistic regression to estimate the association between inflammatory profiles and mental health variables. Participants experienced moderate levels of perceived stress, normal levels of depression and ten percent reported suicidal ideation in the past six months. Multinomial regression models indicated that being in the highest inflammation profile, compared to the lowest inflammation profile, was significantly associated only with increased perceived stress and suicidal ideation. In sum, we observed significant relationships between inflammation and both perceived stress and suicidal ideation, but not between inflammation and depression. Future research should continue to assess these relationships using longitudinal data as they are intricate and likely bidirectional and may be key to reducing health disparities among this population.

17.
J Med Virol ; 95(8): e29025, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37565725

RESUMO

Human papillomaviruses (HPVs) infect the oral and anogenital mucosa and can cause cancer. The high-risk (HR)-HPV oncoproteins, E6 and E7, hijack cellular factors to promote cell proliferation, delay differentiation and induce genomic instability, thus predisposing infected cells to malignant transformation. cAMP response element (CRE)-binding protein 1 (CREB1) is a master transcription factor that can function as a proto-oncogene, the abnormal activity of which is associated with multiple cancers. However, little is known about the interplay between HPV and CREB1 activity in cervical cancer or the productive HPV lifecycle. We show that CREB is activated in productively infected primary keratinocytes and that CREB1 expression and phosphorylation is associated with the progression of HPV+ cervical disease. The depletion of CREB1 or inhibition of CREB1 activity results in decreased cell proliferation and reduced expression of markers of epithelial to mesenchymal transition, coupled with reduced migration in HPV+ cervical cancer cell lines. CREB1 expression is negatively regulated by the tumor suppressor microRNA, miR-203a, and CREB1 phosphorylation is controlled through the MAPK/MSK pathway. Crucially, CREB1 directly binds the viral promoter to upregulate transcription of the E6/E7 oncogenes, establishing a positive feedback loop between the HPV oncoproteins and CREB1. Our findings demonstrate the oncogenic function of CREB1 in HPV+ cervical cancer and its relationship with the HPV oncogenes.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Transição Epitelial-Mesenquimal , Proteínas Repressoras/genética , Oncogenes , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética
18.
AIDS Behav ; 27(12): 4033-4040, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37422575

RESUMO

To achieve stated targets in the United States of Ending the HIV Epidemic by 2030, it is necessary to decrease rates of pre-exposure prophylaxis use (PrEP) cessation. In particular, it is key to assess PrEP use and cannabis use frequency given the recent wave of cannabis decriminalization across the U.S., particularly among sexual minority men and gender diverse (SMMGD) individuals. We used data from the baseline visit of a national study of Black and Hispanic/Latino SMMGD. Among participants reporting any lifetime cannabis use, we further assessed the association between frequency of cannabis use in the past 3 months and: (1) self-reported PrEP use, (2) recency of last PrEP dose, and (3) HIV status using adjusted regression models. Compared to those who never used cannabis, odds of PrEP cessation were higher among those who used it once or twice (aOR 3.27; 95% CI 1.38, 7.78), those who used it monthly (aOR 3.41; 95% CI 1.06, 11.01), and those who used it weekly or more frequently (aOR 2.34; 95% CI 1.06, 5.16). Similarly, those reporting cannabis use 1-2 times in the past 3 months (aOR 0.11; 95% CI 0.02, 0.58) and those reporting weekly or more frequent use (aOR 0.14; 95% CI 0.03, 0.68) were each more likely to report more recent PrEP cessation. These results suggest that cannabis users in general may be a population at elevated risk of HIV diagnosis although more research regarding these findings is needed with nationally representative populations.

19.
J Behav Med ; 46(6): 986-995, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37407904

RESUMO

Black and Hispanic/Latino sexual and gender diverse individuals disproportionately experience overlapping health disparities, such as drug use and elevated depressive symptoms, which are often driven by minority stressors. We sought to better understand the interaction between drug use and mental health, as it may be fruitful in developing effective interventions to address co-occurring health disparities. In a longitudinal, 5-wave sample of 300 Black and Hispanic/Latino sexual and gender diverse (SGD) individuals collected between March 2020 and March 2022, we found a within-person association between greater than average levels of psychological distress (depression and anxiety) and more frequent extra-medical use of cannabis, inhalants, methamphetamines, and opioids over the span of two years. These associations held after adjusting for the direct, within-person association of internalized homonegativity with drug use frequency. These results suggest that psychological distress explains at least some variance in drug use among Black and Hispanic/Latino SGD individuals. This highlights the importance of interventions that focus on mental health among Black and Hispanic/Latino SGD individuals who report drug use.


Assuntos
Transtornos Mentais , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Humanos , População Negra/psicologia , População Negra/estatística & dados numéricos , Identidade de Gênero , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Saúde Mental , Comportamento Sexual/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/etnologia , Transtornos Mentais/psicologia , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Desigualdades de Saúde , Angústia Psicológica
20.
J Stud Alcohol Drugs ; 84(6): 874-883, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37449947

RESUMO

OBJECTIVE: Sexual minority individuals are at substantially elevated risk for both cannabis use disorder (CUD) and alcohol use disorder (AUD). Although recent increases in the legalization of cannabis have been linked to increases in cannabis use among the general population, few studies have examined if changes in cannabis use and CUD vary by sexual identity. The purpose of the current study was to examine sexual identity differences in trends for CUD and compare them to trends for AUD. METHOD: We used data from 2015-2019 National Survey on Drug Use and Health to examine annual prevalence and year-specific disparities in cannabis use, CUD, heavy episodic drinking, and AUD. We also examined sex-specific sexual identity differences in linear trends for these substance use outcomes over this 5-year period. RESULTS: All groups except lesbian females experienced significant increases in cannabis use rates from 2015 to 2019. Heterosexual males, heterosexual females, and bisexual females also experienced significant increases in CUD rates. In contrast, no group exhibited significant increases in heavy episodic drinking or AUD rates. Bisexual women exhibited some of the largest year-specific disparities in cannabis use and CUD as well as the largest growth in disparities across time. CONCLUSIONS: The few changes in heavy episodic drinking and AUD alongside numerous changes in cannabis use and CUD suggest that changes in cannabis use may be attributable to legalization of cannabis use in many states during this period. Given profound disparities and increasing rates of CUD affecting bisexual females, further research is needed to identify factors that may explain their disproportionate burden.


Assuntos
Alcoolismo , Cannabis , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Feminino , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Consumo de Bebidas Alcoólicas , Bissexualidade , Alcoolismo/epidemiologia
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