RESUMEN
During February 2021-June 2022, the Georgia Department of Public Health (GDPH) detected five clusters of rapid HIV transmission concentrated among Hispanic or Latino (Hispanic) gay, bisexual, and other men who have sex with men (MSM) in metropolitan Atlanta. The clusters were detected through routine analysis of HIV-1 nucleotide sequence data obtained through public health surveillance (1,2). Beginning in spring 2021, GDPH partnered with health districts with jurisdiction in four metropolitan Atlanta counties (Cobb, DeKalb, Fulton, and Gwinnett) and CDC to investigate factors contributing to HIV spread, epidemiologic characteristics, and transmission patterns. Activities included review of surveillance and partner services interview data, medical chart reviews, and qualitative interviews with service providers and Hispanic MSM community members. By June 2022, these clusters included 75 persons, including 56% who identified as Hispanic, 96% who reported male sex at birth, 81% who reported male-to-male sexual contact, and 84% of whom resided in the four metropolitan Atlanta counties. Qualitative interviews identified barriers to accessing HIV prevention and care services, including language barriers, immigration- and deportation-related concerns, and cultural norms regarding sexuality-related stigma. GDPH and the health districts expanded coordination, initiated culturally concordant HIV prevention marketing and educational activities, developed partnerships with organizations serving Hispanic communities to enhance outreach and services, and obtained funding for a bilingual patient navigation program with academic partners to provide staff members to help persons overcome barriers and understand the health care system. HIV molecular cluster detection can identify rapid HIV transmission among sexual networks involving ethnic and sexual minority groups, draw attention to the needs of affected populations, and advance health equity through tailored responses that address those needs.
Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Humanos , Masculino , Georgia/epidemiología , Hispánicos o Latinos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Salud Pública , Disparidades en Atención de SaludRESUMEN
Treatment as prevention (TasP) is an effective HIV prevention strategy. Our objectives were to explore TasP attitudes and beliefs among people with HIV (PWH) who are not engaged in care and to examine attitudes and beliefs by selected characteristics. We sampled PWH who had participated in the Medical Monitoring Project (MMP), a structured interview survey, from June 2018-May 2019 to participate in 60-minute semi-structured telephone interviews. We obtained sociodemographic and behavioral quantitative data from the MMP structured interview. We used applied thematic analysis to analyze the qualitative data and integrated the qualitative and quantitative data during analysis. Negative attitudes and beliefs, especially skepticism and mistrust, about TasP were pervasive. Only one participant who identified as female, was not sexually active, and had not heard of TasP held positive attitudes and beliefs about TasP. TasP messages should use clear and unambiguous language, address mistrust, and reach people who are not engaged in medical care.
Asunto(s)
Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & controlRESUMEN
Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population.
Asunto(s)
Infecciones por VIH , Accesibilidad a los Servicios de Salud , Minorías Sexuales y de Género , Humanos , Masculino , Bisexualidad , Hispánicos o Latinos , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , GeorgiaRESUMEN
Hispanic or Latino (Hispanic) persons with HIV experience disparities in HIV health outcomes compared with some other racial and ethnic groups. A previous report found that the percentages of Hispanic persons who received HIV care, were retained in care, and were virally suppressed were lower than those among non-Hispanic White persons with HIV (1). HIV stigma and discrimination are human rights issues associated with adverse HIV outcomes; eliminating stigma and discrimination among persons with HIV is a national priority*,,§ (2,3). CDC analyzed data from the Medical Monitoring Project (MMP), an annual, cross-sectional study designed to report nationally representative estimates of experiences and outcomes among adults with diagnosed HIV. Data from the 2018-2020 cycles were analyzed to assess self-reported stigma and health care discrimination using adapted versions of validated multi-component scales among 2,690 adult Hispanic persons with HIV in the United States overall and by six characteristics.¶ The median HIV stigma score on a scale of 0-100 was 31.7, with women (35.6) and American Indian or Alaska Native (AI/AN) persons (38.9) reporting the highest scores among Hispanic persons with HIV. HIV stigma was primarily attributed to disclosure concerns (e.g., fearing others will disclose one's HIV status and being careful about who one tells about one's HIV status). Nearly one in four (23%) Hispanic persons with HIV experienced health care discrimination. Health care discrimination was experienced more frequently by Hispanic men (23%) than by Hispanic women (18%) and by Black or African American (Black) Hispanic persons (28%) than by White Hispanic persons (21%). Understanding disparities in experiences of stigma and discrimination is important when designing culturally appropriate interventions to reduce stigma and discrimination.
Asunto(s)
Infecciones por VIH , VIH-1 , Adulto , Negro o Afroamericano , Estudios Transversales , Atención a la Salud , Femenino , Infecciones por VIH/diagnóstico , Hispánicos o Latinos , Humanos , Masculino , Estados Unidos/epidemiologíaRESUMEN
HIV stigma is a barrier to achieving the goals of the US Ending the HIV Epidemic initiative. We analyzed data from the Medical Monitoring Project (MMP) collected during 6/2018-5/2019 from 4050 US adults with diagnosed HIV. We reported national estimates of HIV stigma and assessed their associations with sociodemographic and clinical characteristics. Disclosure concerns and stigma related to negative public attitudes were common. Stigma was higher among younger age groups, women and transgender people, Black and Hispanic/Latino men and women, and Black and Hispanic/Latino men who have sex with men. Stigma was associated with lower antiretroviral therapy use and adherence, missed HIV care visits, and symptoms of depression or anxiety. The estimates presented provide a benchmark from which the nation can monitor its progress. The findings suggest the need for enhanced stigma-reduction efforts among specific groups and the importance of addressing stigma around disclosure and community attitudes.
Asunto(s)
Infecciones por VIH , Personas Transgénero , Adulto , Revelación , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Muestreo , Estigma Social , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Mental health problems ranging from depression to more severe acts such as self-harm or suicidal behaviours are a serious problem among adolescents and young adults. Exposure to violence during the life of young people can increase mental health issues for youth. This study examines the relationship between exposure to violence and mental health issues among youth using a nationally representative study in Malawi. METHODS: We analysed data from the nationally representative Violence Against Children Survey from Malawi (2013) to quantify the association between exposures to violence (physical, sexual and emotional) and their relationship with mental distress, self-harm behaviours and suicidal ideation and attempts among youth aged 13-24 years. We evaluated the association of exposures to violence against children with reported mental health conditions among women and men. We used ordinal logistic regression models with appropriate survey weights to assess exposures to violence and the three outcomes of interest. RESULTS: Children and youth aged 13-24 years exposed to violence in childhood reported higher levels of adverse mental health effects, including mental distress, self-harm behaviours and suicidal ideation and attempts. The odds of reporting these outcomes increased as the number of violence types increased. CONCLUSIONS: Understanding the risks based on different combinations of exposures to violence in Malawi can help identify populations at higher risk and optimise violence prevention strategies.
RESUMEN
Research suggests that language barriers in health care settings may adversely affect clinical outcomes and patient satisfaction. We describe the characteristics of adults with limited English proficiency (LEP) and diagnosed HIV in the United States. The Medical Monitoring Project is a complex sample survey of adults with diagnosed HIV in the United States that uses two-stage, probability-proportional-to-size sampling. We analyzed weighted interview and medical record data collected from June 2015-May 2018. The prevalence of LEP among adults with HIV was 10%. Higher percentages of adults with LEP, compared with adults with English proficiency (EP), were female, Hispanic/Latino, less educated and poor, only had Ryan White HIV/AIDS Program (RWHAP) health care coverage, attended RWHAP-funded facilities, were satisfied with their HIV medical care, were prescribed antiretroviral therapy (ART), were virally suppressed and received testing for sexually transmitted diseases. We found no statistical difference in ART adherence among adults with LEP and EP. Despite the association between LEP and the risk for health disparities, more persons with LEP were virally suppressed compared with persons with EP. One possible explanation is attendance at RWHAP-funded facilities by adults with LEP; however, future studies are needed to explore other possible explanations.
Asunto(s)
Administración Financiera , Infecciones por VIH , Dominio Limitado del Inglés , Barreras de Comunicación , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Cooperación del Paciente , Estados Unidos/epidemiologíaRESUMEN
Homelessness is a challenge to retention in HIV care and adherence to antiretroviral therapy. We describe the sociodemographic and behavioral characteristics of HIV-positive adults who reported recent homelessness. The Medical Monitoring Project is a complex sample survey of HIV-positive adults receiving medical care in the United States. We used weighted interview and medical record data collected from June 2009 to May 2015 to estimate the prevalence of depression, substance use, and HIV risk behaviors among adults experiencing recent homelessness. From 2009 to 2015, 8.3% of HIV-positive adults experienced recent homelessness. Homeless adults were more likely than housed adults to have major depression, to binge drink, use non-injection drugs, use injection drugs, and smoke. Over 60% of homeless adults were sexually active during the past year, with homeless adults reporting more condomless sex with an HIV-negative or unknown status sex partner than housed adults. Programs attempting to improve the health outcomes of HIV-positive homeless persons and reduce ongoing HIV transmission can focus on providing basic needs, such as housing, and ancillary services, such as mental health counseling or substance abuse treatment and counseling.
Asunto(s)
Infecciones por VIH/psicología , Vivienda , Personas con Mala Vivienda/psicología , Salud Mental/estadística & datos numéricos , Asunción de Riesgos , Trastornos Relacionados con Sustancias/complicaciones , Adolescente , Adulto , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Conducta Sexual , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Mucin 1 (MUC1) is a tumor antigen that is aberrantly overexpressed in various cancers, including lung cancer. Our previous in vitro studies showed that MUC1 facilitates carcinogen-induced EGFR activation and transformation in human lung bronchial epithelial cells (HBECs), which along with other reports suggests an oncogenic property for MUC1 in lung cancer. However, direct evidence for the role of MUC1 in lung carcinogenesis is lacking. In this study, we used the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced A/J mouse lung tumor model to investigate the effect of whole-body Muc1 knockout (KO) on carcinogen-induced lung carcinogenesis. Surprisingly, lung tumor multiplicity was significantly increased in Muc1 KO compared to wild-type (WT) mice. The EGFR/AKT pathway was unexpectedly activated, and expression of the EGFR ligand epiregulin (EREG) was increased in the lung tissues of the Muc1 KO compared to the WT mice. EREG stimulated proliferation and protected against cigarette smoke extract (CSE)-induced cytotoxicity in in vitro cultured human bronchial epithelial cells. Additionally, we determined that MUC1 was expressed in human fibroblast cell lines where it suppressed CSE-induced EREG production. Further, suppression of MUC1 cellular activity with GO-201 enhanced EREG production in lung cancer cells, which in turn protected cancer cells from GO-201-induced cell death. Moreover, an inverse association between MUC1 and EREG was detected in human lung cancer, and EREG expression was inversely associated with patient survival. Together, these results support a promiscuous role of MUC1 in lung cancer development that may be related to cell-type specific functions of MUC1 in the tumor microenvironment, and MUC1 deficiency in fibroblasts and malignant cells results in increased EREG production that activates the EGFR pathway for lung carcinogenesis.
Asunto(s)
Transformación Celular Neoplásica/patología , Epirregulina/metabolismo , Receptores ErbB/metabolismo , Neoplasias Pulmonares/patología , Mucina-1/fisiología , Animales , Carcinógenos/toxicidad , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/metabolismo , Células Cultivadas , Epirregulina/genética , Receptores ErbB/genética , Retroalimentación Fisiológica , Femenino , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos A , Ratones Endogámicos C57BL , Ratones Noqueados , Nitrosaminas/toxicidad , Fumar/efectos adversosRESUMEN
The interaction between epithelial and stromal cells through soluble factors such as cytokines plays an important role in carcinogenesis. Breaking this cancer-promoting interaction poses an opportunity for cancer prevention. The tumor-promoting function of interleukin 6 (IL-6) has been documented; however, the underlying mechanisms of this function in lung carcinogenesis are not well elucidated. Here, we show that benzo[a]pyrene diol epoxide (BPDE, the active metabolite of cigarette smoke carcinogen benzo[a]pyrene)-induced human bronchial epithelial cell (HBEC) transformation was enhanced by IL-6 in vitro. The carcinogen/IL-6-transformed cells exhibited higher expression of STAT3 (signal transducer and activator of transcription 3) when compared with cells transformed by BPDE alone. Constitutive STAT3 activation drove cell proliferation and survival through anti-apoptosis gene expression. We further show that quercetin, a dietary compound having preventive properties for lung cancer, decreased BPDE-stimulated IL-6 secretion from human lung fibroblasts through inhibition of the NF-κB and ERK pathways. The inhibition was accomplished at clinically achievable concentrations of the compound. Finally, quercetin blocked IL-6-induced STAT3 activation in HBECs, and IL-6 enhancement of HBEC transformation by BPDE was abolished by quercetin treatment. Altogether, our data reveal novel mechanisms for IL-6 in lung carcinogenesis and for the preventive role of quercetin in the process. © 2015 Wiley Periodicals, Inc.
Asunto(s)
7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/efectos adversos , Transformación Celular Neoplásica/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Interleucina-6/metabolismo , Pulmón/citología , Quercetina/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/patología , Fibroblastos/citología , Fibroblastos/inmunología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Although receptor-interacting protein 1 (RIP1) is well known as a key mediator in cell survival and death signaling, whether RIP1 directly contributes to chemotherapy response in cancer has not been determined. In this report, we found that, in human lung cancer cells, knockdown of RIP1 substantially increased cytotoxicity induced by the frontline anticancer therapeutic drug cisplatin, which has been associated with robust cellular reactive oxygen species (ROS) accumulation and enhanced apoptosis. Scavenging ROS dramatically protected RIP1 knockdown cells against cisplatin-induced cytotoxicity. Furthermore, we found that, in RIP1 knockdown cells, the expression of the hydrogen peroxide-reducing enzyme catalase was dramatically reduced, which was associated with increased miR-146a expression. Inhibition of microRNA-146a restored catalase expression, suppressed ROS induction, and protected against cytotoxicity in cisplatin-treated RIP1 knockdown cells, suggesting that RIP1 maintains catalase expression to restrain ROS levels in therapy response in cancer cells. Additionally, cisplatin significantly triggered the proteasomal degradation of cellular inhibitor of apoptosis protein 1 and 2 (c-IAP1 and c-IAP2), and X-linked inhibitor of apoptosis (XIAP) in a ROS-dependent manner, and in RIP1 knockdown cells, ectopic expression of c-IAP2 attenuated cisplatin-induced cytotoxicity. Thus, our results establish a chemoresistant role for RIP1 that maintains inhibitor of apoptosis protein (IAP) expression by release of microRNA-146a-mediated catalase suppression, where intervention within this pathway may be exploited for chemosensitization.
Asunto(s)
Catalasa/metabolismo , Proteínas Inhibidoras de la Apoptosis/biosíntesis , MicroARNs/biosíntesis , Neoplasias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/biosíntesis , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Catalasa/genética , Línea Celular Tumoral , Cisplatino/farmacología , Técnicas de Silenciamiento del Gen , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , MicroARNs/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Inhibidora de la Apoptosis Ligada a X/genéticaRESUMEN
Given the increased marijuana use, negative health consequences of marijuana secondhand smoke exposure (SHSe) and dearth of research regarding marijuana SHSe in personal settings, we examined the prevalence and correlates of allowing marijuana versus cigarette smoking in personal settings among 2002 online survey respondents at two southeastern US universities in 2013. Findings indicated that 14.5% allowed cigarettes in the home, 17.0% marijuana in the home, 35.9% cigarettes in cars and 27.3% marijuana in cars. Allowing cigarettes in the home was associated with younger age, racial/ethnic minority status, living off campus, personal marijuana use, parental tobacco use and positive perceptions of cigarettes (P < 0.05). Correlates of allowing marijuana in the home included older age, not having children, living off campus, positive perceptions of marijuana and personal, parental and friend marijuana use (P < 0.05). Correlates of allowing cigarettes in cars included personal cigarette and marijuana use, parental tobacco and marijuana use, more cigarette-smoking friends and positive perceptions of cigarettes (P < 0.05). Correlates of allowing marijuana in cars included being non-Hispanic black; positive perceptions of marijuana; and personal, parental and friend marijuana use (P < 0.05). Interventions must target distinct factors influencing policies regarding cigarette versus marijuana use in personal settings to address the consequences of marijuana and cigarette SHSe.
Asunto(s)
Automóviles , Vivienda , Fumar Marihuana/epidemiología , Fumar/epidemiología , Estudiantes/estadística & datos numéricos , Negro o Afroamericano , Factores de Edad , Estudios Transversales , Femenino , Humanos , Masculino , Fumar Marihuana/etnología , Percepción , Prevalencia , Fumar/etnología , Factores Socioeconómicos , Sudeste de Estados Unidos , Universidades , Adulto JovenRESUMEN
Acquired chemoresistance is a major challenge in cancer therapy. While the oncoprotein Mucin-1 (MUC1) performs multiple roles in the development of diverse human tumors, whether MUC1 is involved in acquired chemoresistance has not been determined. Using an acquired chemoresistance lung cancer cell model, we show that MUC1 expression was substantially increased in cells with acquired apoptosis resistance (AR). Knockdown of MUC1 expression effectively increased the sensitivity of these cells to the apoptotic cytotoxicity of anticancer therapeutics, suggesting that MUC1 contributes to acquired chemoresistance. Decreased catalase expression and increased cellular reactive oxygen species (ROS) accumulation were found to be associated with MUC1 overexpression. Scavenging ROS with butylated hydroxyanisole or supplying exogenous catalase dramatically suppressed MUC1 expression through destabilizing MUC1 protein, suggesting that reduced catalase expression mediated ROS accumulation is accounted for MUC1 overexpression. Further, we found that increased miR-551b expression in the AR cells inhibited the expression of catalase and potentiated ROS accumulation and MUC1 expression. Finally, by manipulating MUC1 expression, we found that MUC1 promotes EGFR-mediated activation of the cell survival cascade involving Akt/c-FLIP/COX-2 in order to protect cancer cells from responding to anticancer agents. Thus, our results establish a pathway consisting of miR-551b/catalase/ROS that results in MUC1 overexpression, and intervention against this pathway could be exploited to overcome acquired chemoresistance.
Asunto(s)
Apoptosis/genética , Catalasa/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Mucina-1/biosíntesis , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Mucina-1/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Hispanic/Latino people with HIV (PWH) experience disparities in health outcomes compared with other racial and ethnic groups. Disaggregated data based on race for Hispanic/Latino PWH in the United States are rarely reported, potentially masking inequities. METHODS: The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV. We used weighted interview and medical record data collected from June 2015-May 2021 to examine differences in social determinants of health (SDH) and health outcomes by self-reported race among Hispanic/Latino adults with diagnosed HIV. RESULTS: Compared with White Hispanic/Latino PWH, Black Hispanic/Latino PWH were more likely to be unemployed (PR, 1.4; CI, 1.2-1.8), have a disability (PR, 1.3; CI, 1.2-1.5), have experienced homelessness (PR, 1.8; CI, 1.2-2.6), and have been incarcerated (PR, 2.6; CI, 1.5-4.5). American Indian/Alaska Native (AI/AN) (PR, 1.8; CI, 1.1-2.7) and multiracial (PR, 2.0; CI, 1.4-2.9) Hispanic/Latino PWH were more likely to have experienced homelessness than White Hispanic/Latino PWH. Black (PR, 1.3; CI, 1.2-1.5) and multiracial (PR, 1.2; CI, 1.1-1.5) Hispanic/Latino PWH were more likely to be virally unsuppressed than White Hispanic/Latino PWH. CONCLUSION: Black, multiracial, and AI/AN Hispanic/Latino PWH experience disparities in SDH and HIV outcomes. Lumping Hispanic/Latino people into one racial and ethnic category obscures health disparities, which might limit our progress towards reaching national HIV goals. Future studies should consider disaggregating by other factors such as Hispanic origin, place of birth, immigration status, and primary language. Doing so recognizes the diversity of the Hispanic/Latino population.
Asunto(s)
Infecciones por VIH , Hispánicos o Latinos , Determinantes Sociales de la Salud , Adulto , Humanos , Factores Raciales , Estados Unidos/epidemiologíaRESUMEN
Cell survival signaling is important for the malignant phenotypes of cancer cells. Although the role of receptor-interacting protein 1 (RIP1) in cell survival signaling is well documented, whether RIP1 is directly involved in cancer development has never been studied. In this report, we found that RIP1 expression is substantially increased in human non-small cell lung cancer and mouse lung tumor tissues. RIP1 expression was remarkably increased in cigarette smoke-exposed mouse lung. In human bronchial epithelial cells (HBECs), RIP1 was significantly induced by cigarette smoke extract or benzo[a]pyrene diol epoxide (BPDE), the active form of the tobacco-specific carcinogen benzo(a)pyrene. In RIP1 knockdown HBECs, BPDE-induced cytotoxicity was significantly increased, which was associated with induction of cellular reactive oxygen species (ROS) and activation of mitogen-activated protein kinases (MAPKs), including c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38. Scavenging ROS suppressed BPDE-induced MAPK activation and inhibiting ROS or MAPKs substantially blocked BPDE-induced cytotoxicity, suggesting ROS-mediated MAPK activation is involved in BPDE-induced cell death. The ROS-reducing enzyme catalase is destabilized in an ERK- and JNK-dependent manner in RIP1 knockdown HBECs and application of catalase effectively blocked BPDE-induced ROS accumulation and cytotoxicity. Importantly, BPDE-induced transformation of HBECs was significantly reduced when RIP1 expression was suppressed. Altogether, these results strongly suggest an oncogenic role for RIP1, which promotes malignant transformation through protecting DNA-damaged cells against carcinogen-induced cytotoxicity associated with excessive ROS production.
Asunto(s)
Células Epiteliales/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Estrés Oxidativo , Proteínas de Unión al ARN/genética , Especies Reactivas de Oxígeno/metabolismo , Animales , Bronquios/metabolismo , Bronquios/patología , Catalasa/metabolismo , Supervivencia Celular , Daño del ADN/genética , Células Epiteliales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Ratones , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Unión al ARN/metabolismo , FumarRESUMEN
Despite decades of research in defining the health effects of low-dose (<100 mGy) ionizing photon radiation (LDR), the relationship between LDR and human cancer risk remains elusive. Because chemical carcinogens modify the tumor microenvironment, which is critical for cancer development, we investigated the role and mechanism of LDR in modulating the response of stromal cells to chemical carcinogen-induced lung cancer development. Secretion of proinflammatory cytokines such as interleukin-6 (IL-6), CXCL1 and CXCL5 from human lung fibroblasts was induced by cigarette-smoke carcinogen benzo[a]pyrene diol epoxide (BPDE), which was inhibited by a single dose of LDR. The activation of NF-κB, which is important for BPDE-induced IL-6 secretion, was also effectively suppressed by LDR. In addition, conditioned media from BPDE-treated fibroblasts activated STAT3 in the immortalized normal human bronchial epithelial cell line Beas-2B, which was blocked with an IL-6 neutralizing antibody. Conditioned medium from LDR-primed and BPDE-treated fibroblast showed diminished capacity in activating STAT3. Furthermore, IL-6 enhanced BPDE-induced Beas-2B cell transformation in vitro. These results suggest that LDR inhibits cigarette smoke-induced lung carcinogenesis by suppressing secretion of cytokines such as IL-6 from fibroblasts in lung tumor-prone microenvironment.
Asunto(s)
Bronquios/efectos de los fármacos , Carcinógenos/toxicidad , Interleucina-6/efectos de la radiación , Pulmón/efectos de la radiación , Humo , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/toxicidad , Bronquios/citología , Transformación Celular Neoplásica , Relación Dosis-Respuesta en la Radiación , Células Epiteliales/efectos de los fármacos , Fibroblastos/efectos de la radiación , Rayos gamma , Humanos , Interleucina-6/metabolismo , Pulmón/metabolismo , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , NicotianaRESUMEN
Treating people with HIV (PWH) quickly and effectively to achieve viral suppression is a key strategy for Ending the HIV Epidemic. Understanding barriers and facilitators to HIV care engagement could improve outcomes among PWH and reduce HIV infections. We sampled PWH who participated in the Medical Monitoring Project from June 2018 to May 2019 and were not engaged in HIV care to participate in 60-min semistructured telephone interviews on barriers and facilitators to HIV care engagement. We used applied thematic analysis and placed codes into themes based on their frequency and salience. Participants reported various intrapersonal, health system, and structural barriers to care. We conceptualize the boundary of care as the space between the stages of the HIV care continuum, where PWH may find themselves when they lack intrapersonal, health system, and structural support. Research and interventions tackling these barriers are needed to improve outcomes among PWH and reduce HIV infections.
Asunto(s)
Infecciones por VIH , Continuidad de la Atención al Paciente , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Accesibilidad a los Servicios de Salud , Humanos , Aceptación de la Atención de Salud , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The Medical Monitoring Qualitative (MMP-Qual) Project was designed to collect qualitative data from people with HIV not engaged in medical care that would complement quantitative data collected by the Medical Monitoring Project (MMP)-a national surveillance system-and inform the MMP's recruitment and data collection methods. OBJECTIVE: Our objectives were to describe the methodology of this project, reflect on the challenges and lessons learned from conducting qualitative telephone interviews at a national level, and describe how we used and plan to use the qualitative data to evaluate our recruitment procedures and quantitative data collection instrument as well as knowledge of HIV care engagement. METHODS: We used stratified purposive sampling to identify and recruit participants who had participated in the structured MMP interview into the MMP-Qual Project. To be eligible, participants must have had an HIV diagnosis, be aged ≥18 years, have lived in an MMP jurisdiction, and have not been engaged in HIV medical care. From August 1, 2018, to May 31, 2019, we conducted semistructured telephone interviews with 36 people with HIV across the United States about several topics (eg, facilitators and barriers to care and experience with surveys). Four trained interviewers conducted semistructured 60-minute telephone interviews with 36 participants. Data collection lasted from August 1, 2018, to May 31, 2019. RESULTS: From 2018 to 2019, 113 people were eligible to participate in the MMP-Qual Project. Of the people recruited, 28% (22/79) refused to participate. Of those who agreed to participate, 63% (36/57) were interviewed, and 37% (21/57) were no-shows. Of the 34 participants for whom we had complete data, 15 (44%) were aged ≥50 years, 26 (76%) identified as male, 22 (65%) were Black or African American, and 12 (35%) lived in the Southern United States. CONCLUSIONS: We learned that it is possible to obtain rich qualitative data from people with HIV who are not in care via telephone interviews and that this mode might be conducive to talking about sensitive topics. We also learned the importance of flexibility, communication, and coordination because we relied on health department staff to perform recruitment and had difficulty implementing our original sampling strategy. We hope that other projects will learn from our experience conducting qualitative telephone interviews with people with HIV on a national level. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/40041.
RESUMEN
ABSTRACT: People living with HIV (PLWH) who experience homelessness have poorer clinical outcomes than people with HIV who are not homeless; however, there is limited information on PLWH who experience other forms of housing instability. We used interviews and medical record abstraction data from the Medical Monitoring Project, collected 2018-2019 (N = 4,050), to describe sociodemographic characteristics and clinical outcomes of adults with HIV by whether people experienced unstable housing in the past 12 months. Overall, 21% were unstably housed, of which 55.2% were unstably housed but not homeless. People who were unstably housed were more likely to be younger, have lower educational attainment, be previously incarcerated, live at or below the poverty level, and have poorer mental health and clinical outcomes, independent of homelessness. Interventions to address housing instability, integrated with clinical care, could benefit not just PLWH who are homeless but also those who are unstably housed.
Asunto(s)
Infecciones por VIH , Personas con Mala Vivienda , Adulto , Centers for Disease Control and Prevention, U.S. , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Vivienda , Inestabilidad de Vivienda , Humanos , Estados Unidos/epidemiologíaRESUMEN
We (1) estimated the prevalence of not getting patient navigation despite feeling a need for the service (unmet subjective need) or despite having unsuppressed viral load (unmet objective need) among people with HIV (PWH), (2) determined reasons why PWH did not use the service, and (3) determined factors associated with unmet need for patient navigation. We used combined data from the 2015 to 2017 cycles of the Medical Monitoring Project, an HIV surveillance system designed to produce nationally representative estimates of the characteristics of adults with diagnosed HIV infection in the United States. Six percent reported unmet subjective need and 28% had unmet objective need for patient navigation. When needs were combined, more than a third had unmet need for the service. Among PWH with unmet subjective need for patient navigation, 77% reported lack of knowledge about patient navigation as a reason for nonuse. Younger age, female gender, racial/ethnic minority status, limited health literacy, homelessness, incarceration history, lack of health insurance/coverage, noninjection drug use, depression, and recent HIV diagnosis were associated with unmet subjective or objective need for patient navigation. One in three PWH did not use patient navigation despite needing the service. Lack of knowledge about patient navigation was a barrier to use, calling for increased availability, and promotion of such services. PWH with social and economic vulnerabilities were less likely to get patient navigation when needed. It is important to address the question of how to make this service available to everyone who needs it.