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Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.

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Objectives: The objectives of our study were to determine the prevalence of major depressive symptoms and identify factors that are associated with major depressive symptoms among Black men with prostate cancer (PCa). Design: This study consisted of 415 Black men aged 40-81 years that entered the North Carolina Central Cancer Registry during the years 2007-2008. The primary outcome variable was depressive symptoms (CES-D). Factors included age, income, education, insurance status, treatment received, time between diagnosis and treatment, Gleason score, medical mistrust and experience with racism/discrimination. Logistic regression models were used to assess factors associated with the odds of having major depressive symptoms. Results: The prevalence of major depressive symptoms (≥16 on CES-D) among our sample of Black men with PCa was approximately 33%. Approximately 15% of the study participants underwent radiation beam treatment. Age was significantly associated with the odds of reporting major depressive symptoms (OR= .95, CI .91-.99) among Black men. In addition, compared with all other forms of treatment, Black men who underwent radiation beam treatment had higher odds (OR=2.38, CI 1.02- 5.51) of reporting major depressive symptoms. Conclusion: Nearly one-third of Black men with PCa in this study reported major depressive symptoms. Clinicians should pay closer attention to the mental health status of Black men with PCa, especially those who are younger and those who have undergone radiation beam treatment. Cancer survivorship, particularly quality of life, may be enhanced by opportunities for assessment, evaluation and intervention of depressive symptoms among these men disproportionately affected by PCa.

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BACKGROUND: Medical mistrust is thought to affect health care-based decisions and has been linked to poor health outcomes. The effects of medical mistrust among men with prostate cancer are unknown. Thus, the goal of the current study is to examine the association between medical mistrust and quality of life (QOL) among black and white men with prostate cancer. METHODS: A total of 877 men (415 black, 462 white) with prostate cancer between the ages of 40 to 81 years who entered the North Carolina Central Cancer Registry during the years 2007 and 2008 were retrospectively recruited. The dependent variable was overall QOL measured by the Functional Assessment of Cancer Therapy-Prostate questionnaire. The primary independent variable was medical mistrust. Multivariate regression analysis was used to assess the association between medical mistrust and overall QOL. RESULTS: Compared with white men, black men reported a higher level of medical mistrust (black = 2.7, white = 2.4; P < .001) and lower QOL (black = 134.4, white = 139.5; P < 0.001). After controlling for demographical and clinical variables, higher levels of medical mistrust were associated with a reduction in overall QOL among men with prostate cancer (beta = -7.73; standard error = 1.54) CONCLUSIONS: Higher levels of medical mistrust are associated with reduced overall QOL among black and white men with prostate cancer. Interventions targeted to reduce medical mistrust may be effective in increasing the overall QOL of men with prostate cancer.

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BACKGROUND: Findings from previous research has demonstrated a positive relationship between interpersonal discrimination and cigarette smoking. Cigarette smoking is proposed to be an externalizing coping mechanism used to alleviate discrimination. At the national level, it is unclear if discrimination is associated with cigarette smoking among African American men. OBJECTIVE: The aim of the study was to examine the association between discrimination and cigarette smoking among a national sample of African American men. METHODS: Using data from the National Survey of American Life (n = 1,271), multivariable logistic regression was used to examine the relationship between discrimination and cigarette smoking. RESULTS: Thirty-two percent of the men were current smokers. Controlling for everyday discrimination, major discrimination, major stress, depressive symptoms, age, being married, household income, and education, African American men who experienced major discrimination had a higher odd of being a current smoking (odds ratio: 1.11, 95% confidence interval: 1.02-1.21) than African American men who did not experience major discrimination. Conclusion/Importance: Findings suggest that African American men may use cigarette smoking as a mechanism to alleviate the experiences of discrimination. Future studies should continue to examine factors associated with African American men's smoking behavior in efforts to inform culturally relevant interventions.

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BACKGROUND: Disparities among patients with prostate cancer exist across the continuum of care. The interval of time that lapses between first diagnosis and treatment is another disparity that may exist but has not been fully explored. METHODS: Our study looked at the data of 749 men (353 black and 396 white) who were 40 to 81 years of age when they entered the North Carolina Central Cancer Registry during the years 2007 and 2008. Our dependent variable was the amount of months that had passed between first diagnosis and treatment. Our main independent variable was self-reported race. Covariates included age, income, level of education, insurance status, treatment received, Gleason score, and level of medical mistrust. We used negative binomial regression analysis to determine the association between the amount of time that lapsed between a diagnosis of prostate cancer and treatment by race. RESULTS: Compared with white men, black men were more likely to experience a longer wait time between diagnosis and treatment of prostate cancer (incidence rate ratio [IRR] 1.19; 95% confidence interval [CI], 1.04-1.36). Controls for demographical, clinical, and psychosocial variables (IRR 1.24; 95% CI, 1.04-1.43) did not explain this difference between the races. CONCLUSIONS: These results suggest that the amount of time that lapses between first diagnosis and treatment of prostate cancer is longer for black men compared with white men. Our findings have identified an underreported racial disparity in the disease continuum of prostate cancer.

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The objective of this study is to examine factors among a group of African American and White men in North Carolina and their assessment of prostate cancer treatment choice or belief that treatment chosen was best. A sample of men (N = 877) with a history of prostate cancer diagnosis was recruited from the North Carolina Cancer Registry during 2007-2008 and asked to participate in a telephone interview covering several measures about their initial prostate cancer treatment. Logistic regression was used to assess demographic, psychosocial, and clinical factors on whether they felt that they had chosen the best treatment for the disease. Respondents were majority White (52.7 %), married (75.9 %), and had surgery (67.9 %) as their initial treatment. At the bivariate level, factors associated with the belief that the treatment chosen was best were as follows: White race/ethnicity, higher levels of education, a more recent treatment date, having health insurance coverage, type of treatment received, higher levels of bother from side effects, greater contentment with their quality of life, and doctor discussions of the various treatment options. Similarly, the multivariate analysis showed increased odds of belief that the treatment chosen was the best among demographic (i.e., race/ethnicity, level of education, and health insurance coverage) as well as psychosocial and clinical variables (i.e., greater bother from side effects, greater contentment with their quality of life, and initial treatment received). Results suggest that demographic, psychosocial, and clinical factors play an important role for men in assessing their treatment choices for prostate cancer.

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GB virus type C (GBV-C) glycoprotein E2 protein disrupts HIV-1 assembly and release by inhibiting Gag plasma membrane targeting, however the mechanism by which the GBV-C E2 inhibits Gag trafficking remains unclear. In the present study, we identified ADP-ribosylation factor 1 (ARF1) contributed to the inhibitory effect of GBV-C E2 on HIV-1 Gag membrane targeting. Expression of GBV-C E2 decreased ARF1 expression in a proteasomal degradation-dependent manner. The restoration of ARF1 expression rescued the HIV-1 Gag processing and membrane targeting defect imposed by GBV-C E2. In addition, GBV-C E2 expression also altered Golgi morphology and suppressed protein traffic through the secretory pathway, which are all consistent with a phenotype of disrupting the function of ARF1 protein. Thus, our results indicate that GBV-C E2 inhibits HIV-1 assembly and release by decreasing ARF1, and may provide insights regarding GBV-C E2's potential for a new therapeutic approach for treating HIV-1.

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A growing body of research seeks to conceptualize race as a multi-dimensional construct, attempting to move beyond a dummy variable approach to study social disparities. This research uses 'socially-assigned race', 'ascribed race', or 'what race others think you are' as opposed to self-identified race to assess self-rated health status among a representative study of the Latino population (n = 1,200). Our analysis shows how important the lived experience of Latinos and Hispanics (as measured by ascribed race and a host of control variables, including nativity and national origin) is on self-reported health. Using a series of logistic regressions, we find support for the 'white advantage' in Latino health status that is suggested in the literature, but this finding is sensitive to nativity, citizenship, and national origin. This research informs the study of racial and ethnic disparities, providing a detailed explanation for the 'white health advantage' finding within the socially-assigned race and health disparities literature.

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BACKGROUND: HIV-1 viral infectivity factor (Vif) is an essential accessory protein for HIV-1 replication. The predominant function of Vif is to counteract Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G, A3G), a potent host restriction factor that inhibits HIV-1 replication. Vif mediates the proteasomal degradation of A3G and inhibits A3G translation, thus diminishing the pool of A3G that is available to be packaged into budding virion. Although Vif is robust in degrading A3G, the protection provided against A3G is not absolute. Clinical and laboratory evidence have shown that A3G is not completely excluded from HIV-1 viral particles during HIV-1 replication. It remains unclear why the viral samples are still infectious when A3G has been packaged into the virions. RESULTS: In this study, we provide evidence that Vif continues to protect HIV-1 from the deleterious effects of A3G, even after packaging of A3G has occurred. When equal amounts of A3G were packaged into budding virions, the virus expressing functional Vif was more infectious and incurred fewer G to A hypermutations in the second round of infection compared to Vif-deficient virus. A Vif mutant with a defect in viral packaging showed a reduced ability to protect the HIV-1 genome from G to A hypermutations. CONCLUSION: Our data suggest that even packaged A3G is still under the tyranny of Vif. Our work brings to light an additional caveat for any therapy that hopes to exploit the Vif-A3G axis. The ideal strategy would not only enhance A3G viral packaging, but also reduce HIV-1 Vif viral encapsidation.

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Although most human immunodeficiency virus type 1 (HIV-1) cases worldwide are transmitted through mucosal surfaces, transmission through the oral mucosal surface is a rare event. More than 700 bacterial species have been detected in the oral cavity. Despite great efforts to discover oral inhibitors of HIV, little information is available concerning the anti-HIV activity of oral bacterial components. Here we show that a molecule from an oral commensal bacterium, Streptococcus cristatus CC5A can induce expression of APOBEC3G (A3G) and APOBEC3F (A3F) and inhibit HIV-1 replication in THP-1 cells. We show by qRT-PCR that expression levels of A3G and A3F increase in a dose-dependent manner in the presence of a CC5A extract, as does A3G protein levels by Western blot assay. In addition, when the human monocytic cell line THP-1 was treated with CC5A extract, the replication of HIV-1 IIIB was significantly suppressed compared with IIIB replication in untreated THP-1 cells. Knock down of A3G expression in THP-1 cells compromised the ability of CC5A to inhibit HIV-1 IIIB infectivity. Furthermore, SupT1 cells infected with virus produced from CC5A extract-treated THP-1 cells replicated virus with a higher G to A hypermutation rate (a known consequence of A3G activity) than virus used from untreated THP-1 cells. This suggests that S. cristatus CC5A contains a molecule that induces A3G/F expression and thereby inhibits HIV replication. These findings might lead to the discovery of a novel anti-HIV/AIDS therapeutic.

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BACKGROUND: While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells. CONCLUSIONS/SIGNIFICANCE: Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.

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