Racial Microaggressions Mediate the Association Between Posttraumatic Stress and Alcohol Use Among Women of Color Experiencing Intimate Partner Violence.

Objective: Women of Color (WoC) experiencing intimate partner violence (IPV) have elevated rates of posttraumatic stress disorder (PTSD) and alcohol use and related harm (e.g., increased alcohol use and negative consequences). This secondary data analysis assessed the role of racial microaggressions in the association between PTSD and alcohol use and related harm among WoC experiencing IPV. Methods: Participants were 103 WoC currently experiencing IPV and using substances (Mage=40.39, 51.5% Black) who were recruited from the community and completed assessments of PTSD, racial microaggressions, and alcohol use and related harm. Results: Assumptions of Inferiority (e.g., intelligence; B = 1.44, SE = 0.90, 95% CI [0.10, 3.54]) and Environmental Microaggressions (e.g., portrayal in media; B = 1.88, SE = 1.03, 95% CI [0.28, 4.30]) explained the association between PTSD and alcohol use and related harm. Conclusions: Findings underscore the influence of specific microaggressions in the relation between PTSD and alcohol use and related harm among WoC experiencing IPV.

Physiomimetic In Vitro Human Models for Viral Infection in the Liver.

Viral hepatitis is a leading cause of liver morbidity and mortality globally. The mechanisms underlying acute infection and clearance, versus the development of chronic infection, are poorly understood. In vitro models of viral hepatitis circumvent the high costs and ethical considerations of animal models, which also translate poorly to studying the human-specific hepatitis viruses. However, significant challenges are associated with modeling long-term infection in vitro. Differentiated hepatocytes are best able to sustain chronic viral hepatitis infection, but standard two-dimensional models are limited because they fail to mimic the architecture and cellular microenvironment of the liver, and cannot maintain a differentiated hepatocyte phenotype over extended periods. Alternatively, physiomimetic models facilitate important interactions between hepatocytes and their microenvironment by incorporating liver-specific environmental factors such as three-dimensional ECM interactions and co-culture with non-parenchymal cells. These physiologically relevant interactions help maintain a functional hepatocyte phenotype that is critical for sustaining viral hepatitis infection. In this review, we provide an overview of distinct, novel, and innovative in vitro liver models and discuss their functionality and relevance in modeling viral hepatitis. These platforms may provide novel insight into mechanisms that regulate viral clearance versus progression to chronic infections that can drive subsequent liver disease.

Religiosity and hazardous substance use: The moderating role of trauma-related shame.

BACKGROUND AND OBJECTIVES: Hazardous substance use is a major public health concern among individuals with a history of sexual victimization. Although increased religiosity has been known to serve as a protective factor against hazardous substance use, religious individuals with a history of sexual victimization may be at a greater risk for hazardous substance use due to difficulties reconciling sexual victimization with their religious beliefs. Individuals with greater trauma-related shame may engage in hazardous substance use as a means of coping with the traumatic event. METHOD: The present study consisted of 614 participants (Mage = 34.57, 50% women). RESULTS: Results suggested that organizational, nonorganizational, and intrinsic religiosity were positively associated with hazardous alcohol use at higher, but not lower, levels of trauma-related shame. Organizational and intrinsic religiosity were positively associated with hazardous drug use at higher, but not lower, levels of trauma-related shame. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This is the first study to examine the role of trauma-related shame in the relationship between religiosity and hazardous substance use. The findings underline the importance of targeting trauma-related shame in religious individuals with a history of sexual victimization.

Depression and alcohol use in American Indian adolescents: The influence of family factors.

BACKGROUND: Rates of both depression and alcohol use are disproportionately higher among American Indian (AI) adolescents than adolescents in the general population. The co-occurrence of depression and alcohol use is common and clinically relevant given their reciprocal negative influences on outcomes. Family factors may be especially relevant because they could have a buffering effect on this relationship due to the importance of kinship and community in AI communities. The current study examines the roles of family warmth and parental monitoring in the association between depressive symptoms and alcohol use in a large, nationally representative sample of AI adolescents. METHODS: Data were collected from 3498 AI 7th to 12th graders (47.8% female) residing on or near a reservation during the period 2009 to 2013. Participants reported on their depressive symptoms, family factors, and alcohol use. RESULTS: There was a small, but statistically significant positive association between depressive symptoms and alcohol use (r = 0.11, p < 0.001). Greater depressive symptoms were associated with significantly less perceived family warmth (ß = -0.09, 95% CI [-0.13, -0.06]), which was associated with significantly greater alcohol use (ß = -0.39, 95% CI [-0.55, -0.23]). Family warmth significantly accounted for the association between depressive symptoms and alcohol use at high (ß = 0.04, SE = 0.02, 95% CI [0.004, 0.09]), but not low, levels of parental monitoring (ß = 0.02, SE = 0.02, 95% CI [-0.002, 0.06]). CONCLUSIONS: Results of the present study suggest that developing culturally sensitive prevention and treatment approaches focusing on increasing both family warmth and parental monitoring are important to address the co-occurrence of depression and alcohol misuse among AI adolescents.

Modeling reciprocal relations between emotion dysregulation and alcohol use using dynamic structural equation modeling: A micro-longitudinal study.

BACKGROUND: Research examining emotion dysregulation and alcohol use has increased exponentially over the past decade. However, these studies have been limited by their use of cross-sectional designs and narrow definitions of emotion dysregulation. To address these significant gaps in the extant literature, this study utilized state-of-the-art methodology (i.e., experience sampling) and statistics (i.e., dynamic structural equation modeling) to examine potential reciprocal associations between negative and positive emotion dysregulation and alcohol use at the momentary level. METHODS: Participants were 145 community women (mean age = 40.56, 40.3% white) experiencing intimate partner violence (IPV) and using substances. Surveys assessing negative and positive emotion dysregulation and alcohol use (i.e., number of standard drinks) were administered three times a day for 30 days using phone-based interactive voice recording. RESULTS: Significant contemporaneous effects indicated that negative and positive emotion dysregulation both co-occurred with alcohol use. However, levels of negative and positive emotion dysregulation did not predict later alcohol use, nor did alcohol use predict later levels of negative or positive emotion dysregulation. There was significant variability among participants in cross-lagged effects. CONCLUSIONS: Findings showed that negative and positive emotion dysregulation co-occurred with alcohol use and that there was significant interindividual variability in the cross-lagged associations between negative and positive emotion dysregulation and alcohol use. Research using idiographic approaches may identify women experiencing IPV for whom negative and positive emotion dysregulation drive alcohol use and alcohol use drives negative and positive emotion dysregulation.

Examining the Interaction Between Potentially Morally Injurious Events and Religiosity in Relation to Alcohol Misuse Among Military Veterans.

Given the disproportionate rate of alcohol misuse among veterans and related outcomes as compared to the general population, the examination of predictors of alcohol misuse in this population is imperative. Potentially morally injurious events (PMIEs), defined as severe transgressions of a moral code, have been positively associated with alcohol misuse. Exposure to PMIEs may challenge one's religious beliefs, which may, in turn, influence the strength of the association between PMIEs and alcohol misuse among military veterans. The goal of the current study was to examine the potential moderating role of religiosity in the association between PMIEs and alcohol misuse (i.e., alcohol consumption, drinking behaviors, adverse reactions to drinking, and alcohol-related problems). Participants were 496 military veterans in the community (Mage = 37.80 years, SD = 11.42; 70.5% male). The results of moderation analyses indicated that overall religiosity, organizational religiosity, and intrinsic religiosity significantly moderated the association between PMIEs and alcohol misuse such that the positive relation between PMIEs and alcohol misuse was stronger at high versus low levels of religiosity, R2 s = .01. Our findings highlight the importance of considering the role of religiosity in relation to alcohol misuse as a moral injury outcome and the potential utility of tailoring treatments for military veterans who have experienced moral injury.

Posttraumatic Stress Disorder and Substance Misuse Among Black Emerging Adults: The Influence of Social Support.

Objective: Black emerging adults are significantly impacted by substance misuse. Posttraumatic stress disorder (PTSD) is associated with heightened substance misuse among Black emerging adults. However, limited research has identified protective factors that may influence the strength of the relation between PTSD and substance misuse in this population. Addressing this important limitation, the present study examined the potential moderating role of perceived social support in the association between PTSD symptoms and substance (i.e., alcohol and drug) misuse. Methods: Participants were 182 trauma-exposed Black emerging adults (M age = 20.50; 71.3% women) who completed self-report measures assessing PTSD symptoms, alcohol and drug misuse, and perceived social support. Results: PTSD symptoms were significantly and positively correlated with both alcohol and drug misuse. Moderation analyses indicated that positive relations between PTSD symptoms and both alcohol and drug misuse were only significant among Black emerging adults with lower (but not higher) levels of perceived social support. Conclusions: These findings suggest the potential utility of addressing social support in the assessment and treatment of substance misuse in trauma-exposed Black emerging adults.

Racial and ethnic differences in emotion regulation: A systematic review.

OBJECTIVE: Emotion regulation is a transdiagnostic mechanism with relevance to the etiology, maintenance, and treatment of a wide range of clinically relevant outcomes. This study applied systematic review methods to summarize the existing literature examining racial and ethnic differences in emotion regulation. METHODS: We systematically searched four electronic databases (PsycINFO, Embase, MEDLINE, and CINAHL Plus) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the initial 1253 articles, 25 met the inclusion criteria. Findings for emotion regulation strategies generally provide evidence for racial/ethnic differences (71% of reviewed studies), with ethnoracial minorities largely exhibiting greater use of emotion regulation strategies. Whereas the results for emotion regulation potential were slightly more mixed (63% of reviewed studies found racial/ethnic differences), ethnoracial minorities were also largely found to report lower emotion regulation potential. CONCLUSION: This review advances the literature by providing additional support for racial and ethnic differences in emotion regulation.

Exploring the moderating role of gender in the relation between emotional expressivity and posttraumatic stress disorder symptom severity among Black trauma-exposed college students at a historically Black university.

OBJECTIVES: Posttraumatic stress disorder (PTSD) is characterized in part by negative alterations of cognition or mood, including alterations in emotional expressivity, or the extent to which one outwardly displays emotions. Yet, research in this area has relied on predominantly white samples and neglected to consider the potential role of gender, despite there being demonstrated gender differences in both PTSD symptom severity and emotional expressivity, separately. The goal of the current study was to fill a critical gap in the literature by examining the moderating role of gender in the relation between PTSD symptom severity and emotional expressivity in a sample of trauma-exposed Black adults. METHODS: Participants were 207 Black individuals enrolled in a historically Black university in the Southern United States (68.6% female; Mage = 22.32 years). RESULTS: Findings provided support for the moderating role of gender in the association between PTSD symptom severity and emotional expressivity. Specifically, greater PTSD symptom severity was inversely related to emotional expressivity among trauma-exposed Black males and positively associated with emotional expressivity among trauma-exposed Black females. DISCUSSION: These results suggest the potential need for gender-specific assessment and treatment techniques for PTSD symptom severity among trauma-exposed Black college students.

HIV and HCV augments inflammatory responses through increased TREM-1 expression and signaling in Kupffer and Myeloid cells.

Chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) affects an estimated 35 million and 75 million individuals worldwide, respectively. These viruses induce persistent inflammation which often drives the development or progression of organ-specific diseases and even cancer including Hepatocellular Carcinoma (HCC). In this study, we sought to examine inflammatory responses following HIV or HCV stimulation of macrophages or Kupffer cells (KCs), that may contribute to virus mediated inflammation and subsequent liver disease. KCs are liver-resident macrophages and reports have provided evidence that HIV can stimulate and infect them. In order to characterize HIV-intrinsic innate immune responses that may occur in the liver, we performed microarray analyses on KCs following HIV stimulation. Our data demonstrate that KCs upregulate several innate immune signaling pathways involved in inflammation, myeloid cell maturation, stellate cell activation, and Triggering Receptor Expressed on Myeloid cells 1 (TREM1) signaling. TREM1 is a member of the immunoglobulin superfamily of receptors and it is reported to be involved in systemic inflammatory responses due to its ability to amplify activation of host defense signaling pathways. Our data demonstrate that stimulation of KCs with HIV or HCV induces the upregulation of TREM1. Additionally, HIV viral proteins can upregulate expression of TREM1 mRNA through NF-кB signaling. Furthermore, activation of the TREM1 signaling pathway, with a targeted agonist, increased HIV or HCV-mediated inflammatory responses in macrophages due to enhanced activation of the ERK1/2 signaling cascade. Silencing TREM1 dampened inflammatory immune responses elicited by HIV or HCV stimulation. Finally, HIV and HCV infected patients exhibit higher expression and frequency of TREM1 and CD68 positive cells. Taken together, TREM1 induction by HIV contributes to chronic inflammation in the liver and targeting TREM1 signaling may be a therapeutic option to minimize HIV induced chronic inflammation.

Positive emotional intensity and substance use: the underlying role of positive emotional avoidance in a community sample of military veterans.

Background: Military veterans are at greater risk for substance misuse. Positive emotional intensity is one well-established antecedent of substance misuse in this population. Positive emotional avoidance, or attempts to alter the form, frequency, or context of positive emotions, may help to explain this association. While clinical practice typically aims to increase positive emotions, such approaches may have iatrogenic effects, as high-intensity positive emotions may be experienced as distressing and prompt avoidance for some populations. This suggests a need to better understand responses to positive emotions to inform clinical practice.Objectives: The goal of the current study was to advance theory, research, and clinical practice by exploring the role of positive emotional avoidance in the associations between positive emotional intensity and both alcohol and drug misuse. We hypothesized that positive emotional intensity would indirectly influence alcohol and drug misuse through positive emotional avoidance.Methods: Participants were a community sample of United States military veterans recruited through Amazon's Mechanical Turk (n = 535, Mage = 37.45, 71.8% male, 69.5% White).Results: Correlations among positive emotional intensity, positive emotional avoidance, and alcohol and drug misuse were significant and positive (rs range from.13 to.41). Further, positive emotional avoidance was found to account for the relations of positive emotional intensity to alcohol (indirect effect: b =.04, 95%CI [.01,.08]) and drug misuse (indirect effect: b =.01, 95%CI [.01,.02]).Conclusions: Results provide preliminary support for the potential clinical utility of targeting avoidance responses to positive emotions in interventions targeting alcohol and drug misuse among military veterans.

The moderating role of emotion dysregulation in the relation between potentially morally injurious experiences and alcohol misuse among military Veterans.

Alcohol misuse is a serious and pervasive problem among US military Veterans. The commission or omission of acts that transgress important moral standards, known as potentially morally injurious events (PMIEs), has been theoretically and empirically linked to alcohol misuse in this population. Emotion dysregulation has been implicated in the pathogenesis of alcohol misuse and may be relevant in the context of PMIEs. The goal of this study was to examine the roles of negative and positive emotion dysregulation in the relation between PMIEs and alcohol misuse. Participants were a community sample of US military Veterans who were predominantly white (69.5%) and male (71.6%), with a mean age of 38.00. The interaction between PMIEs and both negative and positive emotion dysregulation (separately) significantly predicted alcohol misuse. Simple slopes tests revealed that the relation between PMIEs and alcohol misuse was only significant at high levels of negative and positive emotion dysregulation. Findings underscore the potential utility of targeting both negative and positive emotion dysregulation in alcohol misuse interventions for military Veterans experiencing PMIEs.

17-Beta Hydroxysteroid Dehydrogenase 13 Is a Hepatic Retinol Dehydrogenase Associated With Histological Features of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. A single-nucleotide polymorphism (SNP), rs6834314, was associated with serum liver enzymes in the general population, presumably reflecting liver fat or injury. We studied rs6834314 and its nearest gene, 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13), to identify associations with histological features of NAFLD and to characterize the functional role of HSD17B13 in NAFLD pathogenesis. The minor allele of rs6834314 was significantly associated with increased steatosis but decreased inflammation, ballooning, Mallory-Denk bodies, and liver enzyme levels in 768 adult Caucasians with biopsy-proven NAFLD and with cirrhosis in the general population. We found two plausible causative variants in the HSD17B13 gene. rs72613567, a splice-site SNP in high linkage with rs6834314 (r2 = 0.94) generates splice variants and shows a similar pattern of association with NAFLD histology. Its minor allele generates simultaneous expression of exon 6-skipping and G-nucleotide insertion variants. Another SNP, rs62305723 (encoding a P260S mutation), is significantly associated with decreased ballooning and inflammation. Hepatic expression of HSD17B13 is 5.9-fold higher (P = 0.003) in patients with NAFLD. HSD17B13 is targeted to lipid droplets, requiring the conserved amino acid 22-28 sequence and amino acid 71-106 region. The protein has retinol dehydrogenase (RDH) activity, with enzymatic activity dependent on lipid droplet targeting and cofactor binding site. The exon 6 deletion, G insertion, and naturally occurring P260S mutation all confer loss of enzymatic activity. Conclusion: We demonstrate the association of variants in HSD17B13 with specific features of NAFLD histology and identify the enzyme as a lipid droplet-associated RDH; our data suggest that HSD17B13 plays a role in NAFLD through its enzymatic activity.

Difficulties Regulating Positive Emotions and Substance Misuse: The Influence of Sociodemographic Factors.

Background: Alcohol and drug misuse present significant public health concerns due to their high prevalence and deleterious outcomes. A growing body of research provides support for the role of difficulties regulating positive emotions in alcohol and drug misuse. However, research is needed to better understand for whom difficulties regulating positive emotions are most strongly associated with alcohol and drug misuse to inform assessment and treatment efforts. Objectives: The goal of the present study was to examine potential sociodemographic moderators (i.e. age, gender, ethnicity, race, income, and educational attainment) in the relations between difficulties regulating positive emotions and alcohol and drug misuse. Methods: Participants were 373 trauma-exposed adults (57.1% female, 75.8% White) recruited from the community. Results: Significant differences were identified across sociodemographic groups regarding difficulties regulating positive emotions (i.e. gender, ethnicity, race, and income) and alcohol use (i.e. gender). Moderation analyses revealed a significant interaction between difficulties regulating positive emotions and gender on drug misuse (b = 0.08, p < .001), such that the association was significant for females (b = 0.11, p < .001) but not males (b = .03, p = .05). Conclusions: Results suggest the importance of developing gender-sensitive recommendations for the assessment and treatment of substance misuse, and of incorporating techniques focused on addressing difficulties regulating positive emotions.

Hepatitis B Virus-Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms.

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide. While current therapeutic approaches can efficiently control viral infection, efficient curative antivirals are absent. The understanding of virus-hepatocyte interactions and sensing of viral infection is an important prerequisite for the development of novel antiviral therapies for cure. Hepatocyte intrinsic innate immunity provides a rapid first line of defense to combat viral infection through the upregulation of antiviral and inflammatory genes. However, the functional relevance of many of these antiviral signaling pathways in the liver and their role in HBV pathogenesis is still only partially understood. The recent identification of intracellular RNA and DNA sensing pathways and their involvement in disease biology, including viral pathogenesis and carcinogenesis, is currently transforming our understanding of virus-host interactions. Here the authors review the current knowledge on intrinsic antiviral innate immune responses including the role of viral nucleic acid sensing pathways in the liver. Since HBV has been designated as a "stealth virus," the study of the impact of HBV on signaling pathways in the hepatocyte is of significant interest to understand viral pathogenesis. Characterizing the mechanism underlying these HBV-host interactions and targeting related pathways to enhance antiviral innate responses may open new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with chronic HBV infection.

Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.

A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives. Furthermore, hepatocyte-like cells displayed morphological and functional features characteristic of primary hepatocytes, as indicated by the production of ALB (albumin) and α-1-antitrypsin (A1AT), as well as glycogen storage capacity by periodic acid-Schiff staining. Together, these data support that the small-molecule based hepatic differentiation protocol is a simple, reproducible, and inexpensive method to efficiently drive the differentiation of human pluripotent stem cells towards a hepatocyte-like phenotype, for downstream pharmacogenomic and regenerative medicine applications.

Obstacles to successful treatment of hepatitis C in uninsured patients from a minority population.

BACKGROUND: Hepatitis C virus (HCV) treatment regimens (DAAs) are well tolerated, efficacious but costly. Their high cost and restricted availability, raises concerns about the outcome of treatment in uninsured patients. This study investigated sustained virologic response (SVR) outcomes in a predominately uninsured patient population and completion of four steps along the HCV treatment cascade. METHODS: A retrospective chart review was conducted to characterize the patient population and analyze covariates to determine association with insurance status, attainment of SVR and progression through the HCV treatment cascade. RESULTS: Out of a total of 216 patients, 154 (71%) were uninsured. Approximately 50% of patients (109 of 216 patients) were male and 57% were Hispanic (123 of 216 patients). Sex, race, ethnicity, treatment compliance, and rates of complications were not associated with insurance status. Insured patients were older (median 60 years vs 57 years, p-value < 0.001) and had higher rates of cirrhosis: 32 out of 62 patients (52%) vs 48 out of 154 patients (31%) (p-value = 0.005). Insured patients were tested for SVR at similar rates as uninsured patients: 84% (52 of 62 patients) vs 81% (125 of 154 patients), respectively. Of those tested for SVR, the cure rate for insured patients was 98% (51 out of 52 patients) compared to 97% (121 out of 125 patients) in the uninsured. Out of those who completed treatment, 177 of 189 (94%) were tested for attainment of SVR. Compliance rates were significantly different between tested and untested patients: 88% (156 of 177 patients) vs 0% (0 of 12 patients), respectively (p-value < 0.001). However, insurance status, race ethnicity, cirrhosis, and complications were not associated with being tested for SVR. CONCLUSIONS: These results demonstrate that insured and uninsured patients with chronic HCV infection, with access to patient assistance programs, can be treated and have comparable clinical outcomes. In addition, testing for SVR remains an important obstacle in completion of the HCV treatment cascade. Nevertheless, patient assistance programs remove a significant barrier for treatment access in real-world HCV infected populations.

Hepatitis B Virus and DNA Stimulation Trigger a Rapid Innate Immune Response through NF-κB.

Cell-intrinsic innate immunity provides a rapid first line of defense to thwart invading viral pathogens through the production of antiviral and inflammatory genes. However, the presence of many of these signaling pathways in the liver and their role in hepatitis B virus (HBV) pathogenesis is unknown. Recent identification of intracellular DNA-sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and carcinogenesis suggest a role for these processes in HBV infection. To characterize HBV-intrinsic innate immune responses and the role of DNA- and RNA-sensing pathways in the liver, we used in vivo and in vitro models including analysis of gene expression in liver biopsies from HBV-infected patients. In addition, mRNA and protein expression were measured in HBV-stimulated and DNA-treated hepatoma cell lines and primary human hepatocytes. In this article, we report that HBV and foreign DNA stimulation results in innate immune responses characterized by the production of inflammatory chemokines in hepatocytes. Analysis of liver biopsies from HBV-infected patients supported a correlation among hepatic expression of specific chemokines. In addition, HBV elicits a much broader range of gene expression alterations. The induction of chemokines, including CXCL10, is mediated by melanoma differentiation-associated gene 5 and NF-κB-dependent pathways after HBV stimulation. In conclusion, HBV-stimulated pathways predominantly activate an inflammatory response that would promote the development of hepatitis. Understanding the mechanism underlying these virus-host interactions may provide new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with HBV infection.

Barriers to Hepatitis C Screening in a Minority Population: A Comparison of Hepatitis C and Human Immunodeficiency Virus Screening Rates at a Community STD Clinic in Miami, Florida.

METHODS: 357 patients at a free STD clinic in Miami, FL were screened for HCV. Surveys were administered assessing risk factors for infectious disease transmission, and HCV and HIV screening history. RESULTS: 15.1% of participants had been screened for HCV before whereas 83.8% had been screened for HIV (n = 356). Of the patients previously screened for HCV (n = 54), 98.2% of these patients had previously been screened for HIV as well. CONCLUSION: This data shows the low prevalence of prior HCV screenings in a high-risk population in Miami, FL. Participants who had previously received an HIV screening test were more likely to report receiving a prior HCV screening. Despite the high prevalence of HCV, most HCV infections are undiagnosed. Mortality from HIV has been declining in the United States while mortality from HCV is increasing. To decrease HCV related mortality, we recommend offering HCV screening in conjunction with HIV screening.

Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.

Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase α, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host dependencies yields novel insights into viral infection, pathogenesis and potential therapeutic targets.