1,720,962 research outputs found

    Hepatitis C Virus and Hepatocellular Carcinoma: Pathogenetic Mechanisms and Impact of Direct-Acting Antivirals

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    INTRODUCTION: Globally, between 64 and 103 million people are chronically infected with Hepatitis C virus (HCV), with more than 4.6 million people in the United States and is associated with more than 15.000 deaths annually. Chronic infection can result in cirrhosis and hepatocellular carcinoma. EXPLANATION: Epidemiological studies have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC), mainly through chronic inflammation, cell deaths, and proliferation. Despite the new direct-acting antiviral drugs (DAA's) being able to clear the HCV, HCC recurrence rate in these patients is still observed. CONCLUSION: In this review we highlighted some aspects that could be involved in the onset of HCV-induced HCC such as immune system, viral factors and host genetics factors.Moreover, we focused on some of the last reports about the effects of DAA's on the HCV clearance and their potential implications in HCC recurrence

    Interferon lambda4 polymorphism is not associated with human papillomavirus infection outcome

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    Interferon (IFN) lambdas are important specific components of the mucosal innate immune response. The IFN lambda 4 (IFNL4) dinucleotide polymorphism (ΔG/TT) determines the IFN lambdas and related Interferon-stimulated genes activation, in HCV and other chronic infections. Our group first reported that IFN Lambda response was impaired in high-risk Human Papillomavirus (HPV) cervical infections and in precancerous lesions. Accordingly, we sought to evaluate the possible role of the IFNL4 polymorphism in determining HPV infection outcome. The ΔG/TT alleles were not differently distributed in 221 women with high- or low-risk HPV infection, with HPV infection clearance or persistence, and with abnormal cytology

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Increased expression of IL-32 correlates with IFN-γ, Th1 and Tc1 in virologically suppressed HIV-1-infected patients

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    Following recent attention focused on IL-32 as an important component involved in the inflammatory cytokine network, we speculated that IL-32's action on IFN-γ and IFN-γ secreting T cell subsets may help sustain the immune activation and dysregulation found in patients with HIV-1 achieving viral suppression. To explore this hypothesis, transcript levels of IL-32 and IFN-γ were evaluated in PBMC from 139 virologically suppressed HIV-1-infected patients and from 63 healthy individuals by Real Time RT-PCR assays. IL-32 and IFN-γ mRNA levels were also analyzed in CD4+ T cells, CD14+ monocytes and lamina propria lymphocytes (LPL) of the gut district in a subgroup of HIV-1-infected subjects. IFN-γ secreting CD4+ (Th1) and CD8+ (Tc1) T cell subset frequencies were evaluated in LPL by multiparametric flow cytometry. Gene expression results revealed that IL-32 and IFN-γ levels in PBMC from HIV-1-positive patients were significantly elevated compared to those from healthy donors, correlated with each other and increased with patient age. Both IL-32 and IFN-γ genes were also more strongly expressed in CD4+ T cells than in CD14+ monocytes. By contrast, IL-32 levels in LPL were comparable to those measured in PBMC, while IFN-γ levels were higher in PBMC than those in LPL. Negative correlations were found between IL-32 levels and the frequencies of Th1 and Tc1 subsets in gut mucosa. Collectively, our results provide the first evidence that IL-32 levels remain elevated in treated HIV-1-infected patients and correlate with IFN-γ, Th1 and Tc1 subsets

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Increased IL-17 and/or IFN-γ producing T-cell subsets in gut mucosa of long-term-treated HIV-1-infected women

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    OBJECTIVE: The influence of sex on gut mucosal T-cell response in HIV-1 infection remains largely unknown. We explored whether the frequencies of interferon-γ and/or IL-17 producing naive, T central memory and T effector memory (TEM) CD4 (Th1, Th17) and CD8 T (Tc1, Tc17) cells measured in gut and peripheral districts differed between female and male HIV-1-infected patients. METHODS: Thirty long-term-treated HIV-1-infected individuals were enrolled. The frequencies of Th1, Th17, Tc1, Tc17-cell subsets (single and double) were evaluated by multiparametric flow cytometry in lamina propria lymphocytes and peripheral blood mononuclear cells (PBMC). RESULTS: A sex-based pattern was recorded in the differences of Th1, Th17, Tc1, Tc17-cell subset (single and double) frequencies between gut and peripheral blood. Female patients had stronger alterations in the gut mucosal T-cell repertoire, especially increased Th1, Th17, and Th1/Th17-cell subset frequencies, compared with the blood district than their male counterparts. Higher naive Tc1, Tc17, Tc1/Tc17, TEM Tc17, and TEM Tc1/Tc17 levels were also recorded in the gut mucosa than in the PBMC of HIV-1-infected women. Males and females also differed in their gut T-cell response, with women being characterized by higher Th1, Th17, Tc1, Tc17, and Th1/Th17 cells subset levels than men. By contrast, only TEM Th1/Th17 and TEM Tc17 in PBMC differed between males and females. CONCLUSION: Sex-based differences observed in the gut T-cell response of HIV-1-infected patients might contribute to the disease dimorphism

    Interferon lambda receptor 1 (IFNL1R) transcript is highly expressed in rhinovirus bronchiolitis and correlates with disease severity

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    BACKGROUND: As the expression of type III IFN receptor is restricted to the mucosal surfaces, its evaluation could be crucial to characterize the role of IFNλs during bronchiolitis. OBJECTIVES: This study was designed to investigate airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus (RSV) or human rhinovirus (HRV) bronchiolitis. STUDY DESIGN: Seventy-one 1-6 month old infants hospitalized with their first episode of acute RSV or HRV bronchiolitis were selected for this study. Expression of IFNLR1, IL10RB and IFN-stimulated genes (ISGs) MxA and ISG56 in cells of nasopharyngeal washings taken within the first 48 h of admission were determined by a real-time hydrolysis probe RT-PCR assay. The ability of types I and III IFNs to induce the expression of both IFNLR1 and IL10RB in vitro was also evaluated. RESULTS: Airway IFNLR1 transcript levels were significantly higher in HRV bronchiolitis infants compared to those with RSV bronchiolitis. No differences were recorded for IL10RB-mRNA between RSV or HRV infection. IFNLR1 mRNA levels increased significantly in infants infected with the C species of HRV and in those with a higher clinical score index and with an eosinophil count >3%. There were no correlations in vivo between type III IFN receptors and those of ISGs and neither IFNLR1 nor IL10RB were induced in vitro by IFNs. CONCLUSIONS: These results suggest that IFNLR1 are increased in HRV-infected infants with more severe bronchiolitis and blood eosinophilia and in those infected with the HRVC species

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    IFN-stimulated gene expression is independent of the IFNL4 genotype in chronic HIV-1 infection

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    This study aimed to evaluate the association between the IFNL4 rs368234815 (ΔG/TT) dinucleotide polymorphism and the IFN response during chronic HIV-1 infection. We carried out genotyping analysis and measured the expression of IFN-stimulated genes (ISGs) (myxovirus resistance protein A [MxA], ISG15, ISG56, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like [APOBEC] 3F and APOBEC3G) on peripheral blood mononuclear cells collected from naïve and HAART-treated HIV-1-infected patients. There were no statistically significant differences in endogenous ISGs mRNA levels among HIV-1-positive patients bearing different IFNL4 genotypes, suggesting that ISG expression is independent of the IFNL4 genotype in HIV-1 infection
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