The chemokine CXCL-8 (interleukin-8) is induced by many viruses, including hepatitis C virus (HCV).In the current study, we examined CXCL-8 levels in the context of acute and chronic HCV replication in vitro. Two different small interfering RNAs were used to silence CXCL-8 mRNA and protein expression in Huh7 and BB7 replicon cells. HCV RNA synthesis in BB7 cells was inhibited by CXCL-8 knockdown. Furthermore, antibody neutralization of endogenous CXCL-8 activity inhibited HCV replication, while addition of recombinant human CXCL-8 stimulated NS5A protein expression. Moreover, CXCL-8 protein levels correlated positively with HCV RNA levels in four independent subgenomic and genomic replicon lines (R ‫؍‬ 0.41, P ‫؍‬ 0.0013). However, CXCL-8 mRNA levels correlated inversely with CXCL-8 protein and HCV RNA levels in all replicon lines and in Huh7 cells. Transient replication assays with strongly permissive and weakly permissive Huh7 cells and three independent subgenomic replicons with various replicative capacities revealed that CXCL-8 protein levels were higher in weakly than in strongly permissive cells. The JFH-1 subgenomic replicon, which replicated to high levels in both strongly and weakly permissive Huh7 cells, induced CXCL-8 protein to high levels in both cell types. The data indicate that in the replicon system, CXCL-8 protein levels are positively associated with chronic HCV replication and that CXCL-8 removal inhibits HCV replication. During acute HCV replication, CXCL-8 production may be inhibitory to viruses with low replicative capacity. The data underscore the complex regulation of CXCL-8 mRNA and protein expression and further suggest that in addition to contributing to HCV pathology via proinflammatory actions, CXCL-8 may have opposing antiviral and proviral effects depending on the level of HCV replication, the cellular context, and whether the infection is acute or chronic.Infection with hepatitis C virus (HCV) is a serious medical issue. HCV is unique among hepatitis viruses in that the majority (Ͼ70%) of acutely infected individuals progress to chronic infection, resulting in an estimated 170 million infected individuals worldwide. Chronic HCV infection is thus a major cause of liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma (2).Cloned in 1989 (7), HCV encodes a single polyprotein precursor that is cleaved when expressed in cell culture into at least 10 proteins. The first third of the genome encodes the structural proteins that form the virion. They include the core protein, two envelope proteins (E1 and E2), and a small protein with ion channel functions (P7). An additional open reading frame in the core gene has recently been described, although the role of this protein in HCV replication and pathogenesis remains to be determined. Nonstructural proteins are derived from the remaining two-thirds of the polyprotein and include NS2, NS3 (a serine protease/helicase), NS4A, NS4B, NS5A, and NS5B (the RNA-dependent RNA polymerase). Despite extensive genetic and biochemica...

No abstract

Glasgow, Montana has a significant rate of pregnancy and alcohol abuse among teens. Further, the male-dominated “good ol' boy” mentality that is prevalent in the community hinders the development of confident, independent young women. It has been shown that low self-esteem leads to poor health behaviors, such as pregnancy, problem eating, and alcohol abuse, among teens. These factors, along with discussions with health professionals, combined to indicate the importance of developing a project directed at building self-esteem within the young women and girls of the community. The project was designed in two parts in order to be most effective and reach the greatest population. First, a brochure was developed that identified the importance of self-esteem and what to do to help build self-esteem. The brochure was then distributed to the mental health center in Glasgow for use within the clinic and in the school system. Second, a talk was given at a girl's group meeting focusing on similar topics as the brochure. Activities were also undertaken to help the girls better understand the range of topics presented. After talking at the girl's group, an informal survey was taken which showed that the girls grasped basic concepts, such as respecting themselves and others for who they are, but had difficulty understanding the concepts of self-esteem and why it is important. A program developed within the school system that has the capacity to reach the most girls would be very beneficial to the healthy development of the girls in the community.

Objectives The ways in which children understand dying and death remain poorly understood; most studies have been carried out with samples other than persons with an illness. The objective of this study was to understand the process by which children directly involved with life-limiting conditions understand dying and death. Methods This qualitative study obtained interview data from N = 44 5–18-year-old children in the USA, Haiti, and Uganda who were pediatric palliative care patients or siblings of patients. Of these, 32 were children with a serious condition and 12 were siblings of a child with a serious condition. Interviews were recorded, transcribed, verified, and analyzed using grounded theory methodology. Results Loss of normalcy and of relationships emerged as central themes described by both ill children and siblings. Resilience, altruism, and spirituality had a bidirectional relationship with loss, being strategies to manage both losses and anticipated death, but also being affected by losses. Resiliency and spirituality, but not altruism, had a bidirectional relationship with anticipating death. Themes were consistent across the 3 samples, although the beliefs and behaviors expressing them varied by country. Significance of results This study partially fills an identified gap in research knowledge about ways in which children in 3 nations understand dying and death. While children often lack an adult vocabulary to express thoughts about dying and death, results show that they are thinking about these topics. A proactive approach to address issues is warranted, and the data identify themes of concern to children.