Lysosomotropic agents as HCV entry inhibitors

HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH4Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

Economic Evaluations of Occupational Health Interventions from a Company’s Perspective: A Systematic Review of Methods to Estimate the Cost of Health-Related Productivity Loss

Objectives: To investigate the methods used to estimate the indirect costs of health-related productivity in economic evaluations from a company’s perspective. Methods: The primary literature search was conducted in Medline and Embase. Supplemental searches were conducted in the Cochrane NHS Economic Evaluation Database, the National Institute for Occupational Safety and Health database, the Ryerson International Labour, Occupational Safety and Health Index database, scans of reference lists and researcher’s own literature database. Article selection was conducted independently by two researchers based on title, keywords, and abstract, and if needed, full text. Differences were resolved by a consensus procedure. Articles were selected based on seven criteria addressing study population, type of intervention, comparative intervention, outcome, costs, language and perspective, respectively. Characteristics of the measurement and valuation of health-related productivity were extracted and analyzed descriptively. Results: A total of 34 studies were included. Costs of health-related productivity were estimated using (a combination of) data related to sick leave, compensated sick leave, light or modified duty or work presenteeism. Data were collected from different sources (e.g. administrative databases, worker self-report, supervisors) and by different methods (e.g. questionnaires, interviews). Valuation varied in terms of reported time units, composition and source of the corresponding price weights, and whether additional elements, such as replacement costs, were included. Conclusions: Methods for measuring and valuing health-related productivity vary widely, hindering comparability of results and decision-making. We provide suggestions for improvement

The Distressed Brain: A Group Blind Source Separation Analysis on Tinnitus

Background: Tinnitus, the perception of a sound without an external sound source, can lead to variable amounts of distress. Methodology: In a group of tinnitus patients with variable amounts of tinnitus related distress, as measured by the Tinnitus Questionnaire (TQ), an electroencephalography (EEG) is performed, evaluating the patients ’ resting state electrical brain activity. This resting state electrical activity is compared with a control group and between patients with low (N = 30) and high distress (N = 25). The groups are homogeneous for tinnitus type, tinnitus duration or tinnitus laterality. A group blind source separation (BSS) analysis is performed using a large normative sample (N = 84), generating seven normative components to which high and low tinnitus patients are compared. A correlation analysis of the obtained normative components ’ relative power and distress is performed. Furthermore, the functional connectivity as reflected by lagged phase synchronization is analyzed between the brain areas defined by the components. Finally, a group BSS analysis on the Tinnitus group as a whole is performed. Conclusions: Tinnitus can be characterized by at least four BSS components, two of which are posterior cingulate based, one based on the subgenual anterior cingulate and one based on the parahippocampus. Only the subgenual component correlates with distress. When performed on a normative sample, group BSS reveals that distress is characterized by two anterior cingulate based components. Spectral analysis of these components demonstrates that distress in tinnitus is relate