Effect of ribavirin on the hepatitis C virus (JFH-1) and its correlation with interferon sensitivity

BACKGROUND: The consensus therapy for chronic hepatitis C infection is based on a synergistic combination of pegylated interferon and ribavirin. The therapy leads to a sustained virological response in around 60% of infected patients. The mechanism by which this synergy occurs has not yet been elucidated. Several mechanisms of action have been proposed; one suggests that ribavirin, which is a nucleoside analogue, is incorporated into the RNA strand and generates an increase in the error rate. Such an accumulation of mutations would threaten the integrity of the virus's genetic information. METHODS: The effects of ribavirin on the new infectious hepatitis C virus cell culture (HCVcc) system were investigated using Huh-7 cells. Cells were cultured for 1 month in either 0 microM, 20 microM or 50 microM ribavirin. The HCV interferon sensitivity and the NS5A quasispecies were analysed. RESULTS: An increase in the mutation rate in the HCV NS5A gene was observed when the infected cells were treated with 50 microM ribavirin for 1 month. Amino acid sequence analysis revealed that ribavirin exerts an increase in G to A transition events as predicted by its mutagenic effect and a selective pressure on the HCV NS5A sequence. Furthermore, ribavirin treatment modified the efficacy of interferon (IFN) treatment. The IFN half-inhibition concentration (IC50) was significantly lower for viruses obtained after 1 month's exposure to 50 microM ribavirin than for viruses cultured in the absence of ribavirin. CONCLUSIONS: Ribavirin's mutagenic effect could explain in part its synergistic action with interferon.     

Spatio-temporal monitoring by ground-based and air- and space-borne lidars of a moderate Saharan dust event affecting southern Europe in June 2013 in the framework of the ADRIMED/ChArMEx campaign

During the ADRIMED (Aerosol Direct Radiative Impact on the regional climate in the Mediterranean region) special observation period (SOP-1a), conducted in June 2013 in the framework of the ChArMEx (Chemistry-Aerosol Mediterranean Experiment) project, a moderate Saharan dust event swept the Western and Central Mediterranean Basin (WCMB) from west to east during a 9-day period between 16 and 24 June. This event was monitored from the ground by six EARLINET/ACTRIS (European Aerosol Research Lidar Network/Aerosols, Clouds, and Trace gases Research Infrastructure Network) lidar stations (Granada, Barcelona, Naples, Potenza, Lecce and Serra la Nave) and two ADRIMED/ChArMEx lidar stations specially deployed for the field campaign in Cap d’en Font and Ersa, in Minorca and Corsica Islands, respectively. The first part of the study shows the spatio-temporal monitoring of the dust event during its transport over the WCMB with ground-based lidar and co-located AERONET (Aerosol Robotic Network) Sun-photometer measurements. Dust layer optical depths, Ångström exponents, coarse mode fractions, linear particle depolarization ratios (LPDRs), dust layer heights and the dust radiative forcing estimated in the shortwave (SW) and longwave (LW) spectral ranges at the bottom of the atmosphere (BOA) and at the top of the atmosphere (TOA) with the Global Atmospheric Model (GAME), have been used to characterize the dust event. Peak values of the AERONET aerosol optical depth (AOD) at 440 nm ranged between 0.16 in Potenza and 0.37 in Cap d’en Font. The associated Ångström exponent and coarse mode fraction mean values ranged from 0.43 to 1.26 and from 0.25 to 0.51, respectively. The mineral dust produced a negative SW direct radiative forcing at the BOA ranging from ?56.9 to ?3.5 W m^?2. The LW radiative forcing at the BOA was positive, ranging between +0.3 and +17.7 W m^-2. The BOA radiative forcing estimates agree with the ones reported in the literature. At the TOA, the SW forcing varied between ?34.5 and +7.5 W m^?2. In seven cases, the forcing at the TOA resulted positive because of the aerosol strong absorbing properties (0.83 < single-scattering albedo (SSA) < 0.96). The multi-intrusion aspect of the event is examined by means of air- and space-borne lidar measurements, satellite images and back trajectories. The analysis reported in this paper underline the arrival of a second different intrusion of mineral dust observed over southern Italy at the end of the considered period which probably results in the observed heterogeneity in the dust properties.     

Efficacy of Low-Level Laser Therapy for Body Contouring and Spot Fat Reduction

Background  

Low-level laser therapy (LLLT) is commonly used in medical applications, but scientific studies of its efficacy and the mechanism by which it causes loss of fat from fat cells for body contouring are lacking. This study examined the effectiveness and mechanism by which 635–680 nm LLLT acts as a non-invasive body contouring intervention method.     

Hepatitis C virus proteins

Hepatitis C virus (HCV) encodes a single polyprotein, which is processed by cellular and viral proteases to generate 10 polypeptides. The HCV genome also contains an overlapping +1 reading frame that may lead to the synthesis of an additional protein. Until recently, studies of HCV have been hampered by the lack of a productive cell culture system. Since the identification of HCV genome approximately 17 years ago, structural, biochemical and biological information on HCV proteins has mainly been obtained with proteins produced by heterologous expression systems. In addition, some functional studies have also been confirmed with replicon systems or with retroviral particles pseudotyped with HCV envelope glycoproteins. The data that have accumulated on HCV proteins begin to provide a framework for understanding the molecular mechanisms involved in the major steps of HCV life cycle. Moreover, the knowledge accumulated on HCV proteins is also leading to the development of antiviral drugs among which some are showing promising results in early- phase clinical trials. This review summarizes the current knowledge on the functions and biochemical features of HCV proteins.     

Presurgical diagnosis of posterior deep infiltrating endometriosis based on a standardized questionnaire

BACKGROUND: To derive a diagnostic model based on symptoms and history as assessed by a standardized questionnaire to predict posterior deep infiltrating endometriosis (DIE) among women with chronic pelvic pain symptoms. METHODS: 134 women scheduled for laparoscopy for chronic pelvic pain symptoms completed a standardized self-administered questionnaire, specifically designed for the study. We compared the symptoms of the women with posterior DIE diagnosed at laparoscopy with those of the women with other disorders, and used multiple logistic regression analysis to select the best combination of symptoms for predicting posterior DIE. Cross-validation was performed with the jackknife method. RESULTS: 51 women (38.1%) were diagnosed with posterior DIE and 83 with other disorders (61.9%). The following variables were independent predictors for posterior DIE: painful defecation during menses, severe dyspareunia (visual analogic scale > or =8), pain other than noncyclic, and previous surgery for endometriosis. The cross-validation procedure leads to a simplified diagnostic model that uses two independent predictors: painful defecation during menses and severe dyspareunia. The sensitivity of this model for diagnosing posterior DIE was 74.5%, its specificity was 68.7%, its positive likelihood ratio was 2.4, and its negative likelihood ratio was 0.4. It correctly classified 70.9% of our sample into a high-risk (with either severe dyspareunia or painful defecation during menses) and a low-risk (neither symptom) group. CONCLUSIONS: Standardized evaluation of painful symptoms is useful for screening women so that they may have adequate exploration and counselling before laparoscopic surgery for pelvic pain symptoms.