Viral kinetics of the Hepatitis C virus

Hepatitis A virus and hepatitis B virus were identified as the cause of infectious hepatitis and serum hepatitis respectively in the beginning of the seventies. After introduction of screening tests for hepatitis A and B 4 only 25% of the cases of post transfusion hepatitis were found to be caused by hepatitis B and none by hepatitis A. One or more viruses other than hepatitis A or B were suspected to be the cause of the remaining 75% of post-transfusion hepatitis. Initially, this hepatitis was named non-A, non-B hepatitis. After the discovery in 1989 of the hepatitis C virus (HCV), HCV was found to explain the large majority of post transfusion hepatitis 5,6. HCV is an enveloped, s'mgle-stranded RNA virus, approximately 50 nm in diameter, that has been classified as a separate genus in the Flaviviridae family J Occasionally acute viral hepatitis with jaundice occurs, but usually HCV presents as chronic hepatitis. In fact it appeared to be the most important causes of chronic viral hepatitis in Europe and the United States

Spatial and environmental assessment of energy potentials for Anaerobic Digestion production systems applied to the Netherlands

Anaerobic digestion (AD) can play an important role in achieving the renewable energy goals set within the European Union. Within this article the focus is placed on reaching the Dutch local renewable production goal set for the year 2020 with locally available biomass waste flows, avoiding intensive farming and long transport distances of biomass and energy carriers. The bio-energy yields, efficiency and environmental sustainability are analyzed for five municipalities in the northern part of the Netherlands, using three utilization pathways: green gas production, combined heat and power, and waste management. Literature has indicated that there is sufficient bio-energy potential in local waste streams to reach the aforementioned goal. However, the average useful energy finally produced by the AD production pathway is significantly lower, often due to poor quality biomass and difficult harvesting conditions. Furthermore, of the potential bio-energy input in the three utilization pathways considered in this article, on average: 73% can be extracted as green gas; 57% as heat and power; and 44% as green gas in the waste management pathway. This demonstrates that the Dutch renewable production goal cannot be reached. The green gas utilization pathway is preferable for reaching production goals as it retains the highest amount of energy from the feedstock. However, environmental sustainability favors the waste management pathway as it has a higher overall efficiency, and lower emissions and environmental impacts. The main lessons drawn from the aforementioned are twofold: there is a substantial gap between bio-energy potential and net energy gain; there is also a gap between top-down regulation and actual emission reduction and sustainability. Therefore, a full life cycle-based understanding of the absolute energy and environmental impact of biogas production and utilization pathways is required to help governments to develop optimal policies serving a broad set of sustainable objectives. Well-founded ideas and decisions are needed on how best to utilize the limited biomass availability most effectively and sustainably in the near and far future, as biogas can play a supportive role for integrating other renewable sources into local decentralized energy systems as a flexible and storable energy source. (C) 2016 Elsevier Ltd. All rights reserved

Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis C patients: a case control study

BACKGROUND: High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied. METHODS: A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction. RESULTS: Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group. CONCLUSIONS: These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C

Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study

BACKGROUND: High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied. METHODS: A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction. RESULTS: Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group. CONCLUSIONS: These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C

Epidemiology of chronic pain in the Netherlands

Chronic pain is very common but good data are scarce about the prevalence, incidence, diagnosis, severity, treatment, utilization of health care, and the impact of chronic pain on society, health care systems and the patient. Information about the epidemiology of chronic pain can help decision and policy makers decide about health budgets and prioritization, patient segmenting and budget fencing, and therapy budgets, including behavioural therapy and drug budgets. This report aims to provide epidemiological information about chronic pain in the Netherlands using the most representative, recent, comprehensive and valid studies. Out of 16 619 retrieved titles and abstracts, we selected 155 studies from the Netherlands that were relevant to the project questions. From these, we selected at least three studies per question that provided the most recent, representative and valid data

An integrated approach for the validation of energy and environmental system analysis models:used in the validation of the Flexigas Excel BioGas model

A review has been completed for a verification and validation (V&V) of the (Excel) BioGas simulator or EBS model. The EBS model calculates the environmental impact of biogas production pathways using Material and Energy Flow Analysis, time dependent dynamics, geographic information, and Life Cycle analysis. Within this article a V&V method is researched, selected and applied to validate the EBS model. Through the use of the method described within this article: mistakes in the model are resolved, the strengths and weaknesses of the model are found, and the concept of the model is tested and strengthened. The validation process does not only improve the model but also helps the modelers in widening their focus and scope. This article can, therefore, also be used in the validation process of similar models. The main result from the V&V process indicates that the EBS model is valid; however, it should be considered as an expert model and should only be used by expert users

Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity

Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to β-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by β-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues

Electrophysiological correlates of error monitoring and feedback processing in second language learning

Humans monitor their behavior to optimize performance, which presumably relies on stable representations of correct responses. During second language (L2) learning, however, stable representations have yet to be formed while knowledge of the first language (L1) can interfere with learning, which in some cases results in persistent errors. In order to examine how correct L2 representations are stabilized, this study examined performance monitoring in the learning process of second language learners for a feature that conflicts with their first language. Using EEG, we investigated if L2 learners in a feedback-guided word gender assignment task showed signs of error detection in the form of an error-related negativity (ERN) before and after receiving feedback, and how feedback is processed. The results indicated that initially, response-locked negativities for correct (CRN) and incorrect (ERN) responses were of similar size, showing a lack of internal error detection when L2 representations are unstable. As behavioral performance improved following feedback, the ERN became larger than the CRN, pointing to the first signs of successful error detection. Additionally, we observed a second negativity following the ERN/CRN components, the amplitude of which followed a similar pattern as the previous negativities. Feedback-locked data indicated robust FRN and P300 effects in response to negative feedback across different rounds, demonstrating that feedback remained important in order to update memory representations during learning. We thus show that initially, L2 representations may often not be stable enough to warrant successful error monitoring, but can be stabilized through repeated feedback, which means that the brain is able to overcome L1 interference, and can learn to detect errors internally after a short training session. The results contribute a different perspective to the discussion on changes in ERN and FRN components in relation to learning, by extending the investigation of these effects to the language learning domain. Furthermore, these findings provide a further characterization of the online learning process of L2 learners