Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

Effective control of pathogens is typically achieved by the timely interplay between the innate and adaptive immune response of an individual..

Design Principles for Online Platforms Fostering Deliberative Political Discourse

The design choices behind participatory platforms, intended to facilitate interaction between citizens and government representatives, frequently undermine the potential for genuine democratic deliberation. This article presents a set of six success criteria for publicly owned online participatory platforms designed to facilitate the process of deliberation: political privacy, discursive diversity, reciprocity, reflexivity, availability of information, and perceived impact. In addition, 12 design principles that support these success criteria are formulated, whose use might increase the effective implementation and take-up of online participatory platforms fostering democratic deliberation

The burden of self-reported antibiotic allergies in health care and how to address it: A systematic review of the evidence

Background: Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased antimicrobial resistance. Unconfirmed reported antibiotic allergy labels create a significant barrier to optimal antimicrobial stewardship in health care, with clinical and economic implications. Objective: A systematic review was conducted to summarize the impact of patient-reported antibiotic allergy on clinical outcomes and various strategies that have been employed to effectively assess and remove these allergy labels, improving patient care. Methods: The review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A critical appraisal was conducted on all studies and a narrative synthesis was performed to identify themes. Results: Four themes emerged: the prevalence of antibiotic allergy, impact of antibiotic allergy on antimicrobial prescribing, impact of antibiotic allergy on clinical outcomes, and delabeling strategies to improve clinical outcomes. Of the 32 studies, including 1,089,675 participants, the prevalence of reported antibiotic allergy was between 5% and 35%. Patients with a reported antibiotic allergy had poorer concordance with prescribing guidelines in 30% to 60% of cases, with a higher use of alternatives such as quinolone, tetracycline, macrolide, lincosamide, and carbapenem and lower use of beta-lactam antibiotics. Antibiotic allergy delabeling was identified as an intervention and recommendation to advance the state of the science. Conclusions: There is substantial evidence within the literature that antibiotic allergy labels significantly impact patient clinical outcomes and a consensus that systematic assessment of reported antibiotic allergies, commonly referred to as delabeling, improves the clinical management of patients

Asthma Predictors Influence on Self-management Asthma Education Status

ObjectiveThe objective of this study was to determine the characteristics of adults with active asthma who were most likely to acquire self-management asthma component education.MethodsWe analyzed adult data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS)-Asthma Call-back Survey (ACBS). Multivariate logistic regression and multivariate linear regression models were used to analyze the association between asthma self-management education and predictors.ResultsAdults who had health insurance (aB = 0.33 [SE = 0.15], p \u3c .05), routine care visits (aB = 0.75 [SE = 0.08], p \u3c .05) and hospitalization (aB = 0.50 [SE = 0.23], p \u3c .05) reported higher asthma education scores. Adults aged 18-34 years were more likely to report inhaler use instruction (aOR = 3.9; 95% CI: 2.5-6.3, p \u3c .05), than older adults aged 65 years and older. Having a formal education, being a woman, and being black increased the likelihood of having a higher self-management score.ConclusionHaving health insurance, making routine visits, and having asthma episodes were associated with multiple asthma education components which ensures social justice. Asthma control programs need to reexamine asthma education components to make sure they are promoted to persons regardless of their age, education level, or sex.

Prospects for clinical use of reprogrammed cells for autologous treatment of macular degeneration

Since the discovery of induced pluripotent stem cells (iPSC) in 2006, the symptoms of many human diseases have been reversed in animal models with iPSC therapy, setting the stage for future clinical development. From the animal data it is clear that iPSC are rapidly becoming the lead cell type for cell replacement therapy and for the newly developing field of iPSC-derived body organ transplantation. The first human pathology that might be treated in the near future with iPSC is age-related macular degeneration (AMD), which has recently passed the criteria set down by regulators for phase I clinical trials with allogeneic human embryonic stem cell-derived cell transplantation in humans. Given that iPSC are currently in clinical trial in Japan (RIKEN) to treat AMD, the establishment of a set of international criteria to make clinical-grade iPSC and their differentiated progeny is the next step in order to prepare for future autologous cell therapy clinical trials. Armed with clinical-grade iPSC, we can then specifically test for their threat of cancer, for proper and efficient differentiation to the correct cell type to treat human disease and then to determine their immunogenicity. Such a rigorous approach sets a far more relevant paradigm for their intended future use than non-clinical-grade iPSC. This review focuses on the latest developments regarding the first possible use of iPSC-derived retinal pigment epithelial cells in treating human disease, covers data gathered on animal models to date and methods to make clinical-grade iPSC, suggests techniques to ensure quality control and discusses possible clinical immune responses

The possible future roles for IPSC-Derived therapy for Autoimmune Diseases.

The ability to generate inducible pluripotent stem cells (iPSCs) and the potential for their use in treatment of human disease is of immense interest. Autoimmune diseases, with their limited treatment choices are a potential target for the clinical application of stem cell and iPSC technology. IPSCs provide three potential ways of treating autoimmune disease; (i) providing pure replacement of lost cells (immuno-reconstitution); (ii) through immune-modulation of the disease process in vivo; and (iii) for the purposes of disease modeling in vitro. In this review, we will use examples of systemic, system-specific and organ-specific autoimmunity to explore the potential applications of iPSCs for treatment of autoimmune diseases and review the evidence of iPSC technology in auto-immunity to date

An Approach to Mapping Forest Growth Stages in Queensland, Australia through Integration of ALOS PALSAR and Landsat Sensor Data

Whilst extensive clearance of forests in the eastern Australian Brigalow Belt Bioregion (BBB) has occurred since European settlement, appropriate management of those that are regenerating can facilitate restoration of biomass (carbon) and biodiversity to levels typical of relatively undisturbed or remnant formations. However, maps of forests are different stages of regeneration are needed to facilitate restoration planning, including prevention of further re-clearing. Focusing on the Tara Downs subregion of the BBB and on forests with brigalow (Acacia harpophylla) as a component, this research establishes a method for differentiating and mapping early, intermediate and remnant growth stages from Japan Aerospace Exploration Agency (JAXA) Advanced Land Observing Satellite (ALOS) Phased-Array L-band Synthetic Aperture Radar (PALSAR) Fine Beam Dual (FBD) L-band HH- and HV-polarisation backscatter and Landsat-derived Foliage Projective Cover (FPC). Using inventory data collected from 74 plots, located in the Tara Downs subregion, forests were assigned to one of three regrowth stages based on their height and cover relative to that of undisturbed stands. The image data were then segmented into objects with each assigned to a growth stage by comparing the distributions of L-band HV and HH polarisation backscatter and FPC to that of reference distributions using a z-test. Comparison with independent assessments of growth stage, based on time-series analysis of aerial photography and SPOT images, established an overall accuracy of > 70%, with this increasing to 90% when intermediate regrowth was excluded and only early-stage regrowth and remnant classes were considered. The proposed method can be adapted to respond to amendments to user-definitions of growth stage and, as regional mosaics of ALOS PALSAR and Landsat FPC are available for Queensland, has application across the state

Second generation 4,5,6,7-tetrahydrobenzo[d]thiazoles as novel DNA gyrase inhibitors

Aim: DNA gyrase and topoisomerase IV are essential bacterial enzymes, and in the fight against bacterial resistance, they are important targets for the development of novel antibacterial drugs. Results: Building from our first generation of 4,5,6,7-tetrahydrobenzo[d]thiazole-based DNA gyrase inhibitors, we designed and prepared an optimized series of analogs that show improved inhibition of DNA gyrase and topoisomerase IV from Staphylococcus aureus and Escherichia coli, with IC50 values in the nanomolar range. Importantly, these inhibitors also show improved antibacterial activity against Gram-positive strains. Conclusion: The most promising inhibitor, 29, is active against Enterococcus faecalis, Enterococcus faecium and S. aureus wild-type and resistant strains, with minimum inhibitory concentrations between 4 and 8 mu g/ml, which represents good starting point for development of novel antibacterials. Graphical abstractPeer reviewe

CD8 Epitope Escape and Reversion in Acute HCV Infection

In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70–80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8–restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon γ enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8–associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution