Hepatitis C virus (HCV) isHepatitis C virus (HCV) is a leading cause of chronic liver disease, which affects around 170 million people worldwide. Infections are initially acute, and in many cases the symptoms are mild. However, around 80% of patients eventually develop a persistent chronic infection which can result in steatosis, fibrosis, cirrhosis, liver failure, and, in some cases, hepatocellular carcinoma. The main treatments currently available for chronically infected patients use a combination of pegylated alpha interferon and ribavirin, but these still result in a sustained antiviral response in only about 50% of genotype 1 infections (4). Consequently, more effective antivirals that target either the virus proteins directly or the host cell proteins required during HCV replication are currently being developed. In order to ensure that successful antivirals are generated, it is important that all aspects of the HCV life cycle and HCV-associated pathology are well understood.One way in which the different host processes that are an essential part of the HCV replication cycle can be studied is to investigate the effect that HCV infection has on cellular gene expression. RNA microarray hybridization is routinely used to investigate host gene expression and allows the entire transcriptomic profile of the cell to be characterized. Microarray analysis of HCV-infected cells can provide an insight into the genes involved in host cell antiviral responses, genes that are essential for the HCV replication cycle, and genes that contribute to HCV-associated liver pathology. Microarray expression profiling has already been used to study host gene expression in cells transfected with RNA encoding either individual HCV genes, HCV subgenomic replicons, or the full-length HCV genome. These studies have demonstrated that the replication of the HCV genome results in the regulation of a small number of host genes involved in lipid metabolism, cellular immunity, proliferation, apoptosis, and molecular transport (2,5,15,32). These studies have provided interesting insights into the HCV replication cycle. However, the biological significance of gene expression patterns identified is less clear, since the full virus replication cycle, including the processes of viral entry, assembly, and exit, does not take place.The recent discovery of JFH-1, a genotype 2a HCV clone that can undergo a complete infection cycle in cell culture, provides the opportunity to characterize the true effect of HCV infection on host gene expression (51). A recent study investigated the effects that a J6/JFH-1 chimera had on the gene expression profile of Huh7.5 cells during a time course infection with time points of 24, 48, 72, 96, and 120 h (53). The number of host genes regulated during infection was much higher than that previously observed for cells permitting only genome replication, indicating that the full replication cycle has additional effects on host gene expression.In this study, we present the results from an investigation

Much of the knowledge about the relationships among domains of psychopathology is built on the diagnostic categories described in the Diagnostic and Statistical Manual of Mental Disorders ( DSM), and relatively little research has examined the symptom-level structure of psychopathology. The aim of this study was to delineate a detailed hierarchical model of psychopathology—from individual symptoms up to a general factor of psychopathology—allowing both higher- and lower-order dimensions to depart from the structure of the DSM. We explored the hierarchical structure of hundreds of symptoms spanning 18 DSM disorders in two large samples—one from the general population in Australia ( n = 3,175) and the other a treatment-seeking clinical sample from the United States ( n = 1,775). There was marked convergence between the two samples, offering new perspectives on higher-order dimensions of psychopathology. We also found several noteworthy departures from the structure of the DSM in the symptom-level data.

Baclofen may be an effective treatment option for patients with ALD. However, given the profile of adverse events, the role for this medication might be best limited to specialist services.Declaration of interestNone.

Background: The dissemination and adoption of research into clinical practice in health care settings is a complex and challenging process. Clinical champions have been increasingly used in health care to facilitate the implementation and adoption of evidence-based practice and to overcome organizational barriers. In relation to substance use and mental health disorders, translation of new evidence into practice is an ongoing challenge. The utilization of a clinical champion to motivate staff to implement evidence-based practice in these settings may improve treatment quality and reduce the burden of disease. We thus aimed to conduct a systematic review to examine the role and efficacy of clinical champions in the drug and alcohol and mental health settings. Methods: We conducted a systematic literature search (1980-present) using the following databases: PubMed and PsycINFO. Additional studies were identified using reference searches of relevant reviews. Results: Thirteen separate studies were included in the final review. Clinical champions were typically selected rather than emergent, including clinical staff members engaging in a professional clinical role (e.g., physicians, psychologists, social workers). Training provided for these roles was often not stated. Clinical champions assisted with faster initiation and persistence in the application of novel interventions, facilitating overcoming system barriers, and enhanced staff engagement and motivation. Conclusions: In the substance use and mental health field, clinical champions appear to be an important component to facilitating practice changes. Future studies should provide specific details regarding attributes and training and also examine the relevant combination of personal characteristics and training sufficient to facilitate implementation of evidence-based practice in drug and alcohol and mental health settings. Plain language abstract Treatment delivery in drug and alcohol and mental health settings may not always be based on best available evidence. Organizational context and individual factors are important in determining whether new practices will be adopted. Passive approaches such as websites or treatment manuals do not necessarily lead to change in practice. The clinical champion model has been shown to be effective in aiding implementation of evidence-based practice in health care settings. However, there is limited evidence evaluating its use in drug and alcohol and mental health settings. The current review aims to synthesize and evaluate the use of clinical champions in implementation research in drug and alcohol and mental health settings. We found that clinical champions were typically clinical staff members engaging in a professional clinical role. Training provided for these roles was often limited. Clinical champions may assist with faster initiation and persistence in the application of novel interventions, facilitating overcoming system barriers, and enhanced staff engagement and motivation.

BackgroundTapeworms are agents of neglected tropical diseases responsible for significant health problems and economic loss. They also exhibit adaptations to a parasitic lifestyle that confound comparisons of their development with other animals. Identifying the genetic factors regulating their complex ontogeny is essential to understanding unique aspects of their biology and for advancing novel therapeutics. Here we use RNA sequencing to identify up-regulated signalling components, transcription factors and post-transcriptional/translational regulators (genes of interest, GOI) in the transcriptomes of Larvae and different regions of segmented worms in the tapeworm Hymenolepis microstoma and combine this with spatial gene expression analyses of a selection of genes.ResultsRNA-seq reads collectively mapped to 90% of the > 12,000 gene models in the H. microstoma v.2 genome assembly, demonstrating that the transcriptome profiles captured a high percentage of predicted genes. Contrasts made between the transcriptomes of Larvae and whole, adult worms, and between the Scolex-Neck, mature strobila and gravid strobila, resulted in 4.5–30% of the genes determined to be differentially expressed. Among these, we identified 190 unique GOI up-regulated in one or more contrasts, including a large range of zinc finger, homeobox and other transcription factors, components of Wnt, Notch, Hedgehog and TGF-β/BMP signalling, and post-transcriptional regulators (e.g. Boule, Pumilio). Heatmap clusterings based on overall expression and on select groups of genes representing ‘signals’ and ‘switches’ showed that expression in the Scolex-Neck region is more similar to that of Larvae than to the mature or gravid regions of the adult worm, which was further reflected in large overlap of up-regulated GOI.ConclusionsSpatial expression analyses in Larvae and adult worms corroborated inferences made from quantitative RNA-seq data and in most cases indicated consistency with canonical roles of the genes in other animals, including free-living flatworms. Recapitulation of developmental factors up-regulated during larval metamorphosis suggests that strobilar growth involves many of the same underlying gene regulatory networks despite the significant disparity in developmental outcomes. The majority of genes identified were investigated in tapeworms for the first time, setting the stage for advancing our understanding of developmental genetics in an important group of flatworm parasites.Electronic supplementary materialThe online version of this article (10.1186/s13227-018-0110-5) contains supplementary material, which is available to authorized users.

To assess beneficial and adverse effects of psychological treatment versus active alternative treatment or no treatment in adults with migraine, using methods that allow comparison with reviews of psychological interventions for other painful conditions.

Screening and assessment (Chapter 2): screening techniques to identify patients with alcohol problems, and subsequent assessments for clinicians to undertake before providing specific treatments or interventions.• Interventions, treatments, relapse prevention and aftercare (Chapter 3): a range of varying interventions and treatments, including brief interventions, brief e-health interventions, psychosocial interventions, alcohol withdrawal management, pharmacotherapy options, and peer support programs. In the final section of this chapter, relapse prevention, aftercare, and long term follow-up strategies are discussed.• Considerations for specific populations (Chapter 4): the management of alcohol problems and treatment considerations for specific population groups of interest in Australia -genderspecific considerations, adolescents and young people, pregnant and breastfeeding women, Aboriginal and Torres Strait Islander peoples, culturally and linguistically diverse groups, sexually diverse and gender diverse populations, older people, and cognitively impaired people.• Understanding comorbidities (Chapter 5): the importance of considering a range of comorbidities when providing treatment for alcohol problems. Polydrug use, comorbid mental disorders, and physical-related comorbidities are discussed.The content of this supplement is based on the various chapters of the full Guidelines for the Treatment of Alcohol Problems, which were based on reviews of the evidence, including well designed meta-analyses and randomised controlled trials, wherever possible. Where this evidence was not available, recommendations were based on the best available research or clinical experience. Each recommendation in the guidelines is accompanied with a level of evidence based on National Health and Medical Research Council evidence recommendations (Box 2), 21 with "A" representing the most evidence and "GPP" (good practice point) indicating a recommendation with no evidence.For more on the Guidelines for the Treatment of Alcohol Problems, visit https://alcoh oltre atmen tguid elines.com.au/. Acknowledgements:The Guidelines for the Treatment of Alcohol Problems project was funded by the Australian Government, under the Drug and Alcohol Program. We would like to express our gratitude to members of the Guidelines Steering Committee for providing invaluable guidance and advice on this project. We thank Daniel Winter, Sophia Little, Brennan Geiger and James Pham for providing research and administrative support, and Joshua Watt for providing clinical support, across sections of this supplement. Finally, we thank Donna Ah Chee, Kylie Lee, Teagan Weatherall, Craig Holloway and Martin Nean for conversations and work which informed the Aboriginal and Torres Strait Islander peoples section in the guidelines and Chapter 4 of this supplement.Competing interests: Paul Haber has been funded by the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney to undertake clinical trials of cannabinoid treatment for alcohol withdra...

The BDEPQ was found to be a reliable and valid self-report instrument for the assessment of BZD dependence in samples approximating the general population of people using BZDs.