bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus
Authors: Drappier Melissa , Opperdoes Fred R. , Michiels Thomas 
Published: April 2017

ABSTRACT
Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV.

IMPORTANCE
Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species
Theilovirus
includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L, indicating that this virus originates from mice.
Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection
Authors: Ivinson Karen , Deliyannis Georgia , McNabb Leanne , Grollo Lara , Gilbertson Brad , Jackson David , Brown Lorena E. 
Published: April 2017

ABSTRACTIt is possible to model the progression of influenza virus from the upper respiratory tract to the lower respiratory tract in the mouse using viral inoculum delivered in a restricted manner to the nose. In this model, infection with the A/Udorn/307/72 (Udorn) strain of virus results ultimately in high viral titers in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8) strain causes an infection that is almost entirely limited to the nasal passages. The factors that govern the progression of virus down the respiratory tract are not well understood. Here, we show that, while PR8 virus grows to high titers in the nose, an inhibitor present in the saliva blocks further progression of infection to the trachea and lungs and renders an otherwise lethal dose of virus completely asymptomatic.In vitro, the salivary inhibitor was capable of potent neutralization of PR8 virus and an additional 20 strains of type A virus and two type B strains that were tested. The exceptions were Udorn virus and the closely related H3N2 strains A/Port Chalmers/1/73 and A/Victoria/3/75. Characterization of the salivary inhibitor showed it to be independent of sialic acid and other carbohydrates for its function. This and other biochemical properties, together with its virus strain specificity andin vivofunction, indicate that the mouse salivary inhibitor is a previously undescribed innate inhibitory molecule that may have evolved to provide pulmonary protection of the species from fatal influenza virus infection.IMPORTANCEInfluenza A virus occasionally jumps from aquatic birds, its natural host, into mammals to cause outbreaks of varying severity, including pandemics in humans. Despite the laboratory mouse being used as a model to study influenza virus pathogenesis, natural outbreaks of influenza have not been reported in the species. Here, we shed light on one mechanism that might allow mice to be protected from influenza in the wild. We show that virus deposited in the mouse upper respiratory tract will not progress to the lower respiratory tract due to the presence of a potent inhibitor of the virus in saliva. Containing inhibitor-sensitive virus to the upper respiratory tract renders an otherwise lethal infection subclinical. This knowledge sheds light on how natural inhibitors may have evolved to improve survival in this species.
Central Nervous System Infection with Borna Disease Virus Causes Kynurenine Pathway Dysregulation and Neurotoxic Quinolinic Acid Production
Authors: Formisano Simone , Hornig Mady , Yaddanapudi Kavitha , Vasishtha Mansi , Parsons Loren H. , Briese Thomas , Lipkin W. Ian , Williams Brent L. 
Published: April 2017

ABSTRACT

Central nervous system infection of neonatal and adult rats with Borna disease virus (BDV) results in neuronal destruction and behavioral abnormalities with differential immune-mediated involvement. Neuroactive metabolites generated from the kynurenine pathway of tryptophan degradation have been implicated in several human neurodegenerative disorders. Here, we report that brain expression of key enzymes in the kynurenine pathway are significantly, but differentially, altered in neonatal and adult rats with BDV infection. Gene expression analysis of rat brains following neonatal infection showed increased expression of kynurenine amino transferase II (KATII) and kynurenine-3-monooxygenase (KMO) enzymes. Additionally, indoleamine 2,3-dioxygenase (IDO) expression was only modestly increased in a brain region- and time-dependent manner in neonatally infected rats; however, its expression was highly increased in adult infected rats. The most dramatic impact on gene expression was seen for KMO, whose activity promotes the production of neurotoxic quinolinic acid. KMO expression was persistently elevated in brain regions of both newborn and adult BDV-infected rats, with increases reaching up to 86-fold. KMO protein levels were increased in neonatally infected rats and colocalized with neurons, the primary target cells of BDV infection. Furthermore, quinolinic acid was elevated in neonatally infected rat brains. We further demonstrate increased expression of KATII and KMO, but not IDO,
in vitro
in BDV-infected C6 astroglioma cells. Our results suggest that BDV directly impacts the kynurenine pathway, an effect that may be exacerbated by inflammatory responses in immunocompetent hosts. Thus, experimental models of BDV infection may provide new tools for discriminating virus-mediated from immune-mediated impacts on the kynurenine pathway and their relative contribution to neurodegeneration.

IMPORTANCE
BDV causes persistent, noncytopathic infection
in vitro
yet still elicits widespread neurodegeneration of infected neurons in both immunoincompetent and immunocompetent hosts. Here, we show that BDV infection induces expression of key enzymes of the kynurenine pathway in brains of newborn and adult infected rats and cultured astroglioma cells, shunting tryptophan degradation toward the production of neurotoxic quinolinic acid. Thus, our findings newly implicate this metabolic pathway in BDV-induced neurodegeneration. Given the importance of the kynurenine pathway in a wide range of human infections and neurodegenerative and neuropsychiatric disorders, animal models of BDV infection may serve as important tools for contrasting direct viral and indirect antiviral immune-mediated impacts on kynurenine pathway dysregulation and the ensuing neurodevelopmental and neuropathological consequences.
The economic burden of physical inactivity: a systematic review and critical appraisal
Authors: Ding Ding , Kolbe-Alexander Tracy , Nguyen Binh , Katzmarzyk Peter T , Pratt Michael , Lawson Kenny D 
Published: April 2017

ObjectiveTo summarise the literature on the economic burden of physical inactivity in populations, with emphases on appraising the methodologies and providing recommendations for future studies.DesignSystematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number CRD42016047705).Data sourcesElectronic databases for peer-reviewed and grey literature were systematically searched, followed by reference searching and consultation with experts.Eligibility criteriaStudies that examined the economic consequences of physical inactivity in a population/population-based sample, with clearly stated methodologies and at least an abstract/summary written in English.ResultsOf the 40 eligible studies, 27 focused on direct healthcare costs only, 13 also estimated indirect costs and one study additionally estimated household costs. For direct costs, 23 studies used a population attributable fraction (PAF) approach with estimated healthcare costs attributable to physical inactivity ranging from 0.3% to 4.6% of national healthcare expenditure; 17 studies used an econometric approach, which tended to yield higher estimates than those using a PAF approach. For indirect costs, 10 studies used a human capital approach, two used a friction cost approach and one used a value of a statistical life approach. Overall, estimates varied substantially, even within the same country, depending on analytical approaches, time frame and other methodological considerations.ConclusionEstimating the economic burden of physical inactivity is an area of increasing importance that requires further development. There is a marked lack of consistency in methodological approaches and transparency of reporting. Future studies could benefit from cross-disciplinary collaborations involving economists and physical activity experts, taking a societal perspective and following best practices in conducting and reporting analysis, including accounting for potential confounding, reverse causality and comorbidity, applying discounting and sensitivity analysis, and reporting assumptions, limitations and justifications for approaches taken. We have adapted the Consolidated Health Economic Evaluation Reporting Standards checklist as a guide for future estimates of the economic burden of physical inactivity and other risk factors.
Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and NSTEMI Patients (PINPOINT): protocol for a prospective, observational, single-centre study
Authors: Adamski Piotr , Ostrowska Małgorzata , Sikora Joanna , Obońska Karolina , Buszko Katarzyna , Krintus Magdalena , Sypniewska Grażyna , Marszałł Michał Piotr , Koziński Marek , Kubica Jacek 
Published: April 2017

IntroductionThe most common classification of acute myocardial infarction (AMI) is based on electrocardiographic findings and distinguishes ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Both types of AMI differ concerning their epidemiology, clinical approach and early outcomes. Ticagrelor is a P2Y12 receptor inhibitor, constituting the first-line treatment for STEMI and NSTEMI. According to available data, STEMI may be associated with lower plasma concentration of ticagrelor in the first hours of AMI, but currently there are no studies directly comparing ticagrelor pharmacokinetics or antiplatelet effect in patients with STEMI versus NSTEMI.Methods and analysisThe PINPOINT study is a phase IV, single-centre, investigator-initiated, prospective, observational study designed to compare the pharmacokinetics and pharmacodynamics of ticagrelor in patients with STEMI and NSTEMI assigned to the invasive strategy of treatment. Based on an internal pilot study, the trial is expected to include at least 23 patients with each AMI type. All subjects will receive a 180 mg loading dose of ticagrelor. The primary end point of the study is the area under the plasma concentration-time curve (AUC(0–6)) for ticagrelor during the first 6 hours after the loading dose. Secondary end points include various pharmacokinetic features of ticagrelor and its active metabolite (AR-C124910XX), and evaluation of platelet reactivity by the vasodilator-stimulated phosphoprotein assay and multiple electrode aggregometry. Blood samples for the pharmacokinetic and pharmacodynamic assessment will be obtained at pretreatment, 30 min, 1, 2, 3, 4, 6 and 12 hours post-ticagrelor loading dose.Ethics and disseminationThe study received approval from the Local Ethics Committee (Komisja Bioetyczna Uniwersytetu Mikołaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy; approval reference number KB 617/2015). The study results will be disseminated through conference presentations and peer-reviewed journals.Trial registration numberNCT02602444; Pre-results.
Evaluation of the COPING parent online universal programme: study protocol for a pilot randomised controlled trial
Authors: Owen Dawn Adele , Griffith Nia , Hutchings Judy 
Published: April 2017

Trial sponsorBangor University, Brigantia Building, College Road, Bangor, LL57 2AS, UKIntroductionThe COPING parent online universal programme is a web-based parenting intervention for parents of children aged 3-8 years with an interest in positive parenting. The programme focuses on strengthening parent-child relationships and encouraging positive child behaviour. This trial will evaluate whether the intervention is effective in increasing the use of positive parenting strategies outlined in the programme using parent report and blind observation measures.Methods and analysisThis is a pilot randomised controlled trial with intervention and wait-list control conditions. The intervention is a 10-week online parenting programme to promote positive parent-child relations by teaching core social learning theory principles that encourage positive child behaviour, primarily through the use of praise and rewards. Health visitors and school nurses will circulate a recruitment poster to parents of children aged 3–8 years on their current caseloads. Recruitment posters will also be distributed via local primary schools and nurseries. Parents recruited to the trial will be randomised on a 2:1 ratio to intervention or wait-list control conditions (stratified according to child gender and age). The primary outcome measure is positive parenting as measured by a behavioural observation of parent-child interactions using the Dyadic Parent-Child Interaction Coding System. Secondary outcomes include parent report of child behaviour, and self-reported parental sense of competence, parenting behaviour and parental mental health. Data will be collected at baseline and 3 months later (postintervention) for all participants and 6 months postbaseline for the intervention group only. Analysis of covariance will be the main statistical method used.Ethics and disseminationThe trial has received ethical approval from the NHS Betsi Cadwaladr University Health Board Ethics Committee (REC) and the School of Psychology, Bangor University REC (15/WA/0463). Publication of all outcomes will be in peer-reviewed journals and conference presentations.Trial registration numberCurrent Controlled TrialsISRCTN89370147(5 May 2016).
Experiences, attitudes and possibilities for improvement concerning the cooperation between occupational physicians, rehabilitation physicians and general practitioners in Germany from the perspectives of the medical groups and rehabilitation patients – a protocol for a qualitative study
Authors: Voelter-Mahlknecht Susanne , Stratil Jan M , Kaluscha Rainer , Krischak Gert , Rieger Monika A 
Published: April 2017

IntroductionRehabilitation measures for patients in the working age primarily aim at maintaining employability, restoring fitness for work or timely return to work (RTW). To facilitate RTW after long sick leave in Germany, both rehabilitation physicians' knowledge about the patients' workplace and communication between the rehabilitation physician and the occupational physician need to be improved. This research will record the experiences and attitudes of occupational physicians, rehabilitation physicians and general practitioners, as well as of rehabilitation patients, to indicate barriers and possibilities for improvement concerning the intersection between workplace and rehabilitation institution. As a previous literature review has shown, insufficient data on the experiences and attitudes of the stakeholders are available. Therefore, an exploratory qualitative approach was chosen.Methods and analysis8 focus group discussions will be conducted with occupational physicians, rehabilitation physicians, general practitioners and rehabilitation patients (2 focus groups with 6–8 interviewees per category). Qualitative content analysis will be used to evaluate the data, thus describing positive and negative experiences and attitudes, barriers and possibilities for improvement at the intersection of general and occupational medicine and rehabilitation with regard to the workplace. The data from the focus groups will be used to develop a standardised quantitative questionnaire for a survey of the medical groups and rehabilitation patients in a follow-up project.Ethics and disseminationThe research will be undertaken with the approval of the Ethics Committee of the Medical Faculty and University Hospital of Tuebingen. The study participants’ consent will be documented in written form. The names of all study participants and all other confidential information data fall under medical confidentiality. The results will be published in a peer-reviewed medical journal independent of the nature of the results.
Impact of different dietary approaches on blood pressure in hypertensive and prehypertensive patients: protocol for a systematic review and network meta-analysis
Authors: Schwingshackl Lukas , Chaimani Anna , Hoffmann Georg , Schwedhelm Carolina , Boeing Heiner 
Published: April 2017

IntroductionLifestyle modification is one of the cornerstones in the management of hypertension. According to the most recent guidelines by the American Heart Association, all patients with hypertension should adopt the following dietary advices: increased consumption of fresh fruits, vegetables, low-fat dairy products and sodium reduction. The aim of the present study is to assess the efficacy of different dietary approaches on systolic and diastolic blood pressure in patients with hypertension and high normal blood pressure in a systematic review including a pairwise and network meta-analysis of randomised trials.Methods and analysisWe conducted searches in Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed and Google Scholar until November 2016. Citations, abstracts and relevant papers were screened for eligibility by two reviewers independently. Randomised trials were included if they met the following criteria: (1) hypertension (as mean values ≥140 mm Hg systolic blood pressure and/or ≥90 mm Hg diastolic blood pressure) or high normal blood pressure (mean systolic blood pressure ≥130 mm Hg and/or mean diastolic blood pressure ≥85 mm Hg), (2) age ≥18 years, (3) intervention diets (different type of dietary approaches, eg, dietary approach to stop hypertension diet; Mediterranean diet, vegetarian diet, palaeolithic diet, low sodium diet) either hypocaloric, isocaloric or ad libitum diets, (4) intervention period ≥12 weeks. For each outcome measure of interest, random effects pairwise and network meta-analyses were performed in order to determine the pooled relative effect of each intervention relative to every other intervention in terms of the postintervention values (or change scores). Subgroup analyses were planned for hypertensive status, study length, sample size, age and sex.Ethics and disseminationAs this study is based solely on the published literature, no ethics approval was required. We published our network meta-analysis in a peer-reviewed scientific journal.Systematic review registrationPROSPERO: CRD42016049243
Gout in primary care: Can we improve patient outcomes?
Authors: Callear Jacqueline , Blakey Georgina , Callear Alexandra , Sloan Linda 
Published: April 2017

In the United Kingdom, gout represents one of the most common inflammatory arthropathies predominantly managed in the primary care setting. Gout is a red flag indicator for cardiovascular disease and comorbidity. Despite this, there are no incentivised treatment protocols and suboptimal management in the primary care setting is common. A computer based retrospective search at a large inner city GP practice between January 2014-December 2014 inclusive, identified 115 patients with gout. Baseline measurements revealed multiple gout related consultations, poor medication compliance, high uric acid levels and deficiencies in uric acid monitoring.A series of improvement cycles were conducted. A telephone questionnaire conducted in January 2015, identified that patient education was suboptimal. The following improvement cycles aimed to educate patients, improve uric acid monitoring and support medication compliance. It was ultimately hoped that these measures would reduce gout flares and GP practice attendance. The improvement cycles contributed towards reduction in uric acid levels from 0.37 to 0.3 (p=0.14), 20% reduction in patients experiencing one or more gout flares and 77% reduction in GP related consultations between March 2015-March 2016 compared to baseline. The proportion of patients fully compliant with taking their urate lowering therapies improved from 63% to 91% (p=0.0001).A follow up series of PDSA cycles were performed between July-December 2016. The purpose of these cycles was to assess the sustainability of the improved medication compliance demonstrated by the improvement cycles. Three months following the completion of the improvement cycles, full medication compliance dropped from 91% to 70% (p=0.0001). The introduction of a paper calendar saw sustained and maintained improvement in medication compliance to 100% (p=0.0001) at the end of the study period. The improvement and PDSA cycles have demonstrated that simple interventions can be a sustainable way of improving disease control and patient outcomes.
Learning to swim: role of gender, age and practice in Latino children, ages 3–14
Authors: Olaisen Rho Henry , Flocke Susan , Love Thomas 
Published: April 2017

ObjectiveWe evaluate the effectiveness of a swim skill acquisition intervention among Latino youths, ages 3–14, a minority population at increased risk of drowning.MethodsParents were recruited through community institutions to have their children participate in group swim lessons. Each child's swim ability was assessed at baseline, and they were then exposed to swim lessons over an 8-week period, taught by trained professionals. The swim skill curriculum focused on water safety, flotation and endurance, at five levels of increasing skill acquisition. Final swim ability was assessed on the last day of the child's participation. Programme effectiveness was measured using direct pre–post comparisons with and without adjustment for key moderators (age and gender) and a mediator (number of practices). We also present a bias-adjusted estimate comparing low with high practice volume relying on a propensity score analysis.ResultsAmong the 149 participating children, average acquisition was 12.3 swim skills (95% CI 10.7 to 14.1). Skill acquisition varied by age category (3–5, 6–9 and 10–14 years) and by gender. We found a strong practice intensity effect, with skill acquisition accelerated for those participating in 10 or more swimming lessons. The propensity-adjusted estimate of the impact of 10 or more compared with 9 or fewer lessons was 8.2 skills (95% CI 4.8 to 11.8).ConclusionsAn 8-week swim intervention is effective at building skills in a community-based sample of Latino children, ages 3–14 years. The number of swimming lessons was a far stronger correlate of skill acquisition than were age or gender.