bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Functional Interchange between the IE1 and pp71 Proteins of Human Cytomegalovirus and ICP0 of Herpes Simplex Virus 1
Authors: Lu Yongxu , Everett Roger D. 
Published: January 2015

ABSTRACT
Human cytomegalovirus (HCMV) immediate early protein IE1 and the tegument protein pp71 are required for efficient infection. These proteins have some functional similarities with herpes simplex virus 1 (HSV-1) immediate early protein ICP0, which stimulates lytic HSV-1 infection and derepresses quiescent HSV-1 genomes. All three proteins counteract antiviral restriction mediated by one or more components of promyelocytic leukemia (PML) nuclear bodies, and IE1 and pp71, acting together, almost completely complement ICP0 null mutant HSV-1. Here, we investigated whether ICP0 might substitute for IE1 or pp71 during HCMV infection. Using human fibroblasts that express ICP0, IE1, or pp71 in an inducible manner, we found that ICP0 stimulated replication of both wild-type (wt) and pp71 mutant HCMV while IE1 increased wt HCMV plaque formation and completely complemented the IE1 mutant. Although ICP0 stimulated IE2 expression from IE1 mutant HCMV and increased the number of IE2-positive cells, it could not compensate for IE1 in full lytic replication. These results are consistent with previous evidence that both IE1 and IE2 are required for efficient HCMV gene expression, but they also imply that IE2 functionality is influenced specifically by IE1, either directly or indirectly, and that IE1 may include sequences that have HCMV-specific functions. We discovered a mutant form of IE1 (YL2) that fails to stimulate HCMV infection while retaining 30 to 80% of the activity of the wt protein in complementing ICP0 null mutant HSV-1. It is intriguing that the YL2 mutation is situated in the region of IE1 that is shared with IE2 and which is highly conserved among primate cytomegaloviruses.

IMPORTANCE
Herpesvirus gene expression can be repressed by cellular restriction factors, one group of which is associated with structures known as ND10 or PML nuclear bodies (PML NBs). Regulatory proteins of several herpesviruses interfere with PML NB-mediated repression, and in some cases their activities are transferrable between different viruses. For example, the requirement for ICP0 during herpes simplex virus 1 (HSV-1) infection can be largely replaced by ICP0-related proteins expressed by other alphaherpesviruses and even by a combination of the unrelated IE1 and pp71 proteins of human cytomegalovirus (HCMV). Here, we report that ICP0 stimulates gene expression and replication of wt HCMV but cannot replace the need for IE1 during infection by IE1-defective HCMV mutants. Therefore, IE1 includes HCMV-specific functions that cannot be replaced by ICP0.
Paediatric multiple sclerosis: a qualitative study of families’ diagnosis experiences
Authors: Hinton Denise , Kirk Susan 
Published: January 2015

ObjectiveTo examine children's and parents’ experiences of obtaining a diagnosis of paediatric multiple sclerosis (MS) and identify potential facilitators and barriers to early diagnosis.DesignQualitative, semi-structured interviews conducted face-to-face in home settings with 31 parents and 21 children and adolescents (8–17 years old) with a clinical diagnosis of MS. Participants were recruited from 16 NHS Trusts and four MS voluntary organisations in the UK. Interviews were recorded and transcribed verbatim and analysed using the constant comparative method.ResultsTime to diagnosis ranged from 1 to 96 months (median 11.5, mean 23.3, SD 27.3). The findings suggest that delayed presentation to healthcare services, generalists’ assumptions about the nature of reported symptoms, lack of awareness of paediatric MS and delayed referral to specialists in paediatric MS were barriers to early investigation and accurate diagnosis. Children, adolescents and parents felt that their concerns about the child's health were not always taken seriously during medical consultations and that clinicians could be reluctant to diagnose MS in childhood. This created additional uncertainty about the child's condition and long-term prognosis.ConclusionsObtaining a diagnosis of paediatric MS can be a challenging and lengthy process with potentially adverse implications for the health of children/adolescents. Valuing families’ knowledge and experience of their child's health, performing a thorough medical examination early in the disease course and organising prompt referrals may aid the early investigation and diagnosis of this disease. In view of the diagnostic challenges, children/adolescents with suspected MS would benefit from early referrals to specialists in paediatric MS.
Comparison of an automated rapid plasma reagin (RPR) test with the conventional RPR card test in syphilis testing
Authors: Lee Jong-Han , Lim Chae Seung , Lee Min-Geol , Kim Hyon-Suk 
Published: January 2015

ObjectiveWe compared the automated non-treponemal reagin (rapid plasma reagin (RPR)) test with the conventional RPR card test for usefulness in clinical applications.SettingA comparative study of laboratory methods using clinical specimens in a single institute.ParticipantsA total of 112 serum samples including 59Treponema pallidumparticle agglutination (TPPA)-positive and 53 TPPA-negative specimens were evaluated.Outcome measuresHiSens Auto RPR LTIA (HBI, Anyang, Korea) was compared with Macro-Vue RPR Card Tests (Becton Dickinson BD Microbiology Systems, Sparks, Maryland, USA). Treponemal-specific tests were performed by Serodia TPPA assay (Fujirebio, Tokyo, Japan). The percentage agreement, κ value and overall sensitivity and specificity of the two RPR tests were compared. Seroconversion rates after treatment were also compared for each RPR test.ResultsThe percentage agreement between the two RPR tests was 78.6% (κ 0.565; 95% CI 0.422 to 0.709). Sensitivity and specificity of the automated RPR test relative to the TPPA test was 52.5% (95% CI 39.1% to 65.7%) and 94.3% (95% CI 84.3% to 98.8%), respectively, while the same values for the conventional RPR card test were 86.4% (95% CI 75% to 93.9%) and 94.3% (95% CI 84.3% to 98.8%), respectively. The conventional RPR card test showed overall higher positivity than the automated RPR test, whereas the automated RPR test showed higher seroconversion (43.5%, 10/23) than the conventional RPR card test (4.3%, 1/23) in treated patients.ConclusionsThe automated RPR test showed overall lower sensitivity than the conventional RPR test based on the treponemal test, but higher seroconversion after treatment. The automated RPR test could be used to monitor treatment response, especially in the reverse screening algorithm in syphilis testing.
Trunk muscle exercises as a means of improving postural stability in people with Parkinson's disease: a protocol for a randomised controlled trial
Authors: Hubble Ryan P , Naughton Geraldine A , Silburn Peter A , Cole Michael H 
Published: January 2015

IntroductionExercise has been shown to improve clinical measures of strength, balance and mobility, and in some cases, has improved symptoms of tremor and rigidity in people with Parkinson's disease (PD). However, to date, no research has examined whether improvements in trunk control can remedy deficits in dynamic postural stability in this population. The proposed randomised controlled trial aims to establish whether a 12-week exercise programme aimed at improving dynamic postural stability in people with PD; (1) is more effective than education; (2) is more effective when training frequency is increased; and (3) provides greater long-term benefits than education.Methods/designForty-five community-dwelling individuals diagnosed with idiopathic PD with a falls history will be recruited. Participants will complete baseline assessments including tests of cognition, vision, disease severity, fear of falling, mobility and quality of life. Additionally, participants will complete a series of standing balance tasks to evaluate static postural stability, while dynamic postural control will be measured during walking using head and trunk-mounted three-dimensional accelerometers. Following baseline testing, participants will be randomly-assigned to one of three intervention groups, who will receive either exercise once per week, exercise 3 days/week, or education. Participants will repeat the same battery of tests conducted at baseline after the 12-week intervention and again following a further 12-week sustainability period.DiscussionThis study has the potential to show that low-intensity and progressive trunk exercises can provide a non-invasive and effective means for maintaining or improving postural stability for people with PD. Importantly, if the programme is noted to be effective, it could be easily performed by patients within their home environment or under the guidance of available allied health professionals.Trial registration numberThe protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613001175763).
The effect on quality of life of vitamin D administration for advanced cancer treatment (VIDAFACT study): protocol of a randomised controlled trial
Authors: Martinez-Alonso Montserrat , Dusso Adriana , Ariza Gemma , Nabal Maria 
Published: January 2015

IntroductionVitamin D is related to resistance to chronic diseases, physiological parameters and functional measures. All of these relationships underscore the potential benefits of cholecalciferol or D3 (nutritional vitamin D) in cancer. This is the first study designed to obtain conclusive evidence on the effect of cholecalciferol in advanced patients with cancer. The main goal is to assess its effects on the patient's perceived quality of life. Cholecalciferol's impact on fatigue and physical performance, as well as its cost utility, will also be assessed.Methods and analysisA randomised triple-blind phase II/III placebo-controlled multicentre trial has been designed. Patients satisfying the inclusion and exclusion criteria will be randomly assigned to receive cholecalciferol or placebo. Eligible patients will be adults with a locally advanced or metastatic or inoperable solid cancer in palliative care, who have given signed informed consent and have matched inclusion and exclusion criteria. The randomisation will be based on a computer-generated procedure and centralised by the pharmacy service of the coordinating centre. The assigned treatment will be administered by the hospital's pharmacy to conceal group allocation for patients and healthcare providers. Cholecalciferol (4000 IU/day) or placebo, starting at day 15 and continuing up to day 42, will be added to palliative care treatment. Outpatient visits will be scheduled every 14 days.Ethics and disseminationEthical approval was received from the Medical Ethical Commitee of the HUAV (CEIC-1169). Participants and their families will receive the research findings which will also be disseminated on local and national media, presented at national and international meetings of the specialty, and published in peer-reviewed scientific journals.Trial registration numberEudraCT: 2013-003478-29.
Representations of the health value of vitamin D supplementation in newspapers: media content analysis
Authors: Caulfield Timothy , Clark Marianne I , McCormack James P , Rachul Christen , Field Catherine J 
Published: January 2015

ObjectiveTo examine the nature of media coverage of vitamin D in relation to its role in health and the need for supplements.DesignMedia content analysis.SettingPrint articles from elite newspapers in the UK, the USA and Canada.Participants294 print newspaper articles appearing over 5 years (2009–2014).ResultsNewspaper coverage of vitamin D generally supported supplementation. The most common framing of vitamin D in print articles was “adequate vitamin D is necessary for good health.” Articles also framed vitamin D as difficult to obtain from food supply and framed vitamin D deficiency as a widespread concern. In discussions of supplementation, 80% articles suggested supplementation is or may be necessary for the general population, yet almost none of the articles discussed the potential harms of vitamin D supplementation in any detail.Print articles named 40 different health conditions in relationship to vitamin D. The most commonly cited conditions included bone health, cancer and cardiovascular health. Although print articles referred to a wide range of scholarly research on vitamin D with varying degrees of endorsement for supplementation, a general tone of support for vitamin D supplementation in media coverage persisted.ConclusionsNewspaper articles conveyed overall support for vitamin D supplementation. News articles linked vitamin D to a wide range of health conditions for which there is no conclusive scientific evidence. Media coverage downplayed the limitations of existing science and overlooked any potential risks associated with supplementation.
Neural biomarkers for assessing different types of imagery in pictorial health warning labels for cigarette packaging: a cross-sectional study
Authors: Newman-Norlund Roger D , Thrasher James F , Fridriksson Johann , Brixius William , Froeliger Brett , Hammond David , Cummings Michael K 
Published: January 2015

ObjectiveCountries around the world have increasingly adopted pictorial health warning labels (HWLs) for tobacco packages to warn consumers about smoking-related risks. Research on how pictorial HWLs work has primarily analysed self-reported responses to HWLs; studies at the neural level comparing the brain's response to different types of HWLs may provide an important complement to prior studies, especially if self-reported responses are systematically biased. In this study we characterise the brain's response to three types of pictorial HWLs for which prior self-report studies indicated different levels of efficacy.MethodsCurrent smokers rated pictorial HWLs and then observed the same HWLs during functional MRI (fMRI) scanning. Fifty 18–50-year-old current adult smokers who were free from neurological disorders were recruited from the general population and participated in the study. Demographics, smoking-related behaviours and self-reported ratings of pictorial HWL stimuli were obtained prior to scanning. Brain responses to HWLs were assessed using fMRI, focusing on a priori regions of interest.ResultsPictorial HWL stimuli elicited activation in a broad network of brain areas associated with visual processing and emotion. Participants who rated the stimuli as more emotionally arousing also showed greater neural responses at these sites.ConclusionsSelf-reported ratings of pictorial HWLs are correlated with neural responses in brain areas associated with visual and emotional processing. Study results cross-validate self-reported ratings of pictorial HWLs and provide insights into how pictorial HWLs are processed.
Health system reforms, violence against doctors and job satisfaction in the medical profession: a cross-sectional survey in Zhejiang Province, Eastern China
Authors: Wu Dan , Wang Yun , Lam Kwok Fai , Hesketh Therese 
Published: January 2015

ObjectiveTo explore the factors influencing doctors’ job satisfaction and morale in China, in the context of the ongoing health system reforms and the deteriorating doctor–patient relationship.DesignCross-sectional survey using self-completion questionnaires.Study settingThe survey was conducted from March to May 2012 among doctors at the provincial, county and primary care levels in Zhejiang Province, China.ResultsThe questionnaire was completed by 202 doctors. Factors which contributed most to low job satisfaction were low income and long working hours. Provincial level doctors were most dissatisfied while primary care doctors were the least dissatisfied. Three per cent of doctors at high-level hospitals and 27% of those in primary care were satisfied with the salary. Only 7% at high-level hospitals were satisfied with the work hours, compared to 43% in primary care. Less than 10% at high levels were satisfied with the amount of paid vacation time (3%) and paid sick leave (5%), compared with 38% and 41%, respectively, in primary care. Overall, 87% reported that patients were more likely to sue and that patient violence against doctors was increasing. Only 4.5% wanted their children to be doctors. Of those 125 who provided a reason, 34% said poor pay, 17% said it was a high-risk profession, and 9% expressed concerns about personal insecurity or patient violence.ConclusionsDoctors have low job satisfaction overall. Recruitment and retention of doctors have become major challenges for the Chinese health system. Measures must be taken to address this, in order to ensure recruitment and retention of doctors in the future. These measures must first include reduction of doctors’ workload, especially at provincial hospitals, partly through incentivisation of appropriate utilisation of primary care, increase in doctors’ salary and more effective measures to tackle patient violence against doctors.
A randomised controlled trial of aerobic exercise after transient ischaemic attack or minor stroke to prevent cognitive decline: the MoveIT study protocol
Authors: Boss H M , Van Schaik S M , Deijle I A , de Melker E C , van den Berg B T J , Scherder E J A , Bosboom W M J , Weinstein H C , Van den Berg-Vos R M 
Published: January 2015

IntroductionPatients with transient ischaemic attack (TIA) or stroke are at risk for cognitive impairment and dementia. Currently, there is no known effective strategy to prevent this cognitive decline. Increasing evidence exists that physical exercise is beneficial for cognitive function. However, in patients with TIA or stroke who are at risk of cognitive impairment and dementia, only a few trials have been conducted. In this study, we aim to investigate whether a physical exercise programme (MoveIT) can prevent cognitive decline in patients in the acute phase after a TIA or minor ischaemic stroke.Methods and analysisA single-blinded randomised controlled trial will be conducted to investigate the effect of an aerobic exercise programme on cognition compared with usual care. 120 adult patients with a TIA or minor ischaemic stroke less than 1 month ago will be randomly allocated to an exercise programme consisting of a 12-week aerobic exercise programme and regular follow-up visits to a specialised physiotherapist during the period of 1 year or to usual care. Outcome measures will be assessed at the baseline, and at the 1-year and 2-year follow-up. The primary outcome is cognitive functioning measured with the Montreal Cognitive Assessment (MoCA) test and with additional neuropsychological tests. Secondary outcomes include maximal exercise capacity, self-reported physical activity and measures of secondary prevention.Ethics and disseminationThe study received ethical approval from the VU University Amsterdam Ethics committee (2011/383). The results of this study will be published in peer-reviewed journals and presented at international conferences. We will also disseminate the main results to our participants in a letter.Trial registration numberThe Nederlands Trial Register NTR3884.
A randomised controlled non-inferiority trial of primary care-based facilitated access to an alcohol reduction website (EFAR Spain): the study protocol
Authors: López-Pelayo Hugo , Wallace Paul , Segura Lidia , Miquel Laia , Díaz Estela , Teixidó Lidia , Baena Begoña , Struzzo Pierliugio , Palacio-Vieira Jorge , Casajuana Cristina , Colom Joan , Gual Antoni 
Published: January 2015

IntroductionEarly identification (EI) and brief interventions (BIs) for risky drinkers are effective tools in primary care. Lack of time in daily practice has been identified as one of the main barriers to implementation of BI. There is growing evidence that facilitated access by primary healthcare professionals (PHCPs) to a web-based BI can be a time-saving alternative to standard face-to-face BIs, but there is as yet no evidence about the effectiveness of this approach relative to conventional BI. The main aim of this study is to test non-inferiority of facilitation to a web-based BI for risky drinkers delivered by PHCP against face-to-face BI.Method and analysisA randomised controlled non-inferiority trial comparing both interventions will be performed in primary care health centres in Catalonia, Spain. Unselected adult patients attending participating centres will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Participants with positive results will be requested online to complete a trial module including consent, baseline assessment and randomisation to either face-to-face BI by the practitioner or BI via the alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 3 months and 1 year using the full AUDIT and D5-EQD5 scale. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis.Ethics and disseminationThe protocol was approved by the Ethics Commmittee of IDIAP Jordi Gol i Gurina P14/028. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations.Trial registration numberClinicalTrials.govNCT02082990.
Prevalence and molecular characteristics of methicillin-resistantStaphylococcus aureusamong skin and soft tissue infections in an emergency department in Guyana
Authors: Dozois Adeline , Thomsen Isaac , Jimenez-Truque Natalia , Soper Nicole , Pearson Alexis , Mohamed-Rambaran Pheona , Dettorre Kristen B , Creech C Buddy , Wright Seth W 
Published: January 2015

ObjectiveThe characteristics of staphylococcal skin and soft tissue infections (SSTIs) are poorly understood in northern South America and the Caribbean. The objectives of this study were to determine the frequency of methicillin resistance amongStaphylococcus aureusisolates in an emergency department (ED) in Guyana and to identify specific molecular characteristics of these methicillin-resistantStaphylococcus aureus(MRSA) strains.MethodsThis was a cross-sectional study conducted at the main teaching hospital in Georgetown, Guyana. Eligible subjects included patients of all ages with SSTIs with obtainable purulent material. Purulent material was cultured, andS. aureusisolates were evaluated for antibiotic susceptibilities by disc diffusion. Molecular characterisation of MRSA isolates included identification of SCCmectype, assignment of genetic relatedness by rep-PCR and determination of the presence of two exotoxins, Panton-Valentine Leukocidin (PVL) and LukAB.ResultsEighty-five samples were collected; of these, 47 grewS. aureus.24 of the 47S. aureussamples were MRSA (51%; 95% CI 37% to 65%), representing 28% of all samples. All MRSA isolates were SCCmectype IV, PVL positive, LukAB positive and were highly related to the current epidemic clone in the USA, USA300.ConclusionsHere, we demonstrate a clinically significant proportion of methicillin resistance in SSTI-associated staphylococcal isolates. Guyanese isolates were highly related to the most common community-associated strain seen in the USA, USA300. These results have important implications for empiric antibiotic therapy and infection control policies in Guyana and similar settings.