bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in Pseudorabies Virus Glycoproteins gB, gD, and gH Functionally Compensate for the Absence of gL
Authors: Schröter Christina , Vallbracht Melina , Altenschmidt Jan , Kargoll Sabrina , Fuchs Walter , Klupp Barbara G. , Mettenleiter Thomas C. 
Published: December 2015

ABSTRACT

Entry of herpesviruses depends on the combined action of viral glycoprotein B (gB) and the heterodimeric gH/gL complex, which are activated by binding of the virion to specific cellular receptors. While gB carries signatures of a bona fide fusion protein, efficient membrane fusion requires gH/gL. However, although gB and gH/gL are essential for entry, the alphaherpesvirus pseudorabies virus (PrV) is capable of limited cell-to-cell spread in the absence of gL. To understand gH/gL function in more detail, the limited spread of PrV-ΔgL was used for reversion analyses by serial cell culture passages. In a first experiment, an infectious gL-negative mutant in which gL function was replaced by generation of a gD-gH hybrid protein was isolated (B. G. Klupp and T. C. Mettenleiter, J Virol 73:3014–3022, 1999). In a second, independent experiment PrV-ΔgLPassB4.1, which also replicated productively without gL, was isolated. Sequence analysis revealed mutations in gH but also in gB and gD. In a transfection-based fusion assay, two amino acid substitutions in the N-terminal part of gH
B4.1
(L
70
P and W
103
R) were found to be sufficient to compensate for lack of gL, while mutations present in gB
B4.1
enhanced fusogenicity. Coexpression of gB
B4.1
with the homologous gH
B4.1
resulted in strongly increased syncytium formation, which was further augmented by truncation of the gB
B4.1
C-terminal 29 amino acids. Nevertheless, gH was still required for membrane fusion. Surprisingly, coexpression of gD
B4.1
blocked syncytium formation in the fusion assays, which could be attributed to a V
106
A substitution within the ectodomain of gD
B4.1
.

IMPORTANCE
In contrast to many other enveloped viruses, herpesviruses rely on the concerted action of four viral glycoproteins for membrane fusion during infectious entry. Although the highly conserved gB shows signatures of a fusion protein, for fusion induction it requires the gH/gL complex, whose role is still elusive. Here we demonstrated fusion activation by gH in the absence of gL after reversion analysis of gL-deleted pseudorabies virus. This gL-independent fusion activity depended on single amino acid exchanges affecting the gL-binding domain in gH, increasing fusogenicity in gB and allowing negative fusion regulation by gD. Thus, our results provide novel information on the interplay in the fusion machinery of herpesviruses.
Price elasticity of tobacco products among economic classes in India, 2011–2012
Authors: Selvaraj Sakthivel , Srivastava Swati , Karan Anup 
Published: December 2015

ObjectivesThe objectives of this study are to: (1) examine the pattern of price elasticity of three major tobacco products (bidi, cigarette and leaf tobacco) by economic groups of population based on household monthly per capita consumption expenditure in India and (2) assess the effect of tax increases on tobacco consumption and revenue across expenditure groups.SettingData from the 2011–2012 nationally representative Consumer Expenditure Survey from 101 662 Indian households were used.ParticipantsHouseholds which consumed any tobacco or alcohol product were retained in final models.Primary outcome measuresThe study draws theoretical frameworks from a model using the augmented utility function of consumer behaviour, with a two-stage two-equation system of unit values and budget shares. Primary outcome measures were price elasticity of demand for different tobacco products for three hierarchical economic groups of population and change in tax revenue due to changes in tax structure. We finally estimated price elasticity of demand forbidi, cigarette and leaf tobacco and effects of changes in their tax rates on demand for these tobacco products and tax revenue.ResultsOwn price elasticities forbidiwere highest in the poorest group (−0.4328) and lowest in the richest group (−0.0815). Cigarette own price elasticities were −0.832 in the poorest group and −0.2645 in the richest group. Leaf tobacco elasticities were highest in the poorest (−0.557) and middle (−0.4537) groups.ConclusionsPoorer group elasticities were the highest, indicating that poorer consumers are more price responsive. Elasticity estimates show positive distributional effects of uniformbidiand cigarette taxation on the poorest consumers, as their consumption is affected the most due to increases in taxation. Leaf tobacco also displayed moderate elasticities in poor and middle tertiles, suggesting that tax increases may result in a trade-off between consumption decline and revenue generation. A broad spectrum rise in tax rates across all products is critical for tobacco control.
Internet-delivered cognitive-behavioural therapy for concerned significant others of people with problem gambling: study protocol for a randomised wait-list controlled trial
Authors: Magnusson Kristoffer , Nilsson Anders , Hellner Gumpert Clara , Andersson Gerhard , Carlbring Per 
Published: December 2015

IntroductionAbout 2.3% of the adult population in Sweden are considered to suffer from problem gambling, and it is estimated that only 5% of those seek treatment. Problem gambling can have devastating effects on the economy, health and relationship, both for the individual who gambles and their concerned significant other (CSO). No empirically supported treatment exists for the CSOs of people with problem gambling. Consequently, the aim of this study is to develop and evaluate a programme aimed at CSOs of treatment-refusing problem gamblers. The programme will be based on principles from cognitive behavioural therapy (CBT) and motivational interviewing. To benefit as many CSOs as possible, the programme will be delivered via the internet with therapist support via encrypted email and short weekly conversations via telephone.Methods and analysisThis will be a randomised wait-list controlled internet-delivered treatment trial. A CBT programme for the CSOs of people with problem gambling will be developed and evaluated. The participants will work through nine modules over 10 weeks in a secure online environment, and receive support via secure emails and over the telephone. A total of 150 CSOs over 18 years of age will be included. Measures will be taken at baseline and at 3, 6 and 12 months. Primary outcomes concern gambling-related harm. Secondary outcomes include the treatment entry of the individual who gambles, the CSO's levels of depression, anxiety, as well as relationship satisfaction and quality of life.Ethics and disseminationThe protocol has been approved by the regional ethics board of Stockholm, Sweden. This study will add to the body of knowledge on how to protect CSOs from gambling-related harm, and how to motivate treatment-refusing individuals to seek professional help for problem gambling.Trial registration numberNCT02250586.
Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review
Authors: Cooper Janine A , Cadogan Cathal A , Patterson Susan M , Kerse Ngaire , Bradley Marie C , Ryan Cristín , Hughes Carmel M 
Published: December 2015

ObjectiveTo summarise the findings of an updated Cochrane review of interventions aimed at improving the appropriate use of polypharmacy in older people.DesignCochrane systematic review. Multiple electronic databases were searched including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (from inception to November 2013). Hand searching of references was also performed. Randomised controlled trials (RCTs), controlled clinical trials, controlled before-and-after studies and interrupted time series analyses reporting on interventions targeting appropriate polypharmacy in older people in any healthcare setting were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation).SettingAll healthcare settings.ParticipantsOlder people (≥65 years) with ≥1 long-term condition who were receiving polypharmacy (≥4 regular medicines).Primary and secondary outcome measuresPrimary outcomes were the change in prevalence of appropriate polypharmacy and hospital admissions. Medication-related problems (eg, adverse drug reactions), medication adherence and quality of life were included as secondary outcomes.Results12 studies were included: 8 RCTs, 2 cluster RCTs and 2 controlled before-and-after studies. 1 study involved computerised decision support and 11 comprised pharmaceutical care approaches across various settings. Appropriateness was measured using validated tools, including the Medication Appropriateness Index, Beers’ criteria and Screening Tool of Older Person's Prescriptions (STOPP)/ Screening Tool to Alert doctors to Right Treatment (START). The interventions demonstrated a reduction in inappropriate prescribing. Evidence of effect on hospital admissions and medication-related problems was conflicting. No differences in health-related quality of life were reported.ConclusionsThe included interventions demonstrated improvements in appropriate polypharmacy based on reductions in inappropriate prescribing. However, it remains unclear if interventions resulted in clinically significant improvements (eg, in terms of hospital admissions). Future intervention studies would benefit from available guidance on intervention development, evaluation and reporting to facilitate replication in clinical practice.
COGNITIVE-HD study: protocol of an observational study of neurocognitive functioning and association with clinical outcomes in adults with end-stage kidney disease treated with haemodialysis
Authors: Palmer Suetonia C , Ruospo Marinella , Barulli Maria Rosaria , Iurillo Annalisa , Saglimbene Valeria , Natale Patrizia , Gargano Letizia , Murgo Angelo M , Loy Clement , van Zwieten Anita , Wong Germaine , Tortelli Rosanna , Craig Jonathan C , Johnson David W , Tonelli Marcello , Hegbrant Jörgen , Wollheim Charlotta , Logroscino Giancarlo , Strippoli G F M 
Published: December 2015

IntroductionThe prevalence of cognitive impairment may be increased in adults with end-stage kidney disease compared with the general population. However, the specific patterns of cognitive impairment and association of cognitive dysfunction with activities of daily living and clinical outcomes (including withdrawal from treatment) among haemodialysis patients remain incompletely understood. The COGNITIVE impairment in adults with end-stage kidney disease treated with HemoDialysis (COGNITIVE-HD) study aims to characterise the age-adjusted and education-adjusted patterns of cognitive impairment (using comprehensive testing for executive function, perceptual-motor function, language, learning and memory, and complex attention) in patients on haemodialysis and association with clinical outcomes.Methods and analysisA prospective, longitudinal, cohort study of 750 adults with end-stage kidney disease treated with long-term haemodialysis has been recruited within haemodialysis centres in Italy (July 2013 to April 2014). Testing for neurocognitive function was carried out by a trained psychologist at baseline to assess cognitive functioning. The primary study factor is cognitive impairment and secondary study factors will be specific domains of cognitive function. The primary outcome will be total mortality. Secondary outcomes will be cause-specific mortality, major cardiovascular events, fatal and non-fatal myocardial infarction and stroke, institutionalisation, and withdrawal from treatment at 12 months.Ethics and disseminationThis protocol was approved before study conduct by the following responsible ethics committees: Catania (approval reference 186/BE; 26/09/2013), Agrigento (protocol numbers 61–62; 28/6/2013), USL Roma C (CE 39217; 24/6/2013), USL Roma F (protocol number 0041708; 23/7/2013), USL Latina (protocol number 20090/A001/2011; 12/7/2013), Trapani (protocol number 3413; 16/7/2013) and Brindisi (protocol number 40259; 6/6/2013). All participants have provided written and informed consent and can withdraw from the study at any time. The findings of the study will be disseminated through peer-reviewed journals and national and international conference presentations and to the participants through communication within the dialysis network in which this study is conducted.
How do we deal with multiple goals for care within an individual patient trajectory? A document content analysis of health service research papers on goals for care
Authors: Berntsen G K R , Gammon D , Steinsbekk A , Salamonsen A , Foss N , Ruland C , Fønnebø V 
Published: December 2015

ObjectivesPatients with complex long-term needs experience multiple parallel care processes, which may have conflicting or competing goals, within their individual patient trajectory (iPT). The alignment of multiple goals is often implicit or non-existent, and has received little attention in the literature. Research questions: (1) What goals for care relevant for the iPT can be identified from the literature? (2) What goal typology can be proposed based on goal characteristics? (3) How can professionals negotiate a consistent set of goals for the iPT?DesignDocument content analysis of health service research papers, on the topic of ‘goals for care’.SettingWith the increasing prevalence of multimorbidity, guidance regarding the identification and alignment of goals for care across organisations and disciplines is urgently needed.Participants70 papers that describe ‘goals for care’, ‘health’ or ‘the good healthcare process’ relevant to a general iPT, identified in a step-wise structured search of MEDLINE, Web of Science and Google Scholar.ResultsWe developed a goal typology with four categories. Three categories are professionally defined: (1) Functional, (2) Biological/Disease and (3) Adaptive goals. The fourth category is the patient's personally defined goals. Professional and personal goals may conflict, in which case goal prioritisation by creation of a goal hierarchy can be useful. We argue that the patient has the moral and legal right to determine the goals at the top of such a goal hierarchy. Professionals can then translate personal goals into realistic professional goals such as standardised health outcomes linked to evidence-based guidelines. Thereby, when goals are aligned with one another, the iPT will be truly patient centred, while care follows professional guidelines.ConclusionsPersonal goals direct professional goals and define the success criteria of the iPT. However, making personal goals count requires brave and wide-sweeping attitudinal, organisational and regulatory transformation of care delivery.
Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial
Authors: Ried-Larsen Mathias , Christensen Robin , Hansen Katrine B , Johansen Mette Y , Pedersen Maria , Zacho Morten , Hansen Louise S , Kofoed Katja , Thomsen Katja , Jensen Mette S , Nielsen Rasmus O , MacDonald Chris , Langberg Henning , Vaag Allan A , Pedersen Bente K , Karstoft Kristian 
Published: December 2015

IntroductionCurrent pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications.Methods and analysisThe study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment.Ethics and disseminationThis study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1–2014–114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences.Trial registration numberNCT02417012.
Multimorbidity prevalence and pattern in Indonesian adults: an exploratory study using national survey data
Authors: Hussain Mohammad Akhtar , Huxley Rachel R , Al Mamun Abdullah 
Published: December 2015

ObjectivesTo estimate the prevalence and pattern of multimorbidity in the Indonesian adult population.DesignCross-sectional study.SettingCommunity-based survey. The sampling frame was based on households in 13 of the 27 Indonesian provinces, representing about 83% of the Indonesian population.Participants9438 Indonesian adults aged 40 years and above.Main outcome measuresPrevalence and pattern of multimorbidity by age, gender and socioeconomic status.ResultsThe mean number of morbidities in the sample was 1.27 (SE±0.01). The overall age and sex standardised prevalence of multimorbidity was 35.7% (34.8% to 36.7%), with women having significantly higher prevalence of multimorbidity than men (41.5% vs 29.5%; p<0.001). Of those with multimorbidity, 64.6% (62.8% to 66.3%) were aged less than 60 years. Prevalence of multimorbidity was positively associated with age (pfor trend<0.001) and affluence (pfor trend<0.001) and significantly greater in women at all ages compared with men. For each 5-year increment in age there was an approximate 20% greater risk of multimorbidity in both sexes (18% in women 95% CI 1.14 to 1.22 and 22% in men 95% CI 1.18 to 1.26). Increasing age, female gender, non-Javanese ethnicity, and high per-capital expenditure were all significantly associated with higher odds of multimorbidity. The combination of hypertension with cardiac diseases, hypercholesterolemia, arthritis, and uric acid/gout were the most commonly occurring disease pairs in both sexes.ConclusionsMore than one-third of the Indonesian adult population are living with multimorbidity with women and the more wealthy being particularly affected. Of especial concern was the high prevalence of multimorbidity among younger individuals. Hypertension was the most frequently occurring condition common to most individuals with multimorbidity.
Improving occupational injury surveillance by using a severity threshold: development of a new occupational health indicator
Authors: Sears Jeanne M , Bowman Stephen M , Rotert Mary , Blanar Laura , Hogg-Johnson Sheilah 
Published: December 2015

BackgroundHospital discharge data are used for occupational injury surveillance, but observed hospitalisation trends are affected by trends in healthcare practices and workers’ compensation coverage that may increasingly impair ascertainment of minor injuries relative to severe injuries. The objectives of this study were to (1) describe the development of a severe injury definition for surveillance purposes and (2) assess the impact of imposing a severity threshold on estimated occupational and non-occupational injury trends.MethodsThree independent methods were used to estimate injury severity for the severe injury definition. 10 population-based hospital discharge databases were used to estimate trends (1998–2009), including the National Hospital Discharge Survey (NHDS) and State Inpatient Databases (SID) from the Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. Negative binomial regression was used to model injury trends with and without severity restriction and to test trend divergence by severity.ResultsTrend estimates for occupational injuries were biased downwards in the absence of severity restriction, more so than for non-occupational injuries. Imposing a severity threshold resulted in a markedly different historical picture.ConclusionsSeverity restriction can be used as an injury surveillance methodology to increase the accuracy of trend estimates, which can then be used by occupational health researchers, practitioners and policy-makers to identify prevention opportunities and to support state and national investments in occupational injury prevention efforts. The newly adopted state-based occupational health indicator, ‘Work-Related Severe Traumatic Injury Hospitalizations’, incorporates a severity threshold that will reduce temporal ascertainment threats to accurate trend estimates.
Romidepsin and Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL
Authors: Rozati Sima , Cheng Phil F. , Widmer Daniel S. , Fujii Kazuyasu , Levesque Mitchell P. , Dummer Reinhard 
Published: December 2015

Abstract
Purpose: Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies that despite available therapies commonly relapse. The emergence of combination epigenetic therapies in other hematologic malignancies have made investigation of such combinations in CTCL a priority. Here, we explore the synergistic antiproliferative effects of romidepsin, an HDAC inhibitor, and azacitidine, a demethylating agent, combination in CTCL.
Experimental Design: The growth inhibition under combination treatment and single agent was explored by the MTT cell viability assay and the Annexin V/propidium iodide (PI) apoptosis assay in different CTCL cell lines and tumor cells derived from Sézary syndrome patients. Quantitative analysis of a dose–effect relationship of romidepsin and azacitidine was done by the CompuSyn software. Investigation of mechanism of action was performed by flow cytometry, immunoblotting, qRT-PCR arrays, and chromatin immunoprecipitation. Global CpG methylation sequencing was utilized to study genome methylation alteration under the treatment modalities.
Results: The combination of romidepsin and azacitidine exerts synergistic antiproliferative effects and induction of apoptosis involving activation of the caspase cascade in CTCL cell lines and tumor cells derived from Sézary syndrome patients. We identified genes that were selectively induced by the combination treatment, such as the tumor suppressor gene RhoB that is linked to enhanced histone acetylation at its promoter region in parallel with pronounced expression of p21. Global CpG methylation sequencing in a CTCL cell line and tumor cells demonstrated a subset of genes with a unique change in methylation profile in the combination treatment.
Conclusions: The synergistic antiproliferative effects of romidepsin and azacitidine combination treatment justify further exploration in clinical trials for advanced CTCL. Clin Cancer Res; 22(8); 2020–31. ©2015 AACR.