bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Analysis of the Role of Toxoplasma gondii Nucleoside Triphosphate Hydrolases I and II in Acute Mouse Virulence and Immune Suppression
Authors: Olias Philipp , Sibley L. David 
Published: April 2016

ABSTRACT

Bioluminescent reporter assays have been widely used to study the effect of
Toxoplasma gondii
on host gene expression. In the present study, we extend these studies by engineering novel reporter cell lines containing a gamma-activated sequence (GAS) element driving firefly luciferase (FLUC). In RAW264.7 macrophages,
T. gondii
type I strain (GT1) infection blocked interferon gamma (IFN-γ)-induced FLUC activity to a significantly greater extent than infection by type II (ME49) and type III (CTG) strains. Quantitative trait locus (QTL) analysis of progeny from a prior genetic cross identified a genomic region on chromosome XII that correlated with the observed strain-dependent phenotype. This QTL region contains two isoforms of the
T. gondii
enzyme nucleoside triphosphate hydrolase (NTPase) that were the prime candidates for mediating the observed strain-specific effect. Using reverse genetic analysis we show that deletion of NTPase I from a type I strain (RH) background restored the higher luciferase levels seen in the type II (ME49) strain. Rather than an effect on IFN-γ-dependent transcription, our data suggest that NTPase I was responsible for the strain-dependent difference in FLUC activity due to hydrolysis of ATP. We further show that NTPases I and II were not essential for tachyzoite growth
in vitro
or virulence in mice. Our study reveals that although
T. gondii
NTPases are not essential for immune evasion, they can affect ATP-dependent reporters. Importantly, this limitation was overcome using an ATP-independent
Gaussia
luciferase, which provides a more appropriate reporter for use with
T. gondii
infection studies.
The prevalence of congenital heart defects in infants with cholestatic disorders of infancy: a single-centre study
Authors: Fattouh Aya M , Mogahed Engy A , Abdel Hamid Nehal , Sobhy Rodina , Saber Noha , El-Karaksy Hanaa 
Published: April 2016

BackgroundThere is deficiency of data about congenital heart defects (CHDs) in cholestatic disorders of infancy other than Alagille syndrome (AGS). We aimed to define the prevalence and types of CHDs in infants with various causes of cholestatic disorders of infancy.MethodsThis cross-sectional study was conducted on 139 infants presenting with cholestasis whether surgical or non-surgical. The study was carried out at the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. Full examination and investigations were done in an attempt to reach an aetiologic diagnosis for cholestasis, in addition to a comprehensive echocardiographic study.ResultsThe age at the onset of cholestasis ranged from 1 day to 7 months. Males constituted 61.2%. Biliary atresia (BA) was diagnosed in 39 patients (28%), AGS in 16 patients (11.5%), 27 patients had miscellaneous diagnoses and 57 cases had indeterminate aetiology. CHDs were detected in 55 patients (39.5%). Shunt lesions were detected in 24 patients (43.6%), pulmonary stenosis in 18 patients (32.7%) and combined lesions in 9 patients (16.4%). Three patients (5.5%) had abnormal cardiac situs. Only seven patients had clinical presentation suggestive of CHD. CHDs were detected in 14 patients with BA (35.9%), 15 patients with AGS (93.7%) and 26 patients in the remaining group (30.9%).ConclusionCHDs are not uncommon among cholestatic infants and are mostly asymptomatic. Echocardiographic examination of cholestatic infants is recommended particularly for patients with BA before undergoing hepatic portoenterostomy as presence of CHD may impact the anaesthetic planning and affect the outcome of hepatobiliary surgery.
MRI findings and return to play in football: a prospective analysis of 255 hamstring injuries in the UEFA Elite Club Injury Study
Authors: Ekstrand Jan , Lee Justin C , Healy Jeremiah C 
Published: April 2016

AimThe present study evaluated whether the MRI parameters of hamstring injuries in male professional football players correlate with time to return to play (RTP).Methods46 elite European football teams were followed prospectively for hamstring injuries between 2007 and 2014. Club medical staff recorded individual player exposure and time-loss after hamstring injury. MRI parameters were evaluated by two independent radiologists and correlated with the RTP data.ResultsA total of 255 grade 1 and 2 injuries were evaluated in this study. RTP was longer for grade 2 than grade 1 injuries (24±13, 95% CI 21 to 26 days vs 18±15, 95% CI 16 to 20 days; mean difference: 6, 95% CI 2 to 9 days, p=0.004, d=0.39). 84% of injuries affected the biceps femoris (BF) muscle, whereas 12% and 4% affected the semimembranosus (SM) and semitendinosus (ST), respectively. No difference in lay-off time was found for injuries to the three different muscles (BF 20±15 days, SM 18±11 days, ST 23±14 days; p=0.83). The recurrence rate was higher for BF injuries than for SM and ST injuries combined (18% vs 2%, p=0.009). The size of the oedema weakly correlated with time to RTP (r2=6–12%). No correlation was found between location of injury and time to RTP. The majority of the intramuscular injuries affected the MT junction (56% in grade 1 and 2 injuries), but no difference in lay-off time was found between the different types of injuries.ConclusionsThe radiological grade and size of the oedema correlate with time to RTP for both, grade 1 and 2 injuries. No correlations were found between time to RTP and the location and type of injury.
Does current provision of undergraduate education prepare UK medical students in ENT? A systematic literature review
Authors: Ferguson Gary R , Bacila Irina A , Swamy Meenakshi 
Published: April 2016

ObjectiveTo systematically identify and analyse all published literature relating to the provision of undergraduate education for preparedness in ear, nose and throat (ENT) surgery, as perceived by medical students and clinicians in the UK.DesignSystematic literature review.Data sources5 major databases were searched: MEDLINE, EMBASE, ERIC, Cochrane and Web of Science. The literature search was conducted from February to April 2015.Eligibility criteria for selecting studiesPrimary research or studies that report on the provision of undergraduate education for preparedness in ENT, from the perspective of medical students and clinicians in the UK. The timescale of searches was limited from 1999 onwards (ie, the past 15 years).Data extractionThe literature search was conducted by 2 independent reviewers. Search terms used involved the combination and variation of 5 key concepts, namely: medical student, clinician, ENT, undergraduate medical education and UK. A data extraction form was designed for and used in this study, based on guidelines provided by the UK National Health Service (NHS) Centre for Reviews and Dissemination. Textual narrative synthesis was used for data analysis.ResultsA total of 7 studies were included in the final review. 4 main themes were identified: confidence in managing patients, teaching delivery, student assessment and duration of rotations. A consistent finding in this review was that the majority of final year medical students and junior doctors did not feel adequately prepared to practise ENT. Important factors influencing preparedness in ENT included the duration of clinical rotations, the opportunity for hands-on learning and formal assessment.ConclusionsThe findings of this review suggest the need for further development of the ENT undergraduate curricula across the UK. However, there is insufficient evidence from which to draw strong conclusions; this in itself is beneficial as it highlights a gap in the existing literature and supports the need for primary research.
Proposals for enhanced health risk assessment and stratification in an integrated care scenario
Authors: Dueñas-Espín Ivan , Vela Emili , Pauws Steffen , Bescos Cristina , Cano Isaac , Cleries Montserrat , Contel Joan Carles , de Manuel Keenoy Esteban , Garcia-Aymerich Judith , Gomez-Cabrero David , Kaye Rachelle , Lahr Maarten M H , Lluch-Ariet Magí , Moharra Montserrat , Monterde David , Mora Joana , Nalin Marco , Pavlickova Andrea , Piera Jordi , Ponce Sara , Santaeugenia Sebastià , Schonenberg Helen , Störk Stefan , Tegner Jesper , Velickovski Filip , Westerteicher Christoph , Roca Josep 
Published: April 2016

ObjectivesPopulation-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario.SettingsThe five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL).ParticipantsResponsible teams for regional data management in the five ACT regions.Primary and secondary outcome measuresWe characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction.ResultsThere was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment.ConclusionsThe results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches. Applicability and impact of the proposals for enhanced clinical risk assessment require prospective evaluation.
Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study
Authors: Haslett Kate , Franks Kevin , Hanna Gerard G , Harden Susan , Hatton Matthew , Harrow Stephen , McDonald Fiona , Ashcroft Linda , Falk Sally , Groom Nicki , Harris Catherine , McCloskey Paula , Whitehurst Philip , Bayman Neil , Faivre-Finn Corinne 
Published: April 2016

IntroductionThe majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.Methods and analysisIsotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.Ethics and disseminationThe study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.Trial registration numberNCT01836692; Pre-results.
Effectiveness of multidisciplinary team case management: difference-in-differences analysis
Authors: Stokes Jonathan , Kristensen Søren Rud , Checkland Kath , Bower Peter 
Published: April 2016

ObjectivesTo evaluate a multidisciplinary team (MDT) case management intervention, at the individual (direct effects of intervention) and practice levels (potential spillover effects).DesignDifference-in-differences design with multiple intervention start dates, analysing hospital admissions data. In secondary analyses, we stratified individual-level results by risk score.SettingSingle clinical commissioning group (CCG) in the UK's National Health Service (NHS).ParticipantsAt the individual level, we matched 2049 intervention patients using propensity scoring one-to-one with control patients. At the practice level, 30 practices were compared using a natural experiment through staged implementation.InterventionPractice Integrated Care Teams (PICTs), using MDT case management of high-risk patients together with a summary record of care versus usual care.Direct and indirect outcome measuresPrimary measures of intervention effects were accident and emergency (A&E) visits; inpatient non-elective stays, 30-day re-admissions; inpatient elective stays; outpatient visits; and admissions for ambulatory care sensitive conditions. Secondary measures included inpatient length of stay; total cost of secondary care services; and patient satisfaction (at the practice level only).ResultsAt the individual level, we found slight, clinically trivial increases in inpatient non-elective admissions (+0.01 admissions per patient per month; 95% CI 0.00 to 0.01. Effect size (ES): 0.02) and 30-day re-admissions (+0.00; 0.00 to 0.01. ES: 0.03). We found no indication that highest risk patients benefitted more from the intervention. At the practice level, we found a small decrease in inpatient non-elective admissions (−0.63 admissions per 1000 patients per month; −1.17 to −0.09. ES: −0.24). However, this result did not withstand a robustness check; the estimate may have absorbed some differences in underlying practice trends.ConclusionsThe intervention does not meet its primary aim, and the clinical significance and cost-effectiveness of these small practice-level effects is debatable. There is an ongoing need to develop effective ways to reduce unnecessary attendances in secondary care for the high-risk population.
Assessment of the quantity of microorganisms associated with bronchiectasis in saliva, sputum and nasal lavage after periodontal treatment: a study protocol of a randomised controlled trial
Authors: Pinto Erika Horácio , Longo Priscila Larcher , Camargo Caroline Cristina Batista de , Dal Corso Simone , Lanza Fernanda De Cordoba , Stelmach Rafael , Athanazio Rodrigo , Fernandes Kristianne Porta Santos , Mayer Marcia Pinto Alves , Bussadori Sandra Kalil , Mesquita Ferrari Raquel Agnelli , Horliana Anna Carolina Ratto Tempestini 
Published: April 2016

IntroductionThe association between periodontal disease (PD) and chronic obstructive pulmonary disease (COPD) has been widely studied, with aspiration of periodontal pathogens being one of the most accepted causal mechanisms for pulmonary exacerbation. Periodontal treatment (PT) was associated with a decrease in these exacerbations. Bronchiectasis is a pulmonary disease that has many similarities to COPD; however, there are no studies correlating this condition to PD thus far. This study will evaluate if PT reduces proinflammatory cytokines in serum and saliva, as well as halitosis and the amount of microorganisms associated with exacerbation of bronchiectasis in saliva, sputum and nasal lavage 3 months after PT.Methods and analysisA total of 182 patients with PD and bronchiectasis will be randomly allocated to group 1 (positive control; scaling and root planing (SRP)+oral hygiene (OH)) or group 2 (experimental; SRP+photodynamic therapy+OH). After 3 months, samples of saliva, nasal lavage and sputum will be collected to determine the level ofPseudomonas aeruginosa,Staphylococcus aureusandPorphyromonas gingivalisby quantitative PCR. This protocol will determine the efficacy of PT in reducing the most likely niches of bronchiectasis exacerbation by comparing pre- and post-treatment microbiology samples. Furthermore, there will be assessment of oral halitosis and verification of inflammatory cytokines in serum and saliva.Ethics and disseminationThis protocol has been approved by the Research Ethics Committee of Universidade Nove de Julho. Data will be published in a peer-reviewed journal.Trial registration numberNCT02514226.
Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation
Authors: Sanghera Sabina , Barton Pelham , Bhattacharya Siladitya , Horne Andrew W , Roberts Tracy Elizabeth 
Published: April 2016

ObjectiveConduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and ‘no treatment’ to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation.MethodsWe developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported.ResultsOn average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required.ConclusionsThere is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.
Pain mechanisms and ultrasonic inflammatory activity as prognostic factors in patients with psoriatic arthritis: protocol for a prospective, exploratory cohort study
Authors: Højgaard Pil , Christensen Robin , Dreyer Lene , Mease Philip , Wit Maarten de , Skov Lone , Glintborg Bente , Christensen Anton Wulf , Ballegaard Christine , Bliddal Henning , Bukhave Kristine , Bartels Else Marie , Amris Kirstine , Ellegaard Karen , Kristensen Lars Erik 
Published: April 2016

IntroductionPersistent pain is a major concern for patients with psoriatic arthritis (PsA). Pain may be due to inflammatory activity or augmented central pain processing. Unawareness of the origin and mechanisms of pain can lead to misinterpretation of disease activity (by composite scores) and erroneous treatments. Ultrasonography (US) is a highly sensitive method to detect tissue inflammation. Evaluating pain mechanisms in relation to US measures may prove valuable in predicting response to treatment in PsA.AimsTo study the association and prognostic value of pain mechanisms, ultrasonic activity and clinical outcomes in patients with PsA who intensify antirheumatic treatment.Methods and analyses100 participants >18 years of age with PsA who initiate or switch antirheumatic treatment (biologicals and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs)) will be prospectively recruited from outpatient clinics in Copenhagen. All data (demographics, clinical, imaging, blood samples and patient-reported outcomes) will be collected at baseline and after 4 months. Pain is assessed by the PainDETECT Questionnaire, Visual Analogue Scale for pain, Swollen to Tender Joint Count Ratio, Widespread Pain Index and tender point examination. The association between pain variables and clinical/US characteristics will be described by correlation analyses. The predictive value of pain measures and baseline US scores on treatment response will be analysed with regression models. Outcomes are composite and clinical, as well as patient reported.Ethics and disseminationThe study is approved by the ethics committee of the Capital Region of Denmark (H-15009080) and has been designed in cooperation with patient research partners. The study is registered at clinicaltrials.gov (numberNCT02572700). Results will be disseminated through publication in international peer-reviewed journals.Trial registration numberNCT02572700, Pre-results.
Effectiveness of a nurse educational oral feeding programme on feeding outcomes in neonates: protocol for an interrupted time series design
Authors: Touzet Sandrine , Beissel Anne , Denis Angélique , Pillet Fabienne , Gauthier-Moulinier Hélène , Hommey Sophie , Claris Olivier 
Published: April 2016

IntroductionOral feeding is a complex physiological process. Several scales have been developed to assess the ability of the neonate to begin suck feedings and assist caregivers in determining feeding advancement. However, feeding premature neonates remains an ongoing challenge and depends above all on caregivers' feeding expertise. We will evaluate the effect of a nurse training programme on the achievement of full oral feeding with premature neonates.Methods and analysisThe study design will be an interrupted time series design with 3 phases: (1) A 6-month baseline period; (2) a 22-month intervention period and (3) a 6-month postintervention period. The intervention will consist of an educational programme, for nurses and assistant nurses, on feeding patterns in neonates. The training modules will be composed of a 2-day conference, 2 interactive multidisciplinary workshops, and routine practice nurse coaching. A total of 120 nurses and 12 assistant nurses, who work at the neonatal unit during the study period, will participate in the study. All premature neonates of <34 weeks postmenstrual age (PMA) will be included. The primary outcome will be the age of tube withdrawal PMA and chronological age are taken into account. The secondary outcomes will be the transition time, length of hospital stay, competent suckle feeding without cardiorespiratory compromise, rate of neonates presenting with feeding issues or feeding rejection signs, and current neonatal pathologies or deaths during hospital stay. A segmented regression analysis will be performed to assess the impact of the programme.Ethics and disseminationApproval for the study was obtained from the Hospital Ethics Committee, and the Institutional Review Board, as well as the French Data Protection Agency. The findings from the study will be disseminated through peer-reviewed journals, national and international conference presentations and public events.Trial registration numberNCT02404272 (https://clinicaltrials.gov).