bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Mutagenesis of Pseudorabies Virus and Epstein-Barr Virus gH Identifies a Structural Determinant within Domain III of gH Required for Surface Expression and Entry Function
Authors: Möhl Britta S. , Schröter Christina , Klupp Barbara G. , Fuchs Walter , Mettenleiter Thomas C. , Jardetzky Theodore S. , Longnecker Richard 
Published: December 2015

ABSTRACT
Herpesviruses infect cells using the conserved core fusion machinery composed of glycoprotein B (gB) and gH/gL. The gH/gL complex plays an essential but still poorly characterized role in membrane fusion and cell tropism. Our previous studies demonstrated that the conserved disulfide bond (DB) C278/C335 in domain II (D-II) of Epstein-Barr virus (EBV) gH has an epithelial cell-specific function, whereas the interface of D-II/D-III is involved in formation of the B cell entry complex by binding to gp42. To extend these studies, we compared gH of the alphaherpesvirus pseudorabies virus (PrV) with gH of the gammaherpesvirus EBV to identify functionally equivalent regions critical for gH function during entry. We identified several conserved amino acids surrounding the conserved DB that connects three central helices of D-III of PrV and EBV gH. The present study verified that the conserved DB and several contacting amino acids in D-III modulate cell surface expression and thereby contribute to gH function. In line with this finding, we found that DB C404/C439 and T401 are important for cell-to-cell spread and efficient entry of PrV. This parallel comparison between PrV and EBV gH function brings new insights into how gH structure impacts fusion function during herpesvirus entry.

IMPORTANCE
The alphaherpesvirus PrV is known for its neuroinvasion, whereas the gammaherpesvirus EBV is associated with cancer of epithelial and B cell origin. Despite low amino acid conservation, PrV gH and EBV gH show strikingly similar structures. Interestingly, both PrV gH and EBV gH contain a structural motif composed of a DB and supporting amino acids which is highly conserved within the
Herpesviridae
. Our study verified that PrV gH uses a minimal motif with the DB as the core, whereas the DB of EBV gH forms extensive connections through hydrogen bonds to surrounding amino acids, ensuring the cell surface expression of gH/gL. Our study verifies that the comparative analysis of distantly related herpesviruses, such as PrV and EBV, allows the identification of common gH functions. In addition, we provide an understanding of how functional domains can evolve over time, resulting in subtle differences in domain structure and function.
Use and safety of azithromycin in neonates: a systematic review
Authors: Smith Coral , Egunsola Oluwaseun , Choonara Imti , Kotecha Sailesh , Jacqz-Aigrain Evelyne , Sammons Helen 
Published: December 2015

ObjectivesTo identify the use and adverse drug reactions associated with azithromycin in neonates.SettingDatabases MEDLINE (1948–August 2015), EMBASE (1980–August 2015) and Pubmed (August 2015) were searched for studies on azithromycin in neonates.ParticipantsAll studies involving neonates (<28 days old) who have received at least a single dose of azithromycin for which safety was evaluated.Primary and secondary outcome measuresThe primary outcome was adverse event (AE) associated with use of azithromycin. Use of azithromycin in neonates was the secondary outcome.ResultsA total of 11 articles involving 473 neonates were identified. 371 AEs were reported. Adverse events were mainly respiratory (358/1000 neonate), neurological (273/1000 neonates) and gastrointestinal (196/1000 neonates) in origin. Azithromycin significantly reduced the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates (RR=0.83, 95% CI 0.71 to 0.98, p=0.02). There was no significant difference in the incidence of elevated liver enzymes between the azithromycin and placebo group (p=0.76). There were four cases of infantile hypertrophic pyloric stenosis (IHPS).ConclusionsAzithromycin significantly reduces the risk of BPD in preterm neonates. The relationship between azithromycin and IHPS requires further investigation.
Health conditions in a cohort of New Zealand Vietnam veterans: hospital admissions between 1988 and 2009
Authors: Cox Brian , McBride David , Broughton John , Tong Darryl 
Published: December 2015

ObjectivesTo inform the provision of support to veterans by analysing hospital discharge data, thereby identifying which conditions show an excess risk, require specific management strategies and deserve further investigation.SettingTertiary level care, including all public and private New Zealand hospitals.ParticipantsAll New Zealand Vietnam veterans with service between 1964 and 1972.Primary outcome measuresStandardised hospitalisation ratios (SHRs) were calculated based on the number of first observed hospital admissions for a condition, those expected being based on New Zealand national hospitalisation rates.ResultsThe SHR for all causes of hospitalisation was 1.18, 95% CI 1.15 to 1.21, with modest increases for the major common causes, cardio and cerebrovascular disease. Admission rates for chronic renal failure and chronic obstructive pulmonary disease were highest in the 2006–2009 time period. The highest statistically significant hospitalisation risk was for alcohol-related mental disorder, SHR 1.91, 99% CI 1.39 to 2.43.ConclusionsChronic renal failure has limited attribution to veteran service but along with chronic obstructive pulmonary disease has the potential to have high costs both to the individual and the health system. We suggest that routine surveillance of veterans by way of a ‘flag’ in national and primary care databases would facilitate the recognition of service-related conditions and the appropriate provision of healthcare.
Evaluating quality and its determinants in lipid control for secondary prevention of heart disease and stroke in primary care: a study in an inner London Borough
Authors: Dodhia Hiten , Kun Liu , Logan Ellis Hugh , Crompton James , Wierzbicki Anthony S , Williams Helen , Hodgkinson Anna , Balazs John 
Published: December 2015

ObjectivesTo assess quality of management and determinants in lipid control for secondary prevention of cardiovascular disease (CVD) using multilevel regression models.DesignCross-sectional study.SettingInner London borough, with a primary care registered population of 378 000 (2013).Participants48/49 participating general practices with 7869 patients on heart disease/stroke registers were included.Outcome measures(1) Recording of current total cholesterol levels and lipid control according to national evidence-based standards. (2) Assessment of quality by age, sex, ethnicity, deprivation, presence of other risks or comorbidity in meeting both lipid measurement and control standards.ResultsSome process standards were not met. Patients with a current cholesterol measurement >5 mmol/L were less likely to have a current statin prescription (adjusted OR=3.10; 95% CI 2.70 to 3.56). They were more likely to have clustering of other CVD risk factors. Women were significantly more likely to have raised cholesterol after adjustment for other factors (adjusted OR=1.74; 95% CI 1.53 to 1.98).ConclusionsIn this study, the key factor that explained poor lipid control in people with CVD was having no current prescription record of a statin. Women were more likely to have poorly controlled cholesterol (independent of comorbid risk factors and after adjusting for age, ethnicity, deprivation index and practice-level variation). Women with CVD should be offered statin prescription and may require higher statin dosage for improved control.
The abdominal drawing-in manoeuvre for detecting activity in the deep abdominal muscles: is this clinical tool reliable and valid?
Authors: Kaping Karsten , Äng Björn O , Rasmussen-Barr Eva 
Published: December 2015

ObjectiveThe abdominal drawing-in manoeuvre (ADIM) is a common clinical tool for manually assessing whether a preferential activation of the deep abdominal muscles in patients with low back pain (LBP) is ‘correct’ or not. The validity and reliability of manual assessment of the ADIM are, however, as yet unknown. This study evaluated the concurrent and discriminative validity and reliability of the manually assessed ADIM.DesignSingle-blinded cross-sectional study.SettingsGeneral population in Stockholm County, Sweden.ParticipantsThe study sample comprised 38 participants seeking care for LBP, and 15 healthy subjects.MeasuresThe manual ADIM was assessed as correct or not following a standard procedure. Ultrasound imaging (USI) was used as the concurrent reference (gold standard) for the manually assessed ADIM by calculating a ratio of the change in muscle thickness between the resting and the contracted states: the correlation between manual test and USI was calculated. Discriminative validity was analysed by calculating sensitivity and specificity. A sample of 24 participants was analysed with κ coefficients for interobserver reliability between two raters.ResultsThe concurrent validity between the manual ADIM and the ADIM–USI ratios showed poor correlations (r=0.13–0.40). The discriminative validity of the manually assessed ADIM to predict LBP showed a sensitivity/specificity of 0.30/0.73, while the ADIM–USI ratio to predict LBP showed 0.19/0.87. The interobserver reliability for the manually assessed ADIM revealed substantial agreement: K=0.71, CI (95%) 0.41 to 1.00.ConclusionsAlthough the interobserver reliability of the manually assessed ADIM was high, the concurrent and discriminative validity were both low for examining the preferential activity of the deep abdominal muscles. Neither the manually assessed ADIM nor the ultrasound testing discriminated between participants with LBP and healthy subjects regarding preferential activity of the transversus muscle as this ability/inability was also present in healthy subjects.
High prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia: a nationwide survey
Authors: Sugai Takuro , Suzuki Yutaro , Yamazaki Manabu , Shimoda Kazutaka , Mori Takao , Ozeki Yuji , Matsuda Hiroshi , Sugawara Norio , Yasui-Furukori Norio , Minami Yoshitake , Okamoto Kurefu , Sagae Toyoaki , Someya Toshiyuki 
Published: December 2015

ObjectivesTo clarify the prevalence of underweight and overweight/obesity, and laboratory data for nutritional status in Japanese outpatients and inpatients with schizophrenia.DesignCross-sectional study.SettingA questionnaire conducted in inpatient and outpatient facilities in Japan.ParticipantsThe population of adult patients with schizophrenia in Japan (N=23 116).Main outcome measuresThe prevalence of underweight and undernutrition in Japanese inpatients and outpatients with schizophrenia.ResultsWe conducted a large-scale investigation of the prevalence of underweight and undernutrition in 520 outpatient facilities and 247 inpatient facilities belonging to the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7655 outpatients and 15 461 inpatients with schizophrenia. There was a significant difference in the distribution of three body mass index levels between outpatients and inpatients (p<0.001). The proportion of underweight inpatients with schizophrenia was significantly higher than that among outpatients (p<0.001). Age-specific analysis revealed that the proportion of underweight individuals aged ≥40 years was higher in inpatients than in outpatients and in the general Japanese population. The proportion of individuals with hypocholesterolaemia was significantly higher in inpatients with schizophrenia than in outpatients (p<0.001). There was a significant difference in the severity of underweight between outpatients and inpatients with schizophrenia; the proportion of severe underweight in inpatients was twofold higher than in outpatients.ConclusionsThe prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia was higher than in outpatients and the general population. Therefore, the physical risk of inpatients should be carefully considered in clinical practice.
Cost-effectiveness of a European ST-segment elevation myocardial infarction network: results from the CatalanCodi Infartnetwork
Authors: Regueiro Ander , Bosch Julia , Martín-Yuste Victoria , Rosas Alba , Faixedas Maria Teresa , Gómez-Hospital Joan Antoni , Figueras Jaume , Curós Antoni , Cequier Angel , Goicolea Javier , Fernández-Ortiz Antonio , Macaya Carlos , Tresserras Ricard , Pellisé Laura , Sabaté Manel 
Published: December 2015

ObjectivesTo evaluate the cost-effectiveness of the ST-segment elevation myocardial infarction (STEMI) network of Catalonia (Codi Infart).DesignCost-utility analysis.SettingThe analysis was from the Catalonian Autonomous Community in Spain, with a population of about 7.5 million people.ParticipantsPatients with STEMI treated within the autonomous community of Catalonia (Spain) included in the IAM CAT II-IV andCodi Infartregistries.Outcome measuresCosts included hospitalisation, procedures and additional personnel and were obtained according to the reperfusion strategy. Clinical outcomes were defined as 30-day avoided mortality and quality-adjusted life-years (QALYs), before (N=356) and after network implementation (N=2140).ResultsA substitution effect and a technology effect were observed; aggregate costs increased by 2.6%. The substitution effect resulted from increased use of primary coronary angioplasty, a relatively expensive procedure and a decrease in fibrinolysis. Primary coronary angioplasty increased from 31% to 89% with the network, and fibrinolysis decreased from 37% to 3%. Rescue coronary angioplasty declined from 11% to 4%, and no reperfusion from 21% to 4%. The technological effect was related to improvements in the percutaneous coronary intervention procedure that increased efficiency, reducing the average length of the hospital stay. Mean costs per patient decreased from €8306 to €7874 for patients with primary coronary angioplasty. Clinical outcomes in patients treated with primary coronary angioplasty did not change significantly, although 30-day mortality decreased from 7.5% to 5.6%. The incremental cost-effectiveness ratio resulted in an extra cost of €4355 per life saved (30-day mortality) and €495 per QALY. Below a cost threshold of €30 000, results were sensitive to variations in costs and outcomes.ConclusionsThe Catalan STEMI network (Codi Infart) is cost-efficient. Further studies are needed in geopolitical different scenarios.
Primary Care Atrial Fibrillation Service: outcomes from consultant-led anticoagulation assessment clinics in the primary care setting in the UK
Authors: Das Moloy , Panter Lee , Wynn Gareth J , Taylor Rob M , Connor Neil , Mills Joseph D , Kirchhof Paulus , Gupta Dhiraj 
Published: December 2015

ObjectiveStroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients with AF are not anticoagulated, with severe consequences for stroke prevention. We aimed to determine the outcome of an innovative Primary Care AF (PCAF) service on anticoagulation uptake in a cohort of high-risk patients with AF in the UK.MethodsThe PCAF service is a novel cooperative pathway providing specialist resources within general practitioner (GP) practices. It utilises a four-phase protocol to identify high-risk patients with AF (CHA2DS2-VASc ≥1) who are suboptimally anticoagulated, and delivers Consultant-led anticoagulation assessment within the local GP practice. We assessed rates of anticoagulation in high-risk patients before and after PCAF service intervention, and determined compliance with newly-initiated anticoagulation at follow-up.ResultsThe PCAF service was delivered in 56 GP practices (population 386 624; AF prevalence 2.1%) between June 2012 and June 2014. 1579 high-risk patients with AF with suboptimal anticoagulation (either not taking any anticoagulation or taking warfarin but with a low time-in-therapeutic-range) were invited for review, with 86% attending. Of 1063 eligible patients on no anticoagulation, 1020 (96%) agreed to start warfarin (459 (43%)) or a non-vitamin K antagonist oral anticoagulant (NOAC, 561 (53%)). The overall proportion of eligible patients receiving anticoagulation improved from 77% to 95% (p<0.0001). Additionally, 111/121 (92%) patients suboptimally treated with warfarin agreed to switch to a NOAC. Audit of eight practices after 195 (185–606) days showed that 90% of patients started on a new anticoagulant therapy had continued treatment. Based on data extrapolated from previous studies, around 30–35 strokes per year may have been prevented in these previously under-treated high-risk patients.ConclusionsSystematic identification of patients with AF with high stroke-risk and consultation in PCAF consultant-led clinics effectively delivers oral anticoagulation to high-risk patients with AF in the community.
Realising their potential? Exploring interprofessional perceptions and potential of the advanced practitioner role: a qualitative analysis
Authors: Jones Aled , Powell Tom , Watkins Dianne , Kelly Daniel 
Published: December 2015

ObjectivesTo explore perceptions of the current practice and future potential of advanced practitioners (APs) from the perspectives of different professional groups in Wales UK.DesignA qualitative study consisting of nine focus group interviews.MethodsInitially verbatim transcriptions of each focus group interviews were analysed thematically before themes were merged to represent perceptions for the whole data set.ParticipantsData were gathered from a total of 67 stakeholders—including APs from a variety of professional groups (eg, nursing, physiotherapy, paramedics) as well as managers, workforce developers, educators and medical staff who have a role developing and supporting APs in practice.ResultsThe results are presented in four themes: (1) demand, policy context and future priorities, (2) role clarity and standardisation, (3) agreement and understanding of the role and (4) interprofessional working. The context within which current and future AP roles were considered was influenced by inexorable demands for healthcare and the requirements to meet health policy priorities. Developing AP roles were hampered currently by a lack of shared understanding and ‘joined-up’ working between different groups such as medical practitioners, managers, commissioners and educators.ConclusionsFor the AP role to flourish more ‘joined-up’ thinking, support and development opportunities are required between APs, managers, senior clinicians, commissioners and educators. Working together to plan and deliver education, innovation and service delivery is of prime importance to meeting ever increasing complex health needs. This will ensure that future APs are adequately prepared and supported to reach their full potential and help deliver necessary innovations in current models of care delivery.
High prevalence of haemoglobin S in the closed Egyptian community of Siwa Oasis
Authors: Moez Pacinte , Younan Doreen Nazeih Assaad 
Published: December 2015

BackgroundSickle cell haemoglobinopathy, the most frequent of the hereditary anomalies of haemoglobin, occurs most commonly in individuals of African descent. With a population of about 23 000, Siwa Oasis is situated in the Western Desert of Egypt, close to the Libyan border. It is Egypt's most remote oasis town and the Siwans have developed their own distinct Berber culture. Siwans represent a closed isolated community suffering from various health problems, among which is haemolytic anaemia.ObjectivesThis study aimed at screening primary school children of Siwa Oasis for abnormal haemoglobin (Hb) profiles and determining the prevalence of Hb S among them.Materials and methodsThis descriptive and analytic study included 349 primary school children of both sexes, 153 males and 196 females with a male to female ratio of 1:1.3. Their ages ranged between 6 and 12 years. All subjects were screened for abnormal Hbs using complete blood counts and capillary Hb electrophoresis.ResultsOut of a total of 349 primary school children screened, 22% (77/349) were having abnormal Hb profiles, of whom 88% (68/77) had Hb S (ie, sickle cell disorder) constituting 20% of the total population studied. 94% of those having Hb S (64/68) had sickle cell trait (ie, Hb S less than 50%) constituting 18% of the total population screened, while 6% had sickle cell disease, having more than 50% Hb S.ConclusionsThe closed Egyptian community in Siwa Oasis has a high frequency of Hb S carriers and so represents one of the targets of prevention programmes to be implemented in Egypt in order to reduce the economic burden of health services for treating patients with sickle cell disease.Trial registration number1-25/15-1-2014.
Rab11a Mediates Vascular Endothelial-Cadherin Recycling and Controls Endothelial Barrier Function
Authors: Yan Zhibo , Wang Zhen-Guo , Segev Nava , Hu Sanyuan , Minshall Richard D. , Dull Randal O. , Zhang Meihong , Malik Asrar B. , Hu Guochang 
Published: December 2015

Objective—
Vascular endothelial (VE)-cadherin is the predominant component of endothelial adherens junctions essential for cell–cell adhesion and formation of the vascular barrier. Endocytic recycling is an important mechanism for maintaining the expression of cell surface membrane proteins. However, little is known about the molecular mechanism of VE-cadherin recycling and its role in maintenance of vascular integrity.

Approach and Results—
Using calcium-switch assay, confocal imaging, cell surface biotinylation, and flow cytometry, we showed that VE-cadherin recycling required Ras-related proteins in brain (Rab)11a and Rab11 family-interacting protein 2. Yeast 2-hybrid assay and coimmunoprecipitation demonstrated that direct interaction of VE-cadherin with family-interacting protein 2 (at aa 453–484) formed a ternary complex with Rab11a in human endothelial cells. Silencing of Rab11a or Rab11 family-interacting protein 2 in endothelial cells prevented VE-cadherin recycling and VE-cadherin expression at endothelial plasma membrane. Furthermore, inactivation of Rab11a signaling blocked junctional reannealing after vascular inflammation. Selective knockdown of Rab11a in pulmonary microvessels markedly increased vascular leakage in mice challenged with lipopolysaccharide or polymicrobial sepsis.

Conclusions—
Rab11a/Rab11 family-interacting protein 2–mediated VE-cadherin recycling is required for formation of adherens junctions and restoration of VE barrier integrity and hence a potential target for clinical intervention in inflammatory disease.