bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis
Authors: WILLIAMSON Catherine , GORELIK Julia , EATON Bryan M. , LAB Max , SWIET Michael de , KORCHEV Yuri 
Published: August 2015

Obstetric cholestasis is a liver disease of pregnancy that can be complicated by sudden, hitherto unexplained, intra-uterine fetal death. Because intra-uterine death occurs suddenly, and because fetal heart rate abnormalities have been reported in obstetric cholestasis, we hypothesized that intra-uterine death is caused by impaired fetal cardiomyocyte function, resulting in fetal cardiac arrest. Obstetric cholestasis is associated with raised levels of maternal and fetal serum bile acids, and we propose that these may alter cardiomyocyte function. It was not possible to investigate the effects of bile acids on the intact human fetal heart at a cellular level. Therefore we used the closest available model of fetal myocardium at term: a primary culture of neonatal rat cardiomyocytes in which cells beat synchronously and develop pacemaker activity. The effect of the primary bile acid taurocholate (0.3 mM and 3 mM) on cultures of single cardiomyocytes, each with its own independent rate of contraction, was a reversible decrease in the rate of contraction and in the proportion of beating cells (P < 0.001). Addition of taurocholate to a network of synchronously beating cells caused a similar decrease in the rate of contraction. Furthermore, the integrity of the network was destroyed, and cells ceased to beat synchronously. Taurocholate also resulted in altered calcium dynamics and loss of synchronous beating. These data suggest that raised levels of the bile acid taurocholate in the fetal serum in obstetric cholestasis may result in the development of a fetal dysrhythmia and in sudden intra-uterine death.
β2-Adrenoceptor desensitization in human alveolar macrophages induced by inhaled terbutaline in vivo is not counteracted by budesonide
Authors: ZETTERLUND Anita , HJEMDAHL Paul , LARSSON Kjell 
Published: August 2015

In vitro studies suggest that glucocorticoids may counteract β-agonist-induced desensitization of β-adrenoceptors by actions at the transcriptional level, but the clinical relevance of such findings is not clear. Oral terbutaline treatment decreases β-adrenoceptor sensitivity in alveolar macrophages in vivo. This effect is not counteracted by inhaled or orally taken steroids. We therefore examined whether inhaled terbutaline elicited a similar effect on β2-adrenoceptor sensitivity in alveolar macrophages, and if co-treatment with an inhaled steroid, budesonide, would prevent such down-regulation. Bronchoalveolar lavage (BAL) and lung function tests, including bronchodilator responses to inhaled terbutaline, were performed before and after 2 weeks of regular inhalation of terbutaline, 0.5 mg three times daily, and budesonide, 400 µg twice daily, or placebo, in 24 healthy volunteers. Four untreated subjects served as controls. A marked, approx. 90%, decrease in isoprenaline-induced cAMP accumulation in alveolar macrophages was found in both treatment groups after 2 weeks, with no difference between placebo and budesonide (P = 0.45). In the untreated control group, cAMP responses to both isoprenaline and prostaglandin E1 tended to be lower on the second occasion. A limited, non-specific desensitization of adenylate cyclase activity thus contributed to the marked desensitization elicited by terbutaline inhalations. The bronchodilator response to inhaled terbutaline did not change after treatment in any of the three groups (F = 0.9, P = 0.50). In conclusion, inhalation of a β-agonist induced marked down-regulation of β2-adrenoceptor sensitivity in alveolar macrophages in vivo without influencing the bronchodilator response to a β2-agonist in healthy subjects. Co-treatment with an inhaled steroid failed to counteract the desensitization of alveolar macrophage β2-adrenoceptors.
Effects of smoking and abstention from smoking on fibrinogen synthesis in humans
Authors: HUNTER Kirsty A. , GARLICK Peter J. , BROOM Iain , ANDERSON Susan E. , McNURLAN Margaret A. 
Published: August 2015

Cigarette smoking and hyperfibrinogenaemia are both significant risk factors for the development of cardiovascular disease. Two studies are described here which aimed to establish the metabolic mechanism responsible for the raised plasma fibrinogen concentration observed in smokers. Chronic smokers had a significantly elevated absolute rate of fibrinogen synthesis (ASR) compared with non-smokers (22.7±1.3 mg/kg per day versus 16.0±1.3 mg/kg per day; means±S.E.M., P < 0.01), with plasma levels of fibrinogen significantly correlated with fibrinogen synthesis (r = 0.65, P = 0.04). Unlike fibrinogen, plasma albumin concentrations were lower in smokers than in non-smokers (45±0.4 versus 47±0.7 g/l, P < 0.05), but there was no difference in rates of albumin synthesis between the two groups. Two weeks cessation from smoking by previously chronic smokers was associated with a rapid and marked fall in plasma fibrinogen concentration (from 3.06±0.11 g/l to 2.49±0.14 g/l, P < 0.001), and a significant reduction in ASR (a 33% reduction, from 24.1±1.7 to 16.1±1.0 mg/kg per day, P < 0.001). These studies suggest a primary role for increased synthesis in producing the hyperfibrinogenaemia associated with smoking. Moreover, abstention from smoking for a period of only 2 weeks induces a significant decrease in the rate of fibrinogen synthesis by the liver, with a concomitant reduction in the plasma fibrinogen concentration.
Gender differences in protein kinase G-mediated vasorelaxation of rat aorta
Authors: TEEDE Helena , VAN DER ZYPP Andrea , MAJEWSKI Henryk 
Published: August 2015

Although gender and oestrogen treatment influence production of the vasorelaxant, NO, their influence on factors downstream in the NO signal-transduction pathway, specifically protein kinase G (PKG), remains unknown. We aimed to study the influence of sex hormones on PKG, along with the endothelial modulation of these effects, in rat thoracic aortic rings in two separate groups, control male and female rats and ovariectomized female rats after treatment with oestrogen or vehicle. Vessel preparations were preconstricted with phenylephrine (0.1 μM). Constrictions were greater in male than female aortas. This differential effect was attenuated by endothelium removal, addition of the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1μM) and the nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (l-NMMA, 100 μM), supporting the role of NO in maintenance of basal relaxation and vascular tone in females. We have examined the relative activity of the specific PKG subtypes 1α and 1β in vascular smooth muscle, based on relaxation of rat aortas by two cGMP analogues with different selectivity, β-phenyl-l-N2-ethano-8-bromo-cGMP (8-Br-PET-cGMP) and 8-(2-aminophenylthio)cGMP (8-APT-cGMP). 8-Br-PET-cGMP was more potent than 8-APT-cGMP in both sexes, suggesting that PKG 1α is the primary subtype involved in vasorelaxation. The gender differences in PKG activity were examined based on relaxation responses in male and female rat aortas. Both 8-Br-PET-cGMP and 8-APT-cGMP were more potent in aortas from male than female rats. In further studies on the endothelial modulation of relaxation with 8-APT-cGMP, the differential gender-vasorelaxation response was negated by endothelium removal and addition of the guanylate cyclase inhibitor ODQ (1 μM), but not by the NOS inhibitor l-NMMA (100 μM), suggesting that an endothelial-dependent factor other than NO may be responsible for the observed differential PKG-mediated vasorelaxation between the sexes. To further investigate oestrogen influence on PKG, treated female rats were studied. Contrary to our hypothesis, in the presence of 1 μM ODQ, there were no differences in either the phenylephrine constriction, or the relaxation with 8-APT-cGMP from either sham-operated, vehicle-treated or oestrogen-treated ovariectomized rats. In conclusion, female rat aortas have greater basal NO production compared with males. Relaxant responses to PKG activation are greater in aortas from male compared with female rats. These findings suggest hormonal regulation of PKG; however, oestrogen treatment of ovariectomized rats did not affect PKG activity, suggesting factors other than oestrogen may be responsible for the gender differences noted in this study.
Increased levels of typically fetal bile acid species in patients with hepatocellular carcinoma
Authors: EL-MIR Mohamad Y. , BADIA Maria D. , LUENGO Nazaret , MONTE Maria J. , MARIN Jose J. G. 
Published: August 2015

The aim of this work was to investigate the reappearance during liver neoplasia of bile acids (BAs) species, which are unusual in healthy adults, but common in fetuses. Serum and urine samples were collected from patients with hepatocellular carcinoma (HCC; n = 27), and for comparative purposes, with liver cirrhosis (n = 49), liver metastasis (n = 19), chronic viral hepatitis (n = 11) and healthy volunteer (control group; n = 26) groups. BAs were identified and measured by GC–MS. Hypercholanaemia was found in all groups of patients. In HCC, this was characterized by a marked increase in the chenodeoxycholate/cholate ratio in both serum and urine. Although increased levels of BAs, with hydroxylations at unusual positions, and oxo-BAs were found in HCC, these were not significantly different from those observed in other groups. However, BAs with a flat structure, i.e. Δ4-unsaturated- and 5α- or allo-BAs, which were almost absent in healthy subjects, were markedly increased in the serum and urine of HCC patients. They were also detected, although in much lower amounts, in liver metastasis and liver cirrhosis, but not in viral hepatitis. Flat-BAs were better detected in urine than in serum. Urinary Δ4-unsaturated-BA output was significantly lower in patients with small tumours (< 3 cm) compared with those with higher size tumours. No correlation between flat-BA output into urine and serum alpha-fetoprotein or total BAs was found. These results suggest that Δ4- and/or allo-BAs are particularly elevated in patients with HCC, which may be a potentially useful complementary, rather than alternative, marker for early detection of liver neoplasia.
Effects of prior moderate exercise on exogenous and endogenous lipid metabolism and plasma factor VII activity
Authors: GILL Jason M. R. , FRAYN Keith N. , WOOTTON Stephen A. , MILLER George J. , HARDMAN Adrianne E. 
Published: August 2015

Moderate exercise reduces postprandial triacylglycerol concentrations, which are a risk marker for coronary heart disease. The present study sought to determine the qualitative nature of exercise-induced changes in lipid metabolism and their association (if any) with changes in factor VII activation. Eleven normotriglyceridaemic men, aged 51.7±6.1 years (mean±S.D.), participated in two oral fat tolerance tests after different pre-conditions: control (no exercise), and exercise (90 min of brisk walking the day before). Venous blood samples were obtained in the fasted state and for 8 h after ingestion of a high-fat meal (1.32 g of fat, 1.36 g of carbohydrate, 0.30 g of protein and 10 mg of [1,1,1-13C] tripalmitin·kg-1 body mass). Prior exercise reduced postprandial plasma triacylglycerol concentrations by 25±3% (mean±S.E.M.), with lower concentrations in the Svedberg flotation rate (Sf) 20–400 (very-low-density lipoprotein) fraction accounting for 79±10% of this reduction. There was no effect on plasma factor VII coagulant activity or on the concentration of the active form of factor VIIa. Prior exercise increased postprandial serum 3-hydroxybutyrate and plasma fatty acid concentrations, decreased serum postprandial insulin concentrations and increased exogenous (8 h 13C breath excretion of 15.1±0.9% of ingested dose compared with 11.9±0.8%; P = 0.00001) and endogenous postprandial fat oxidation. These data raise the possibility that reduced hepatic secretion of very-low-density lipoprotein plays a role in the attenuation of plasma triacylglycerol concentrations seen after exercise, although it is possible that increased triacylglycerol clearance also contributes to this effect.
Influence of an inducible nitric oxide synthase promoter variant on clinical variables in patients with coronary artery disease
Authors: MORRIS Brian J. , GLENN Cheryl L. , WILCKEN David E. L. , WANG Xing Li 
Published: August 2015

Pathophysiological processes in coronary artery disease (CAD) are influenced by genetic factors. Since (i) inducible nitric oxide synthase (iNOS) has important cardiovascular effects, and (ii) the promoter of the iNOS gene (NOS2A) is genetically modulated by a 4 bp insertion/deletion (+/-) polymorphism located 0.7 kb upstream, we decided to examine the influence of this variant on clinical variables in 856 CAD patients of Anglo-Celtic/Northern European extraction. We found that 2% of CAD patients were homozygous for the + allele, and 19% were heterozygous. Males made up 74% of the patient group, and in these the + allele was associated with 38% higher plasma glucose levels (P = 0.005), a 4.8% elevation in the waist/hip ratio (P = 0.009) and a 48% greater frequency of unstable angina (P = 0.014). The + allele, by influencing iNOS expression, could thus contribute to indices of insulin resistance and angina severity in male CAD patients.
Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays
Authors: BELGORE Funmi M. , BLANN Andrew D. , LIP Gregory Y. 
Published: August 2015

Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. VEGF interacts with the endothelium via two membrane-spanning receptors, fms-like tyrosine kinase (Flt)-1 and kinase domain receptor. A soluble form of Flt-1 (sFlt-1) was isolated from endothelial cell media; however, its biological significance is still unknown, with limited data on plasma sFlt-1 levels in disease states. We have developed two new ELISAs for detecting free and VEGF-complexed sFlt-1, which were tested in accordance with standard validation and assessment methodologies employed in commercial settings. The intra-and inter-assay coefficients of variation are < 5% and 10% respectively, and results are highly reproducible. Applying these ELISAs in a clinical setting, we measured levels of VEGF, free and complexed sFlt-1 in citrated plasma from 40 patients with cardiovascular disease and 40 healthy controls. Median (interquartile range) plasma levels of VEGF in patients were significantly greater than controls [403 pg/ml (158–925 pg/ml) versus 113 pg/ml (33–231 pg/ml), P ⩽ 0.05]. Free sFlt-1 was significantly lower in patients compared with controls [8 ng/ml (2–22 ng/ml) versus 21 ng/ml (10–73 ng/ml), P ⩽ 0.05]. There was no significant difference in the levels of complexed sFlt-1 between the two groups. Plasma levels of VEGF-complexed sFlt-1 are minimal, despite the presence of excess free sFlt-1. Thus unbound plasma VEGF detected by ELISA may represent the majority of circulating VEGF, and justifies the measurement of plasma VEGF as an indicator of circulating VEGF levels. Furthermore, these results suggest that circulating sFlt-1 may serve as a selective inhibitor of VEGF activity, and that this regulatory mechanism may be altered by pathological conditions.
SurvCurv database and online survival analysis platform update
Authors: Ziehm Matthias , Ivanov Dobril K. , Bhat Aditi , Partridge Linda , Thornton Janet M. 
Published: August 2015

AbstractSummary: Understanding the biology of ageing is an important and complex challenge. Survival experiments are one of the primary approaches for measuring changes in ageing. Here, we present a major update to SurvCurv, a database and online resource for survival data in animals. As well as a substantial increase in data and additions to existing graphical and statistical survival analysis features, SurvCurv now includes extended mathematical mortality modelling functions and survival density plots for more advanced representation of groups of survival cohorts.Availability and implementation: The database is freely available at https://www.ebi.ac.uk/thornton-srv/databases/SurvCurv/. All data are published under the Creative Commons Attribution License.Contact: matthias.ziehm@ebi.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Avoid Endoscopy in Children With Suspected Inflammatory Bowel Disease Who Have Normal Calprotectin Levels
Authors: Heida Anke , Holtman Gea A. , Lisman‐van Leeuwen Yvonne , Berger Marjolein Y. , van Rheenen Patrick F. 
Published: August 2015

ABSTRACTIn children with suspected inflammatory bowel disease, adding calprotectin stool testing to the screening strategy has been recommended to distinguish organic from nonorganic disease. In this cohort study with historical controls, we could not confirm that screening with stool calprotectin improves the diagnostic yield (ratio inflammatory bowel disease–positive endoscopies and total number of endoscopies); however, in patients with normal fecal calprotectin levels (<50 μg/g) endoscopic and histological abnormalities were not seen. We propose to refrain from endoscopy when stool calprotectin levels are normal.
Do teachers misbehave? Aggression in school teams
Authors: Ben Sasson Dvora , Somech Anit 
Published: August 2015

Purpose– Despite growing research on school aggression, significant gaps remain in the authors’ knowledge of team aggression, since most studies have mainly explored aggression on the part of students. The purpose of this paper is to focus on understanding the phenomenon of workplace aggression in school teams. Specifically, the purpose of the study was to examine whether team affective conflict in school teams mediates the relationship between team injustice climate (distributive, procedural, and interpersonal injustice climate) and team aggression.Design/methodology/approach– Data were collected from a survey of 43 school teams at different schools using questionnaires.Findings– Results showed that team affective conflict played a role in fully mediating the relationship of team procedural and interpersonal injustice climate to team aggression.Research limitations/implications– The present results empirically support the notion that workplace aggression can be considered not only an individual phenomenon but also a team phenomenon. Furthermore, it highlights the significance of organizational factors in predicting this phenomenon. The study should serve to encourage principals to reduce the level of team aggression and develop a supportive climate characterized by fair procedures and respect.Originality/value– A review of the literature also reveals that little investigative effort has been made by scholars to examine aggression on the part of teachers. Evidence for this can be seen in the scarcity of publications on this topic. The current literature’s call to address this issue in schools and at the team level (Fox and Stallworth, 2010) stimulated the present study by highlighting the importance of exploring the contextual factors, rather than the individual ones, responsible for school team aggression.
Characteristics of teacher incentive pay programs: a statewide district survey
Authors: Liang Guodong , Akiba Motoko 
Published: August 2015

Purpose– The purpose of this paper is to examine the characteristics of teacher incentive pay programs used by midsize to large school districts in Missouri.Design/methodology/approach– This study primarily used the Teacher Compensation Programs (TCP) survey data. The TCP survey was developed by the authors to understand the nature and characteristics of financial incentives that Missouri districts used to recruit, reward, and retain quality teachers.Findings– The data showed that, during the 2009-2010 academic year, 32 percent of the districts offered at least one financial incentive to recruit or retain teachers. Districts were more likely to reward teachers for obtaining National Board certification and for assuming extra duties than for teaching in the subject areas of shortage or in hard-to-staff schools. Larger districts with higher teacher salary were more likely than small districts to offer a larger number of incentive pay programs.Originality/value– The findings of this study advance our knowledge of local incentive pay policies. It also contributes to the global discourse of teacher compensation and incentives and can be informative to policymakers in the USA and around the world when designing and implementing incentive pay programs to teachers. Further, it sheds light on the important policy question of whether disadvantaged local educational agencies are more likely to use incentive pay programs to recruit and retain teachers and promote an equitable distribution of the teacher workforce. This informs the decision making of providing targeted support to those in need.
Migrating to the cloud
Authors: Doherty Eileen , Carcary Marian , Conway Gerard 
Published: August 2015

Purpose
– Cloud computing is a relatively new phenomena. It has rarely been examined in the context of the small to medium-sized enterprises (SMEs). The purpose of this paper is to examine the drivers and barriers to cloud computing adoption by SMEs in Ireland.

Design/methodology/approach
– This study adopted an exploratory approach. A quantitative approach was adopted in the data collection phase. An online self-completion questionnaire was distributed by e-mail to 1,500 SMEs in Ireland. A response rate of 6 per cent was achieved generating 95 usable responses.

Findings
– Findings from this study indicate that Irish SMEs are adopting cloud technology. The key driver identified is the resultant cost benefits for the firm. However, concern over continuous availability of the service is identified by the SME as a key challenge and is hindering widespread adoption of cloud technology.

Research limitations/implications
– This study whilst exploratory in nature, has laid the foundation for further research in the area of cloud computing adoption. This research should enable further studies to replicate this process with the possibility of extending the study to include other countries, on a larger scale and with a particular focus on the knowledge intensive business services sector. This study would benefit from adding a qualitative perspective to the research topic to add depth and enhance the “richness” of the data collected during the process.

Practical implications
– This study concludes that policy makers and cloud providers need to provide assurances to SMEs over issues of continuous availability of the cloud service through increased and on-going investment in a high-speed, broadband infrastructure and through ensuring issues pertaining to standardization and compliance are resolved.

Originality/value
– This exploratory research has illuminated this area through examining the drivers and barriers to cloud adoption by SMEs. In the Irish context, the benefits of engaging in such activity can reap many benefits. Of particular importance to a peripheral economy such as Ireland is the value of adopting cloud computing which is central to offering competitive advantage and controlling costs.