bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of Residues Responsible for Substrate and Product Specificity of Solanum habrochaites Short-Chain cis-Prenyltransferases
Authors: Kang Jin-Ho , Gonzales-Vigil Eliana , Matsuba Yuki , Pichersky Eran , Barry Cornelius S. 
Published: November 2013

Abstract
Isoprenoids are diverse compounds that have their biosynthetic origin in the initial condensation of isopentenyl diphosphate and dimethylallyl diphosphate to form C10 prenyl diphosphates that can be elongated by the addition of subsequent isopentenyl diphosphate units. These reactions are catalyzed by either cis-prenyltransferases (CPTs) or trans-prenyltransferases. The synthesis of volatile terpenes in plants typically proceeds through either geranyl diphosphate (C10) or trans-farnesyl diphosphate (C15), to yield monoterpenes and sesquiterpenes, respectively. However, terpene biosynthesis in glandular trichomes of tomato (Solanum lycopersicum) and related wild relatives also occurs via the cis-substrates neryl diphosphate (NPP) and 2 Z,6 Z-farnesyl diphosphate (Z,Z-FPP). NPP and Z,Z-FPP are synthesized by neryl diphosphate synthase1 (NDPS1) and Z,Z-farnesyl diphosphate synthase (zFPS), which are encoded by the orthologous CPT1 locus in tomato and Solanum habrochaites, respectively. In this study, comparative sequence analysis of NDPS1 and zFPS enzymes from S. habrochaites accessions that synthesize either monoterpenes or sesquiterpenes was performed to identify amino acid residues that correlate with the ability to synthesize NPP or Z,Z-FPP. Subsequent structural modeling, coupled with site-directed mutagenesis, highlighted the importance of four amino acids located within conserved domain II of CPT enzymes that form part of the second α-helix, for determining substrate and product specificity of these enzymes. In particular, the relative positioning of aromatic amino acid residues at positions 100 and 107 determines the ability of these enzymes to synthesize NPP or Z,Z-FPP. This study provides insight into the biochemical evolution of terpene biosynthesis in the glandular trichomes of Solanum species.
Impact on alcohol purchasing of a ban on multi‐buy promotions: a quasi‐experimental evaluation comparing Scotland with England and Wales
Authors: Nakamura Ryota , Suhrcke Marc , Pechey Rachel , Morciano Marcello , Roland Martin , Marteau Theresa M. 
Published: November 2013

AbstractAimsTo evaluate the impact of the 2011 Scottish ban on multi‐buy promotions of alcohol in retail stores.Design and settingDifference‐in‐differences analysis was used to estimate the impact of the ban on the volume of alcohol purchased by Scottish households, compared with those in England and Wales, between January 2010 and June 2012.ParticipantsA total of 22 356 households in Scotland, England and Wales.MeasurementsRecords of alcohol purchasing from each of four categories (beer and cider, wine, spirits and flavoured alcoholic beverages), as well as total volume of pure alcohol purchased.FindingsControlling for general time trends and household heterogeneity, there was no significant effect of the multi‐buy ban in Scotland on volume of alcohol purchased either for the whole population or for individual socio‐economic groups. There was also no significant effect on those who were large pre‐ban purchasers of alcohol. Most multi‐buys were for beer and cider or for wine. The frequency of shopping trips involving beer and cider purchases increased by 9.2% following the ban (P < 0.01), while the number of products purchased on each trip decreased by 8.1% (P < 0.01). For wine, however, these effects were not significant.ConclusionsBanning multi‐buy promotions for alcohol in Scotland did not reduce alcohol purchasing in the short term. Wider regulation of price promotion and price may be needed to achieve this.
Closed‐loop double‐vasopressor automated system vs manual bolus vasopressor to treat hypotension during spinal anaesthesia for caesarean section: a randomised controlled trial
Authors: Sng B. L. , Tan H. S. , Sia A. T. H. 
Published: November 2013

SummaryHypotension necessitating vasopressor administration occurs commonly during caesarean section under spinal anaesthesia. We developed a novel vasopressor delivery system that automatically administers phenylephrine or ephedrine based on continuous non‐invasive arterial pressure monitoring. A phenylephrine bolus of 50 μg was given at 30‐s intervals when systolic blood pressure fell < 90% of baseline; an ephedrine bolus of 4 mg was given instead if systolic pressure fell < 90% of baseline together with a heart rate < 60 beats.min−1. The control group used manual boluses of either phenylephrine 100 μg or ephedrine 8 mg, administered at 1‐min intervals based on the same thresholds for systolic pressure and heart rate. This randomised, controlled, double‐blinded trial involved 213 healthy women who underwent elective caesarean delivery under spinal anaesthesia using 11 mg hyperbaric bupivacaine with 15 μg fentanyl and 100 μg morphine. The automated vasopressor group had better systolic pressure control, with 37/106 (34.9%) having any beat‐to‐beat systolic pressure reading < 80% of baseline compared with 63/107 (58.9%) in the control group (p < 0.001). There was no difference in the incidence of reactive hypertension, defined as systolic pressure > 120% of baseline, with 8/106 (7.5%) in the automated vasopressor group vs 14/107 (13.1%) in the control group, or total dose of vasopressors. The automated vasopressor group had lower median absolute performance error of 8.5% vs control of 9.8% (p = 0.013), and reduced incidence of nausea (1/106 (0.9%) vs 11/107 (10.3%), p = 0.005). Neonatal umbilical cord pH, umbilical lactate and Apgar scores were similar. Hence, our system afforded better control of maternal blood pressure and reduced nausea with no increase in reactive hypertension when compared with manual boluses.
Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6
Authors: Wantuck J. M. , Ahmed A. , Nguyen M. H. 
Published: November 2013

SummaryBackground The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes.AimTo review characteristics of patients infected with HCV genotypes 4, 5 and 6.MethodsPubMed search for ‘hepatitis C’ AND ‘genotype 4’, ‘hepatitis C’ AND ‘genotype 5’, and ‘hepatitis C’ AND ‘genotype 6’ was conducted and relevant articles were reviewed.ResultsIntravenous drug use is generally responsible for HCV genotype 4 infection in developed countries, but unsafe medical practices cause most cases of HCV genotypes 4, 5 and 6 in endemic countries. The sustained virological response (SVR) rate for patients with HCV genotype 4 who receive pegylated interferon and ribavirin for 48 weeks ranges from 40% to 70% in various small studies. The SVR rate is in the 60–70% range for HCV genotype 5 and 70–80% range for HCV genotype 6 following 48 weeks with pegylated interferon and ribavirin. Preliminary data suggest that a shorter course of 24 weeks of pegylated interferon and ribavirin may be acceptable for HCV genotype 6, with an SVR rate of approximately 70%.ConclusionsThe current standard‐of‐care therapy for HCV genotypes 4, 5 and 6 is pegylated interferon and ribavirin for 48 weeks. A shorter course with 24 weeks of therapy may be considered for patients with genotype 6. Newer and much more effective therapies may be forthcoming in the next few years.
Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage – a placebo‐controlled study
Authors: Bager P. , Dahlerup J. F. 
Published: November 2013

SummaryBackgroundNonvariceal acute upper gastrointestinal bleeding (AUGIB) is often accompanied by post‐discharge anaemia.AimTo investigate whether iron treatment can effectively treat anaemia and to compare a 3‐month regimen of oral iron treatment with a single administration of intravenous iron prior to discharge.MethodsNinety‐seven patients with nonvariceal AUGIB and anaemia were enrolled in a double‐blind, placebo‐controlled, randomised study. The patients were allocated to one of three groups, receiving a single intravenous administration of 1000 mg of iron; oral iron treatment, 200 mg daily for 3 months; or placebo, respectively. The patients were followed up for 3 months.ResultsFrom week 4 onwards, patients receiving treatment had significantly higher haemoglobin levels compared with patients who received placebo only. At the end of treatment, the proportion of patients with anaemia was significantly higher in the placebo group (P < 0.01) than in the treatment groups. Intravenous iron appeared to be more effective than oral iron in ensuring sufficient iron stores.ConclusionsIron treatment is effective and essential for treating anaemia after nonvariceal acute upper gastrointestinal bleeding. The route of iron supplementation is less important in terms of the increase in haemoglobin levels. Iron stores are filled most effectively if intravenous iron supplementation is administered (ClinicalTrials.gov identifier: NCT00978575).
LDL‐c‐linked SNPs are associated with LDL‐c and myocardial infarction despite lipid‐lowering therapy in patients with established vascular disease
Authors: van de Woestijne Anton P. , van der Graaf Yolanda , de Bakker Paul I. W. , Asselbergs Folkert W. , de Borst Gert Jan , Algra Ale , Spiering Wilko , Visseren Frank L. J. ,   the SMART Study Group
Published: November 2013

AbstractBackgroundSeveral single‐nucleotide polymorphisms (SNPs) are associated with both plasma low‐density lipoprotein cholesterol (LDL‐c) level and coronary artery disease in the general population. It is unclear whether these associations also apply to patients with vascular disease and whether the associations are independent of lipid‐lowering therapy.DesignSingle‐nucleotide polymorphisms associated with plasma LDL‐c and vascular risk in the general population (rs11206510 (PCSK9), rs1122608 (LDLR), rs579459 (ABO) and rs599839 (SORT1)) were genotyped in a prospective cohort study of 5482 patients with vascular disease. We determined the association between LDL‐c‐associated alleles and plasma LDL‐c levels and the risk of new vascular events.ResultsAll tested SNPs were associated with LDL‐c plasma levels with a magnitude between +0·06 (95% CI 0·02–0·10) mM and +0·14 (95% CI 0·09–0·18) mM per LDL‐c‐increasing allele. The associations were independent of the use of lipid‐lowering medication, except for rs579459, for which the association was not present in patients using lipid‐lowering medication. In patients with 7–8 risk alleles for these SNPs, 59% of the patients treated with lipid‐lowering medication did not reach the LDL‐c target of <2·5 mM compared with 45% in patients with 3 or fewer risk alleles. LDL‐c‐increasing alleles were not associated with increased risk of vascular events in patients not using lipid‐lowering medication (HRs: 1·01; 95% CI: 0·93–1·09). In patients using lipid‐lowering medication, the risk of myocardial infarction increased with 14% (HRs: 1·14; 95% CI: 1·01–1·28) per allele.ConclusionsIn patients with established vascular disease, the studied SNPs increase LDL‐c plasma levels. LDL‐c‐increasing alleles may be associated with increased risk of myocardial infarction in patients treated with lipid‐lowering medication, but not in patients not treated with lipid‐lowering medication.
Improvement in health‐related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study
Authors: Windyga J. , Lin V. W. , Epstein J. D. , Ito D. , Xiong Y. , Abbuehl B. E. , Ramirez J. H. 
Published: November 2013

SummaryLittle is known about the health‐related quality of life (HRQoL) burden of haemophilia B. The aim of this study was to assess HRQoL burden of haemophilia B, the benefit of recombinant factor IX (rFIX) prophylaxis and the HRQoL benefit of achieving a zero annual bleed rate. Subjects receiving rFIX (BAX326) prophylaxis or on‐demand completed the SF‐36 survey. Baseline SF‐36 scores were compared to the general US population scores to understand the HRQoL burden. Changes in SF‐36 scores between baseline and follow‐up were tested using t‐tests. Subgroup analysis was conducted to examine SF‐36 change among subjects who switched to BAX326 prophylaxis. SF‐36 scores were also compared between those with zero bleeds and those who bled during the study. Compared to the US norms, subjects reported lower average scores in all physical and several mental HRQoL domains. At follow‐up, prophylaxis subjects reported statistically significant and clinically meaningful improvements in overall physical HRQoL, as measured by the Physical Component Score (PCS) (mean change 2.60, P = 0.019), Bodily Pain (BP) (3.45, P = 0.015) and Role Physical (RP) domains (3.47, P = 0.016). Subjects who switched to prophylaxis from intermittent prophylaxis or on‐demand experienced more pronounced improvements not only in the PCS (3.21, P = 0.014), BP (3.71, P = 0.026), RP (4.43, P = 0.008) but also in Vitality (3.71, P = 0.04), Social Functioning (5.06, P = 0.002) and General Health domains (3.40, P = 0.009). Subjects achieving zero bleeds reported lower BP (P = 0.038). Prophylaxis with BAX326 significantly improved HRQoL in patients with moderately severe or severe haemophilia B by reducing bleeds.
Tranexamic acid as adjunct therapy to bypassing agents in haemophiliaApatients with inhibitors
Authors: Tran H. T. T. , Sørensen B. , Rea C. J. , Bjørnsen S. , Ueland T. , Pripp A. H. , Tjønnfjord G. E. , Holme P. A. 
Published: November 2013

SummaryHaemophilia patients with inhibitors require bypassing agents (BPA) like activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) to control bleeds. Adjunct tranexamic acid (TXA) may improve haemostasis. The objective of this study was to investigate safety and haemostatic effect ofTXAgiven in combination withBPA. Healthy volunteers (N = 5) and haemophilia inhibitor patients (N = 6) were enrolled in a prospective case crossover design. Controls were treated withTXA20 mg kg−1orally (O.R.) Patients were treated with aPCC 75 IU kg−1intravenous (I.V.) on day 1 followed byTXA20 mg kg−1O.R. combined with aPCC 75 IU kg−1I.V. on day 2. A 14‐day washout occurred before crossover to rFVIIa 90 μg kg−1I.V. ±TXA. Safety evaluation and blood sampling processes were performed at baseline, 15, 30, 60, 120, 180 and 240 min post treatment. Primary outcome was maximum clot firmness (MCF) evaluated by whole blood thromboelastometry using aTF + tissue plasminogen activator‐based assay. Healthy controls showed a 20‐fold increase inMCFfollowingTXA. AdjunctTXAto aPCC or rFVIIa induced a significant increase inMCF(P < 0.0001) reaching levels indistinguishable from healthy controls treated withTXA(P > 0.05). Infusion of aPCC or rFVIIa alone induced only 3–10 fold increase inMCFfrom baseline, with a decline inMCFstarting after 60–120 min.TXAdid not increase the endogenous thrombin potential. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed. Combination of aPCC or rFVIIa withTXAnormalizes clot stability in haemophilia patients with inhibitor as compared to healthy controls. No clinical or laboratory adverse events were observed.
Stigma towards nurses with mental illnesses: A study of nurses and nurse managers in hospitals in Japan
Authors: Tei‐Tominaga Maki , Asakura Takashi , Asakura Kyoko 
Published: November 2013

AbstractIn the present study, we examined the current situation of nurses with mental illnesses, the stigma associated with these illnesses, and nurses' and nurse managers' perceptions of workplace mental health issues. We conducted a questionnaire survey of 880 nurses and nurse managers in Japan. After we carried out a descriptive analysis to examine the characteristics of stigma, the data of 585 participants were used for comprehensive analyses. In all, 71% of participants reported having worked with nurses with mental illnesses, and 40% reported having supported them. Of the participants, 90% believed a growing number of nurses would have mental illnesses in the near future. Stigma scores were significantly higher for items related to nurses with mental illnesses than for those with physical health problems. There was no significant difference in stigma scores according to sociodemographic and organizational characteristics. Scores for stigma items related to nurses with mental illnesses were significantly higher for participants who had worked with or supported nurses with such illnesses than for those who had not. Our findings suggest that effective approaches are needed to decrease stigma, ensure support in the workplace, and address mental illnesses to counter nurse absenteeism.
Risk factors associated with fatal influenza, Romania, October 2009 – May 2011
Authors: Zolotusca Laurentiu , Jorgensen Pernille , Popovici Odette , Pistol Adriana , Popovici Florin , Widdowson Marc‐Alain , Alexandrescu Viorel , Ivanciuc Alina , Cheng Po‐Yung , Gross Diane , Brown Caroline S. , Mott Joshua A. 
Published: November 2013

BackgroundLimited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations.ObjectivesTo use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory‐confirmed influenza.MethodsRetrospective analysis of case‐based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression.ResultsDuring 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6·6; 95% CI: 3·3–13·1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7·1; 95% CI: 1·6–31·2), clinically obese (OR: 2·9;95% CI: 1·6–31·2), and having an immunocompromising condition (OR: 3·7;95% CI: 1·1–13·4) were significantly associated with fatal outcomes.ConclusionThese findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.
IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp)
Authors: FERRARI G , KING K , RATHBUN K , PLACE C A , PACKARD M V , BARTLETT J A , BOLOGNESI D P , WEINHOLD K J 
Published: November 2013

SUMMARYCD8+ cytotoxic T lymphocytes are an important component in the immunologic control of human viral diseases. IL-7, a stromal cell-derived cytokine, has been demonstrated to enhance both anti-tumour and anti-viral CTL as well as lymphokine-activated killer (LAK) activity. We studied the ability of IL-7 to support the activation and the growth of in vitro antigen-specific CTL precursors (CTLp) present in peripheral blood mononuclear cells (PBMC) from HIV-infected patients. Results from these studies demonstrate that inclusion of IL-7 in a vaccinia/HIV-1 vector-based stimulation strategy greatly augmented overall CTL reactivities, whereas addition of IL-7 to unstimulated cultures failed to induce any significant anti-viral cytolytic activity. In four of six patients, HIV-specific lytic activities were significantly higher in cultures stimulated with antigen plus IL-7 compared with in vitro stimulation (IVS) with antigen alone. Cytotoxic activity was principally mediated by CD8+ effector cells, and CD3+/CD8+ cell expansion was increased by 2–7-fold in the presence of IL-7. In PBMC from seronegative donors, IL-7 enhanced anti-vaccinia CTL activities with less effect on cell proliferation. Furthermore, anti-gag CTL frequencies determined by limiting dilution analysis were increased by 2- and 10-fold in two asymptomatic patients following IVS plus IL-7 compared with antigen stimulation alone. Cytofluorimetric analysis revealed that IL-7 preferentially expanded CD8 memory cells (CD45RO+) and CD8+ lymphocytes expressing activation molecules. IL-7 was also able to support the growth of CD4+ lymphocytes, while having no effect on natural killer (NK)/K lymphocytes. Taken together, these data suggest that IL-7 acts cooperatively with the antigen supporting in vitro maturation of CTLp into functional cytotoxic effectors. Thus IL-7 may be an important biologic entity to consider as part of future immune-based therapies in which ex vivo expansion of antigen-driven CTL is an important determinant.
Heterochrony and post‐natal growth in mammals – an examination of growth plates in limbs
Authors: Geiger M. , Forasiepi A. M. , Koyabu D. , Sánchez‐Villagra M. R. 
Published: November 2013

AbstractMammals display a broad spectrum of limb specializations coupled with different locomotor strategies and habitat occupation. This anatomical diversity reflects different patterns of development and growth, including the timing of epiphyseal growth plate closure in the long bones of the skeleton. We investigated the sequence of union in 15 growth plates in the limbs of about 400 specimens, representing 58 mammalian species: 34 placentals, 23 marsupials and one monotreme. We found a common general pattern of growth plate closure sequence, but one that is universal neither between species nor in higher‐order taxa. Locomotor habitat has no detectable correlation with the growth plate closure sequence, but observed patterns indicate that growth plate closure sequence is determined more strongly through phylogenetic factors. For example, the girdle elements (acetabulum and coracoid process) always ossify first in marsupials, whereas the distal humerus is fused before the girdle elements in some placentals. We also found that heterochronic shifts (changes in timing) in the growth plate closure sequence of marsupials occur with a higher rate than in placentals. This presents a contrast with the more limited variation in timing and morphospace occupation typical for marsupial development. Moreover, unlike placentals, marsupials maintain many epiphyses separated throughout life. However, as complete union of all epiphyseal growth plates is recorded in monotremes, the marsupial condition might represent the derived state.