bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic– pharmacodynamic analysis of the role of CYP2C19 genotypes in short‐term rabeprazole‐based triple therapy againstHelicobacter pylori
Authors: Yang Jyh‐Chin , Yang Yu‐Fan , Uang Yow‐Shieng , Lin Chun‐Jung , Wang Teh‐Hong 
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Asians have a higher percentage of CYP2C19 poor metabolizers (PMs) and a high percentage ofHelicobacter pyloriinfection compared with Whites.• Although rabeprazole has been suggested to be least affected by CYP2C19 genotype, the pharmacokinetic properties of rabeprazole have been shown to correlate with the CYP2C19 genotype.• Short‐term (i.e. <7 days) rabeprazole‐based triple therapy has been suggested for its use in eradicatingH. pylori, whereas the eradication rate has been reported variously as 90–27% without CYP2C19 genotyping.WHAT THIS STUDY ADDS• Population pharmacokinetic–pharmacodynamic analysis showed that the plasma rabeprazole levels, the values ofkeo(the first‐order rate constant for drug dissipation from the effect compartment), and the predicted gastrin‐time profile were higher in CYP2C19 PMs than in extensive metabolizers (EMs) after multiple dosing.• Helicobacter pyloriwas eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain, whereas the eradication rates ranged from 58 to 85% in CYP2C19 EMs.AIMSThe aim was to explore the role of CYP2C19 polymorphism in short‐term rabeprazole‐based triple therapy againstHelicobacter pyloriinfection.METHODSPatients withH. pyloriinfection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1–4, days 4–7, or days 1–7. A direct link model with an effect compartment was used in the population pharmacokinetic–pharmacodynamic analysis. The status ofH. pyloriinfection was evaluated.RESULTSRabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7vs.16.8 l h−1in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC50andkeoof gastrin response increased with multiple doses of rabeprazole. Thekeovalues were lower in CYP2C19 PMs than in EMs on day 1 (0.012vs.0.017 × 10−4 l min−1), and higher than in EMs on day 4 (0.804vs.0.169 × 10−4 l min−1) of rabeprazole treatment. The predicted gastrin‐time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7.Helicobacter pyloriwas eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%.CONCLUSIONSCYP2C19 genotypes play a role inH. pylorieradication therapy. Rabeprazole‐based short‐term triple therapy may be applicable in CYP2C19 PMs forH. pylorieradication.
Do educational interventions improve prescribing by medical students and junior doctors? A systematic review
Authors: Ross Sarah , Loke Yoon K 
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Recent studies have identified a problem with prescribing errors in hospitals.• It is unclear to what extent educational interventions improve prescribing performance. WHAT THIS STUDY ADDS • A wide range of interventions have been tested, but most of them have been on small numbers of participants in single centres.• The most widely tested intervention, with the greatest number of randomized controlled trials, is the WHO Good Prescribing Guide, which has demonstrated efficacy in international settings across a wide range of students.• Further work is needed to produce high‐quality educational interventions and robust evaluations.Our aim was to review systematically the literature on educational interventions to improve prescribing by medical students and junior doctors. MEDLINE, EMBASE, Educational Resource Information Center, British Education Index, PsycINFO, CINAHL, TIMELIT, Cochrane Trials Database and grey literature were searched. Inclusion criteria were: educational interventions to improve medical student and/or junior doctors' prescribing, in primary or secondary care settings, and published after 1990. After screening 3189 records, we retrieved 11 controlled and four ‘before‐and‐after’ trials. Ten controlled trials showed improvements in the scores of the intervention group on written scenarios or clinical examination stations, but one study in junior doctors showed no effect on real‐life prescription errors. Only one intervention [the World Health Organization (WHO) Good Prescribing Guide, in six randomized trials] had been tested in a variety of international settings and across a range of students at different levels. All four ‘before‐and‐after’ trials reported significant improvements in written tests or clinical stations. However, most studies tested only small numbers of participants and were affected by a range of methodological flaws. There is only moderate evidence in the literature to inform medical schools about how to prepare medical students for the challenges of prescribing. The WHO Good Prescribing Guide is the only model that has been widely used and shown to improve prescribing. Although it is based on sound principles, there is a need for further development. Robust methods of assessment are required to show clearly whether particular teaching interventions are successful.
Textilinin‐1, an alternative anti‐bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss
Authors: Flight Simone M. , Johnson Lambro A. , Du Qianyun S. , Warner Roscoe L. , Trabi Manuela , Gaffney Patrick J. , Lavin Martin F. , De Jersey John , Masci Paul P. 
Published: February 2009

SummaryAprotinin has been used widely in surgery as an anti‐bleeding agent but is associated with a number of side effects. We report that textilinin‐1, a serine protease inhibitor from Pseudonaja textilis venom with sequence relatedness to aprotinin, is a potent but reversible plasmin inhibitor and has a narrower range of protease inhibition compared to aprotinin. Like aprotinin, textilinin‐1 at 5 μmol/l gave almost complete inhibition of tissue plasminogen activator‐induced fibrinolysis of whole blood clots. The activated partial thromboplastin time for plasma was markedly increased by aprotinin but unaffected by textilinin‐1. In a mouse tail‐vein bleeding model, intravenous textilinin‐1 and aprotinin caused similar decreases in blood loss but time to haemostasis in the textilinin‐treated animals was significantly shorter than in aprotinin‐treated mice. Based on these data, textilinin‐1 merits further investigation as a therapeutic alternative to aprotinin.
Beneficial and harmful effects of anthracyclines in the treatment of childhood acute lymphoblastic leukaemia: a systematic review and meta‐analysis
Authors: Childhood Acute Lymphoblastic Leukaemia Collaborative Group  
Published: February 2009

SummaryAnthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non‐randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta‐analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non‐significantly, non‐bone marrow relapse, resulting in an increased relapse‐free interval. However there was a non‐significant increase in induction failures, and in deaths in first remission. Event‐free survival at 5 years was 56·7% with anthracycline versus 52·8% without (Odds Ratio = 0·91; 95% Confidence Interval = 0·76–1·10; P = 0·3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences.
Ice age distributions of European small mammals: insights from species distribution modelling
Authors: Fløjgaard Camilla , Normand Signe , Skov Flemming , Svenning Jens‐Christian 
Published: February 2009

AbstractAim  In addition to the traditionally recognized Last Glacial Maximum (LGM, 21 ka) refuge areas in the Mediterranean region, more northerly LGM distributions for temperate and boreal taxa in central and eastern Europe are increasingly being discussed based on palaeoecological and phylogeographical evidence. Our aim was to investigate the potential refuge locations using species distribution modelling to estimate the geographical distribution of suitable climatic conditions for selected rodent species during the LGM.Location  Eurasia.Methods  Presence/absence data for seven rodent species with range limits corresponding to the limits of temperate or boreal forest or arctic tundra were used in the analysis. We developed predictive distribution models based on the species present‐day European distributions and validated these against their present‐day Siberian ranges. The models with the best predictors of the species distributions across Siberia were projected onto LGM climate simulations to assess the distribution of climatically suitable areas.Results  The best distribution models provided good predictions of the present‐day Siberian ranges of the study species. Their LGM projections showed that areas with a suitable LGM climate for the three temperate species (Apodemus flavicollis, Apodemus sylvaticus and Microtus arvalis) were largely restricted to the traditionally recognized southern refuge areas, i.e. mainly in the Mediterranean region, but also southernmost France and southern parts of the Russian Plain. In contrast, suitable climatic conditions for the two boreal species (Clethrionomys glareous and Microtus agrestis) were predicted as far north as southern England and across southern parts of central and eastern Europe eastwards into the Russian Plain. For the two arctic species (Lemmus lemmus and Microtus oeconomus), suitable climate was predicted from the Atlantic coast eastward across central Europe and into Russia.Main conclusions  Our results support the idea of more northerly refuge areas in Europe, indicating that boreal species would have found suitable living conditions over much of southern central and eastern Europe and the Russian Plain. Temperate species would have primarily found suitable conditions in the traditional southern refuge areas, but interestingly also in much of the southern Russian Plain.
Fatty acid acylation regulates trafficking of the unusual Plasmodium falciparum calpain to the nucleolus
Authors: Russo Ilaria , Oksman Anna , Goldberg Daniel E. 
Published: February 2009

SummaryThe Plasmodium falciparum genome encodes a single calpain. By generating P. falciparum clones expressing C‐terminally tagged calpain, we localized this protein to the nucleolus. Pf_calpain possesses an unusual and long N‐terminal domain in which we identified three subregions that are highly conserved among Plasmodium species. Two have putative targeting signals: a myristoylation motif and a nuclear localization sequence. We assessed their functionality. Our data show that the nuclear localization sequence is an active nuclear import motif that contains an embedded signal conferring nucleolar localization on various chimeras. The N‐terminus is myristoylated at Gly2 and palmitoylated at Cys3 and Cys22. Palmitoylation status has an important role in dictating P. falciparum calpain localization. The targeting signals function in mammalian cells as well as in the parasite. P. falciparum calpain is a unique nucleolar protein with an interesting mechanism of targeting.
Genome‐wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress
Authors: Enjalbert Brice , Moran Gary P. , Vaughan Claire , Yeomans Tim , MacCallum Donna M. , Quinn Janet , Coleman David C. , Brown Alistair J. P. , Sullivan Derek J. 
Published: February 2009

Summary Candida albicans is more pathogenic than Candida dubliniensis. However, this disparity in virulence is surprising given the high level of sequence conservation and the wide range of phenotypic traits shared by these two species. Increased sensitivity to environmental stresses has been suggested to be a possible contributory factor to the lower virulence of C. dubliniensis. In this study, we investigated, in the first comparison of C. albicans and C. dubliniensis by transcriptional profiling, global gene expression in each species when grown under conditions in which the two species exhibit differential stress tolerance. The profiles revealed similar core responses to stresses in both species, but differences in the amplitude of the general transcriptional responses to thermal, salt and oxidative stress. Differences in the regulation of specific stress genes were observed between the two species. In particular, ENA21, encoding a sodium ion transporter, was strongly induced in C. albicans but not in C. dubliniensis. In addition, ENA21 was identified in a forward genetic screen for C. albicans genomic sequences that increase salt tolerance in C. dubliniensis. Introduction of a single copy of CaENA21 was subsequently shown to be sufficient to confer salt tolerance upon C. dubliniensis.
CRISPR families of the crenarchaeal genus Sulfolobus: bidirectional transcription and dynamic properties
Authors: Lillestøl Reidun K. , Shah Shiraz A. , Brügger Kim , Redder Peter , Phan Hien , Christiansen Jan , Garrett Roger A. 
Published: February 2009

SummaryClusters of regularly interspaced short palindromic repeats (CRISPRs) of Sulfolobus fall into three main families based on their repeats, leader regions, associated cas genes and putative recognition sequences on viruses and plasmids. Spacer sequence matches to different viruses and plasmids of the Sulfolobales revealed some bias particularly for family III CRISPRs. Transcription occurs on both strands of the five repeat‐clusters of Sulfolobus acidocaldarius and a repeat‐cluster of the conjugative plasmid pKEF9. Leader strand transcripts cover whole repeat‐clusters and are processed mainly from the 3′‐end, within repeats, yielding heterogeneous 40–45 nt spacer RNAs. Processing of the pKEF9 leader transcript occurred partially in spacers, and was incomplete, probably reflecting defective repeat recognition by host enzymes. A similar level of transcripts was generated from complementary strands of each chromosomal repeat‐cluster and they were processed to yield discrete ∼55 nt spacer RNAs. Analysis of the partially identical repeat‐clusters of Sulfolobus solfataricus strains P1 and P2 revealed that spacer‐repeat units are added upstream only when a leader and certain cas genes are linked. Downstream ends of the repeat‐clusters are conserved such that deletions and recombination events occur internally.
Effects of mitochondrial complex III disruption in the respiratory chain of Neurospora crassa
Authors: Duarte Margarida , Videira Arnaldo 
Published: February 2009

SummaryIn mitochondria from most organisms, including Neurospora crassa, dimeric complex III was found associated with complex I. Additional association of complex IV with this core structure leads to the formation of a respirasome. It was recently described for bacteria and mammals that complex III is needed for the assembly/stability of complex I. To elucidate the role of complex III in the organization of the respiratory chain of N. crassa, we analysed strains devoid of either the Rieske iron‐sulphur or the COREII polypeptide subunits. The mutants display reduced growth, are female sterile and lack active complex III. The supramolecular organization of the oxidative phosphorylation system was characterized by electrophoretic analyses and the efficiency of the respiratory chain analysed by oxygen consumption measurements. The results obtained indicate that absence of complex III activity is not associated with the absence of complex I or complex IV, and leads to the induction of alternative oxidase. Complex III mutant mitochondria are devoid of respirasomes but contain significant amounts of dimeric complex I (I2) and of the supercomplex I1IV1. Moreso, for the first time the alternative oxidase was found associated with dimeric complex IV and with supercomplex I1IV1.
Modelling the formation of residual dune ridges behind barchan dunes in North‐east Brazil
Authors: LEVIN NOAM , TSOAR HAIM , HERRMANN HANS JÜRGEN , MAIA LUIS P. , CLAUDINO‐SALES VANDA 
Published: February 2009

AbstractResidual dune ridges are often formed by vegetation growing along a line some distance upwind of the lower stoss slope of migrating dunes. This process is common in areas where vegetation germinates along the edge of the water during the rainy period when the water level is higher and interdune areas are flooded. The phenomenon occurs on a large scale in North‐east Brazil, because of the rise and fall in groundwater level at the end of the rainy season. Each residual dune ridge corresponds to the position of the dune during the wet period in each year. Therefore, variations in the distance between these residual dune ridges could be used potentially to monitor climatic fluctuations in rainfall and wind. To examine the potential use of these residual dune ridges for the reconstruction of past climatic fluctuations, a model that simulates them under varying conditions of wind, rainfall and evaporation rates was formulated. The model was tested for sensitivity to climatic variability in North‐east Brazil and validated against residual dune ridge displacements as measured in the field and from high spatial resolution satellite images. Based on the results, it is concluded that residual dune ridges may not form in North‐east Brazil in years which are exceptionally dry, as may happen during El‐Niño events. When this type of event happens, the distance between adjacent residual dune ridges corresponds to more than one year and, therefore, the correlation between dune displacements and wind power becomes weak or even disappears. Additionally, because of biotic, aeolian and hydrological processes, these arcuate residual dune ridges may not preserve their initial shape for long periods. The presence of residual dune ridges testifies to the temporary flooding which may or may not be seasonal. However, the potential for using residual dune ridges to reconstruct the palaeo‐climate of wind regime on a yearly basis or to identify past El‐Niño events seems to be limited.
The household costs of health care in rural South Africa with free public primary care and hospital exemptions for the poor
Authors: Goudge Jane , Gilson Lucy , Russell Steve , Gumede Tebogo , Mills Anne 
Published: February 2009

SummaryObjective  To measure the direct cost burdens (health care expenditure as a percent of total household expenditure) for households in rural South Africa, and examine the expenditure and use patterns driving those burdens, in a setting with free public primary health care and hospital exemptions for the poor.Methods  Data on illness events, treatment patterns and health expenditure in the previous month were assessed from a cross‐sectional survey of 280 households conducted in the Agincourt Health and Demographic Surveillance site, South Africa.Results  On average, a household experiencing illness incurred a direct cost burden of 4.5% of total household expenditure. A visit to a public clinic generated a mean burden of 1.3%. Complex sequences of treatments led 20% of households to incur a burden over 10%, with transport costs generating 42% of this burden. An outpatient public hospital visit generated a burden of 8.2%, as only 58% of those eligible obtained an exemption; inpatient stays incurred a burden of 45%. Consultations with private providers incurred a mean burden of 9.5%. About 38% of individuals who reported illness did not take any treatment action, 55% of whom identified financial and perceived supply‐side barriers as reasons.Conclusion  The low overall mean cost burden of 4.5% suggests that free primary care and hospital exemptions provided financial protection. However, transport costs, the difficulty of obtaining hospital exemptions, use of private providers, and complex treatment patterns meant state‐provided protection had limitations. The significant non‐use of care shows the need for other measures such as more outreach services and more exemptions in rural areas. The findings also imply that fee removal anywhere must be accompanied by wider measures to ensure improved access.
Influences of herbicides, uprooting and use as cut flowers on sexual reproduction of Solidago canadensis
Authors: GUO S L , JIANG H W , FANG F , CHEN G Q 
Published: February 2009

Summary Solidago canadensis is a noxious invasive species in China. We examined the influences of herbicides on pollen germination and pollen tube growth and the effects of cutting flowers and herbicides on seed production and quality. We also determined the seed production and resource allocation to different organs of S. canadensis after uprooting the plants during their reproductive periods. The main results were as follows: (i) 49% pollen of S. canadensis was able to germinate on an appropriate medium; (ii) compared with paraquat, ethephon and 2,4‐D, glyphosate had an ideal inhibitory effect on pollen germination and the formation of seeds of S. canadensis; (3) cut flowering branches, when placed in water or nutrient solution, were still able to produce viable seeds; (4) resources were allocated more to the inflorescences to facilitate seed maturation after plants were uprooted at the flowering stage. Uprooted flower branches were still able to produce viable seeds, especially those in full flower. Therefore, in order to reduce the seed production of S. canadensis and spread of the species we suggest: (i) apply glyphosate at the flower bud stage, (ii) completely destroy uprooted plants at flowering stages and (iii) avoid using the flowering branches as ornamental materials.