bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescence‐based experimental model to evaluate the concomitant effect of drugs on the tumour microenvironment and cancer cells
Authors: Ramasamy Karthik , Khatun Hazera , Macpherson Lee , Caley Mathew P. , Sturge Justin , Mufti Ghulam J. , Schey Stephen A. , Calle Yolanda
Published: March 2012

The response of the tumour microenvironment to anti‐cancer drugs can influence treatment efficacy. Current drug‐screening methodologies fail to distinguish and quantify simultaneously the concomitant effect of drugs on the tumour stroma and cancer cells. To overcome this limitation we have developed a fluorescence‐based experimental model that employs mCherry‐labelled stromal cells (e.g. bone marrow fibroblastic stromal cells) co‐cultured in direct contact with enhanced green fluorescent protein‐labelled tumour cell lines for accurate assessment of proliferation and viability in both cell compartments and adhesion of tumour cells. Additionally, we used fluorescence‐based image analysis to determine morphological changes that correlate with cell function (e.g. morphology of the actin cytoskeleton and nuclearity of osteoclasts to predict their bone resorption activity). Using this platform we have revealed that dexamethasone induces HS5 fibroblast proliferation and contact with multiple myeloma cells via a process involving Src/c‐Abl kinases. Osteoclasts also inhibited dexamethasone‐induced apoptosis in myeloma cells while retaining their normal morphology and functionality in bone resorption. Myeloma resistance to dexamethasone mediated by HS5 cells and osteoclasts was reversed by treatment with the Src/c‐Abl inhibitor dasatinib but not with bortezomib. This new experimental platform provides a more precise screening of new therapeutics for improved efficacy of tumour cell killing within the bone marrow microenvironment.
Ex vivo expansion of cord blood progenitors impairs their short‐term and long‐term repopulating activity associated with transcriptional dysregulation of signalling networks
Authors: Holmes T. , Yan F. , Ko K.‐H. , Nordon R. , Song E. , O'Brien T. A. , Dolnikov A.
Published: March 2012

Objectives

Cord blood (CB) has been established to be an alternative source of haematopoietic stem/progenitor cells (HPC) for transplantation. The number of HPC per CB unit is limited, which results in engraftment delay. Ex vivo expansion of HPC improvement must overcome this.

Materials and methods

Flow cytometry was used to extensively phenotype HPC pre‐ and post‐expansion and CFDA‐SE staining was used to track cell divisions. The NSG mouse model was employed in transplantation studies to determine long and short term repopulation in human cells. Gene array analysis was used to evaluate signalling pathways regulated following ex vivo expansion of HPC.

Results

expansion of CD34+ HPC impaired their regenerative function. In this xenograft transplantation model we showed that repopulating activity of CB cells declined following expansion. Expanded HPC had delayed engraftment at early and late stages post‐transplant. High resolution division tracking revealed that the cultured HPC had reduced expansion and self‐renewal probability and increased differentiation rate compared to non‐expanded cells. Gene expression analysis exposed significant modulation of a complex network of genes and pathways that normally maintain HPC proliferation and limit their differentiation.

Conclusions

The decline in short‐term engraftment is consistent with the loss of rapid SCID repopulating ability r(SRA) by expanded CD34+CD38+ cells recently reported (1). Our data raise concerns for future clinical applications of expanded HPC alone in transplantation.
Acquired haemophilia A. First line treatment with calcineurin inhibitors and steroid pulses: a 10‐year follow‐up study
Authors: PARDOS‐GEA J. , ALTISENT C. , PARRA R. , VILARDELL‐TARRÈS M. , ORDI‐ROS J.
Published: March 2012

Summary.  Acquired haemophilia A (AH) is defined as the presence of autoantibodies or inhibitors against factor VIII (FVIII) with a clinical bleeding onset that can be life‐threatening. Immunosuppressant therapy must be initiated rapidly to eradicate the inhibitor. Current treatments based on steroids plus cyclophosphamide or rituximab are quite effective, but with significant side‐effects. Based on previous described AH cases treated with cyclosporine, with a good side‐effect profile, we aimed at assessing prospectively a first‐line calcineurin inhibitor based immunosuppressive therapy. We included a total of 11 patients affected with AH. Once diagnosed, pulse steroids and calcineurin inhibitors were started. Time to achieve sustained response (SR), defined as testing negative for inhibitor and with stable FVIII level >50%, immunosuppressant side‐effects, and relapse of AH were evaluated. Eight patients received cyclosporine and three patients received tacrolimus. SR was achieved in 10 of 11 patients (90.9%) in a median time of 3 weeks (range 2–8 weeks), and none of them relapsed during a median follow‐up time of 14 months (range 4–120). One major side‐effect appeared (posterior encephalopathy) that forced to discontinue cyclosporine. Overall 5‐year survival rate was 54.5%, with a total of five patients dying during the follow‐up (mortality rate of 45.5%). These five patients had achieved SR and died because of complications of basal morbidities and/or senescence, not related to AH (bleeding) or to immunosuppressant’s (infection) side‐effects. Combination therapy of calcineurin inhibitors and pulse steroids seems clinically effective as a first‐line treatment of AH.
Predictive‐focus illumination for reducing photodamage in live‐cell microscopy
Authors: SCHILLING Z. , FRANK E. , MAGIDSON V. , WASON J. , LONČAREK J. , BOYER K. , WEN J. , KHODJAKOV A.
Published: March 2012

Due to photobleaching and phototoxicity induced by high‐intensity excitation light, the number of fluorescence images that can be obtained in live cells is always limited. This limitation becomes particularly prominent in multidimensional recordings when multiple Z‐planes are captured at every time point. Here we present a simple technique, termed predictive‐focus illumination (PFI), which helps to minimize cells’ exposure to light by decreasing the number of Z‐planes that need to be captured in live‐cell 3D time‐lapse recordings. PFI utilizes computer tracking to predict positions of objects of interest (OOIs) and restricts image acquisition to small dynamic Z‐regions centred on each OOI. Importantly, PFI does not require hardware modifications and it can be easily implemented on standard wide‐field and spinning‐disc confocal microscopes.
Automatic cell counting in vivo in the larval nervous system of Drosophila
Authors: FORERO M.G. , KATO K. , HIDALGO A.
Published: March 2012

Identification and counting of cells is necessary to test biological hypotheses, for instance of nervous system formation, disease, degeneration, injury and regeneration, but manual counting is time consuming, tedious, and subject to bias. The fruit fly Drosophila is a widely used model organism to analyse gene function, and most research is carried out in the intact animal or in whole organs, rather than in cell culture. Inferences on gene function require that cell counts are known from these sample types. Image processing and pattern recognition techniques are appropriate tools to automate cell counting. However, counting cells in Drosophila is a complex task: variations in immunohistochemical markers and developmental stages result in images of very different properties, rendering it challenging to identify true cells. Here, we present a technique for counting automatically larval glial cells in three dimensions, from confocal microscopy serial optical sections. Local outlier thresholding and domes are combined to find the cells. Shape descriptors extracted from a data set are used to characterize cells and avoid oversegmentation. Morphological operators are employed to divide cells that could otherwise be missed. The method is accurate and very fast, and treats all samples equally and objectively, rendering all data comparable across specimens. Our method is also applicable to identify cells labelled with other nuclear markers and in sections of mouse tissues.
Historical distribution, habitat requirements and feeding ecology of the genus Equus (Perissodactyla)
Authors: Schulz Ellen , Kaiser Thomas M.
Published: March 2012

Dietary traits of nine extant Equus species (E. africanus, E. ferus, E. grevyi, E. hartmannae, E. hemionus, E. khur, E. kiang, E. quagga and E. zebra) were reconstructed and ranked in a continuum reflecting the relative proportions of abrasion and attrition.

In order to match them automatically with climatic data, localities were referenced within a 2° worldwide grid system using geographical information system software. The mesowear score was used as a proxy variable to test the covariance of diet with mean annual precipitation, evapotranspiration, mean annual climatic water balance and mean annual temperature.

Seven of the nine equid species presented mesowear signatures indicating a grass‐dominated diet, and we found interspecific as well as intraspecific variability. Non‐gramineous food components shifted the equilibrium towards the attrition‐dominated end in E. africanus and E. khur, indicating an intermediate diet. Especially in E. zebra, additional sources of exogenous abrasives (grit and soil) might increase dietary abrasiveness. In E. quagga, dietary flexibility and the capability to cope with increased abrasiveness are considered keystone factors allowing its large geographical range.

The broad, species‐specific range of climate parameters associated with the habitats was used to define the thresholds of the species' feeding niches. Our data suggest that climate as represented by the variables we used does not, in the first instance, relate to the tooth wear signature of equids.

We thus conclude that the tooth wear signature is more specific to the feeding strategy and should be regarded a dietary trait rather than an immediate imprint of climate. However, tooth wear can be used to infer local dietary traits and might therefore become an important tool in conservation management.
Plants and tortoises: mutations in the Arabidopsis jasmonate pathway increase feeding in a vertebrate herbivore
Authors: MAFLI ALIA , GOUDET JÉRÔME , FARMER EDWARD E.
Published: March 2012

Photosynthetic tissues, the major food source of many invertebrates and vertebrates, are well defended. Many defence traits in leaves are controlled via the jasmonate signalling pathway in which jasmonate acts as a hormone by binding to a receptor to activate responses that lead to increased resistance to invertebrate folivores. We predicted that mutations in jasmonate synthesis might also increase the vulnerability of leaves to vertebrate folivores and tested this hypothesis using the Eastern Hermann’s tortoise (Eurotestudo boettgeri) and an Arabidopsis thaliana (Brassicaceae) allene oxide synthase (aos) mutant unable to synthesize jasmonate. Tortoises preferred the aos mutant over the wild type (WT). Based on these results, we then investigated the effect of mutating jasmonate perception using a segregating population of the recessive A. thaliana jasmonate receptor mutant coronatine insensitive1‐1 (coi1‐1). Genotyping of these plants after tortoise feeding revealed that the homozygous coi1‐1 receptor mutant was consumed more readily than the heterozygous mutant or the WT. Therefore, the plant’s ability to synthesize or perceive jasmonate reduces feeding by a vertebrate herbivore. We also tested whether or not tortoise feeding behaviour was influenced by glucosinolates, the principal defence chemicals in Arabidopsis leaves with known roles in defence against many generalist insects. However, in contrast to what has been observed with such insects, leaves in which the levels of these compounds were reduced genetically were consumed at a similar rate to those of the WT.
Perceived service quality, perceived value, overall satisfaction and happiness of outlook for long‐term care institution residents
Authors: Lin Jesun , Hsiao Chih‐Tung , Glen Robert , Pai Jar‐Yuan , Zeng Sin‐Huei
Published: March 2012

Objective  To investigate the psychometric properties and relationships of perceived service quality, perceived value and overall satisfaction for residents with respect to their long‐term care institutions.

Design  The five‐point Likert scale questionnaire administered through facetoface interviews.

Setting  Fourteen long‐term care institutions located in central and southern Taiwan stratified according to services and accommodation population.

Participants  One hundred and eighty long‐term institutional care residents.

Main outcome measures  Perceived service quality (the SERVPERF model), perceived value and overall satisfaction (models based on the literature on perceived value and satisfaction).

Results  Student’s t‐test on institutional location shows a significant difference between overall satisfaction for central and southern institution long‐term care recipients. The correlation test revealed that the higher a resident’s level of education, the higher the scores for perceived value. The factor loading results of confirmation factor analysis show acceptable levels of reliability and index‐of‐model fits for perceived service, perceived value and overall satisfaction. In addition, the results suggest that an additional construct, a positive attitude (happiness of outlook) towards long‐term care institutions, is also an important factor in residents’ overall satisfaction.

Conclusion  The primary goal of long‐term institutional care policy in Taiwan, as in other countries, is to provide residents with practical, cost‐effective but high‐quality care. On the basis of the results of in‐depth interviews with long‐term institutional care residents, this study suggests long‐term care institutions arrange more family visit days to increase the accessibility and interaction of family and residents and thereby increase the happiness of outlook of the residents.
Fatal Burkholderia gladioli infection misidentified as Empedobacter brevis in a lung transplant recipient with cystic fibrosis
Authors: Brizendine K.D. , Baddley J.W. , Pappas P.G. , Leon K.J. , Rodriguez J.M.
Published: March 2012

Data describing the risk of lung transplantation (LT), clinical features, and outcomes of patients with cystic fibrosis (CF) infected with Burkholderia gladioli are limited. Herein, we report a case of disseminated B. gladioli infection characterized by bacteremia, necrotizing pneumonia, lung abscess, and empyema in a lung transplant recipient with CF, highlight the importance of accurate microbiological identification, and review published outcomes of LT in CF patients infected with B. gladioli, which include cases of pneumonia, tracheobronchitis, bacteremia, and abscesses, and demonstrate an all‐cause 1‐year mortality of approximately 23%, often after combined medical and surgical treatment.
Limitation of repeated radiofrequency ablation in hepatocellular carcinoma: Proposal of a three (times) ×  3 (years) index
Authors: Yokoyama Keiji , Anan Akira , Iwata Kaoru , Nishizawa Shinya , Morihara Daisuke , Ueda Shu‐ichi , Sakurai Kunitoshi , Iwashita Hideyuki , Hirano Genryu , Sakamoto Masaharu , Takeyama Yasuaki , Irie Makoto , Shakado Satoshi , Sohda Tetsuro , Sakisaka Shotaro
Published: March 2012

Background and Aim:  Percutaneous radiofrequency ablation (RFA) has been shown to be a highly effective treatment for hepatocellular carcinoma (HCC). We investigated the controllability of HCC and explored the algorithm of therapeutic strategy for HCC in patients who met the RFA criteria.

Methods:  We enrolled 472 patients with HCC who met the RFA criteria (≤ 3 nodules, ≤ 3 cm) and underwent RFA for initial therapy. Patients who underwent repeated RFA were evaluated retrospectively when HCC exceeded the RFA criteria, or the functional hepatic reserve progressed to Child–Pugh grade C.

Results:  Overall survival rates were: 1 year, 96%; 3 years, 79%; and 5 years, 56%. In 5 years, 14% of patients progressed to Child–Pugh grade C. Meanwhile, 47% of patients exceeded the RFA criteria. Annually, 8% of patients deviated from the RFA criteria. The percentage of patients who were able to receive RFA significantly decreased at the fourth session compared with up to the third session. The survival rates decreased at the rate of 7% annually until the third year after the initial RFA. Afterwards, it shifted to a decrease at the rate of 12% annually. In a multivariate analysis, the presence of hepatitis C virus infection and the existence of a single tumor were identified as significant independent factors contributing to probabilities exceeding the RFA criteria.

Conclusions:  HCC was controlled by RFA up to three RFA treatments and 3 years from the initial therapy. On this basis, we propose a “three (times) × 3 (years) index” for considering a shift from RFA to other treatment modalities.
Identification of functionally active aerobic methanotrophs in sediments from an arctic lake using stable isotope probing
Authors: He Ruo , Wooller Matthew J. , Pohlman John W. , Catranis Catharine , Quensen John , Tiedje James M. , Leigh Mary Beth
Published: March 2012

Arctic lakes are a significant source of the greenhouse gas methane (CH4), but the role that methane oxidizing bacteria (methanotrophs) play in limiting the overall CH4 flux is poorly understood. Here, we used stable isotope probing (SIP) techniques to identify the metabolically active aerobic methanotrophs in upper sediments (0–1 cm) from an arctic lake in northern Alaska sampled during ice‐free summer conditions. The highest CH4 oxidation potential was observed in the upper sediment (0–1 cm depth) with 1.59 µmol g wet weight−1 day−1 compared with the deeper sediment samples (1–3 cm, 3–5 cm and 5–10 cm), which exhibited CH4 oxidation potentials below 0.4 µmol g wet weight−1 day−1. Both type I and type II methanotrophs were directly detected in the upper sediment total communities using targeted primer sets based on 16S rRNA genes. Sequencing of 16S rRNA genes and functional genes (pmoA and mxaF) in the 13C‐DNA from the upper sediment indicated that type I methanotrophs, mainly Methylobacter, Methylosoma, Methylomonas and Methylovulum miyakonense, dominated the assimilation of CH4. Methylotrophs, including the genera Methylophilus and/or Methylotenera, were also abundant in the 13C‐DNA. Our results show that a diverse microbial consortium acquired carbon from CH4 in the sediments of this arctic lake.
Environmental conditions that influence toxin biosynthesis in cyanobacteria
Authors: Neilan Brett A. , Pearson Leanne A. , Muenchhoff Julia , Moffitt Michelle C. , Dittmann Elke
Published: March 2012

Over the past 15 years, the genetic basis for production of many cyanobacterial bioactive compounds has been described. This knowledge has enabled investigations into the environmental factors that regulate the production of these toxins at the molecular level. Such molecular or systems level studies are also likely to reveal the physiological role of the toxin and contribute to effective water resource management. This review focuses on the environmental regulation of some of the most relevant cyanotoxins, namely the microcystins, nodularin, cylindrospermopsin, saxitoxins, anatoxins and jamaicamides.
Alpha and Beta Traits and Egoistic and Moralistic Self‐Enhancement: A Point of Convergence Between Two Research Traditions
Authors: Vecchione Michele , Alessandri Guido
Published: March 2012

Objective

The current study investigated the relationship of egoistic and moralistic self‐enhancement with Alpha and Beta, the two higher‐order factors of personality encompassing the Big Five.

Method

Four hundred sixteen Italian adults (59% females, mean age = 41.13) completed self‐report measures of the Big Five and of egoistic and moralistic self‐enhancement. They were also rated by acquaintances on the two self‐enhancement measures. A cross‐observer design within the framework of structural equation modeling was used to disentangle the variance shared by the constructs that is due to (a) substantive personality characteristics (i.e., the variance of egoistic and moralistic self‐enhancement common to different informants), (b) response bias (i.e., the tendency to exaggerate agentic and communal qualities), and (c) halo effect (i.e., the common factor underlying all self‐report measures).

Results

Findings revealed significant correlations between Alpha and Beta and the substantive parts of egoistic and moralistic dimensions. Beta was primarily related to egoistic self‐enhancement, whereas alpha was mostly related to moralistic self‐enhancement. Nevertheless, a substantial portion of variance in Alpha and Beta was explained by response bias and halo effect.

Conclusions

Substance, bias, and method variance all represent important sources of covariation among the Big Five.
Genetic Influences on Psychological Well‐Being: A Nationally Representative Twin Study
Authors: Archontaki Despina , Lewis Gary J. , Bates Timothy C.
Published: March 2012

Objective

Psychological well‐being, or eudaimonia, features strongly in theories of human development and thriving. However, the factors of eudaimonia are debated, and their genetic architecture has not been studied in detail.

Method

A classical twin design was used to decompose behavioral variance into genetic and environmental components implemented in a multigroup, multivariate structural equation modeling framework. Subjects were 837 pairs of adult U.S. twins from the nationally representative MIDUS II sample. Psychological well‐being was measured using the 42‐item Ryff Psychological Well‐Being Scale, which assesses autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self‐acceptance.

Results

Substantial genetic influences were observed on all components of well‐being. Attempts to model these six factors as reflecting a single common psychological mechanism gave a poor fit to the data. The best‐fitting model supported the existence of five distinct genetic effects. Effects of shared environment were weak and nonsignificant. Unique environmental effects for all measures were mostly trait specific.

Conclusions

These results indicate that psychological well‐being is underpinned by a general genetic factor influencing self‐control, and four underlying biological mechanisms enabling the psychological capabilities of purpose, agency, growth, and positive social relations.
Ecophylogenetics: advances and perspectives
Authors: Mouquet Nicolas , Devictor Vincent , Meynard Christine N. , Munoz Francois , Bersier Louis‐Félix , Chave Jérôme , Couteron Pierre , Dalecky Ambroise , Fontaine Colin , Gravel Dominique , Hardy Olivier J. , Jabot Franck , Lavergne Sébastien , Leibold Mathew , Mouillot David , Münkemüller Tamara , Pavoine Sandrine , Prinzing Andreas , Rodrigues Ana S.L. , Rohr Rudolf P. , Thébault Elisa , Thuiller Wilfried
Published: March 2012

Ecophylogenetics can be viewed as an emerging fusion of ecology, biogeography and macroevolution. This new and fast‐growing field is promoting the incorporation of evolution and historical contingencies into the ecological research agenda through the widespread use of phylogenetic data. Including phylogeny into ecological thinking represents an opportunity for biologists from different fields to collaborate and has provided promising avenues of research in both theoretical and empirical ecology, towards a better understanding of the assembly of communities, the functioning of ecosystems and their responses to environmental changes. The time is ripe to assess critically the extent to which the integration of phylogeny into these different fields of ecology has delivered on its promise. Here we review how phylogenetic information has been used to identify better the key components of species interactions with their biotic and abiotic environments, to determine the relationships between diversity and ecosystem functioning and ultimately to establish good management practices to protect overall biodiversity in the face of global change. We evaluate the relevance of information provided by phylogenies to ecologists, highlighting current potential weaknesses and needs for future developments. We suggest that despite the strong progress that has been made, a consistent unified framework is still missing to link local ecological dynamics to macroevolution. This is a necessary step in order to interpret observed phylogenetic patterns in a wider ecological context. Beyond the fundamental question of how evolutionary history contributes to shape communities, ecophylogenetics will help ecology to become a better integrative and predictive science.
Reciprocal transplants demonstrate strong adaptive differentiation of the model organism Arabidopsis thaliana in its native range
Authors: Ågren Jon , Schemske Douglas W.
Published: March 2012

See also the Commentary by Lowry
Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and soluble endoglin in the prediction of pre‐eclampsia: a systematic review and meta‐analysis
Authors: Kleinrouweler CE , Wiegerinck MMJ , Ris‐Stalpers C , Bossuyt PMM , van der Post JAM , von Dadelszen P , Mol BWJ , Pajkrt E ,   for the EBM CONNECT Collaboration
Published: March 2012

Please cite this paper as: Kleinrouweler C, Wiegerinck M, Ris‐Stalpers C, Bossuyt P, van der Post J, von Dadelszen P, Mol B, Pajkrt E, for the EBM CONNECT Collaboration. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and soluble endoglin in the prediction of pre‐eclampsia: a systematic review and meta‐analysis. BJOG 2012;119:778–787.

Background  Biomarkers have been proposed for identification of women at increased risk of developing pre‐eclampsia.

Objectives  To investigate the capacity of circulating placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble fms‐like tyrosine kinase‐1 (sFLT1) and soluble endoglin (sENG) to predict pre‐eclampsia.

Search strategy  Medline and Embase through October 2010 and reference lists of reviews, without constraints.

Selection criteria  We included original publications on testing of PlGF, VEGF, sFLT1 and sENG in serum or plasma of pregnant women at <30 weeks of gestation and before clinical onset of pre‐eclampsia.

Data collection and analysis  Two reviewers independently identified eligible studies, extracted descriptive and test accuracy data and assessed methodological quality. Summary estimates of discriminatory performance were obtained.

Main results  We included 34 studies. Concentrations of PlGF (27 studies) and VEGF (three studies) were lower in women who developed pre‐eclampsia: standardised mean differences (SMD) −0.56 (95% CI −0.77 to −0.35) and −1.25 (95% CI −2.73 to 0.23). Concentrations of sFLT1 (19 studies) and sENG (ten studies) were higher: SMD 0.48 (95% CI 0.21–0.75) and SMD 0.54 (95% CI 0.24–0.84). The summary diagnostic odds ratios were: PlGF 9.0 (95% CI 5.6–14.5), sFLT1 6.6 (95% CI 3.1–13.7), sENG 4.2 (95% CI 2.4–7.2), which correspond to sensitivities of 32%, 26% and 18%, respectively, for a 5% false‐positive rate.

Author’s conclusions  PlGF, sFLT1 and sENG showed modest but significantly different concentrations before 30 weeks of gestation in women who developed pre‐eclampsia. Test accuracies of all four markers, however, are too poor for accurate prediction of pre‐eclampsia in clinical practice.
The significance of Mg in prebiotic geochemistry
Authors: HOLM N. G.
Published: March 2012

Magnesium plays a special role in biochemistry because of its ability to coordinate six oxygen atoms efficiently in its first coordination shell. Such oxygen atoms may be part of one or two charged oxyanions, which means that Mg2+ can, for instance, tie together two different phosphate groups that are located at distance from each other in a macromolecule, and in this way be responsible for the folding of molecules like RNA. This property of Mg2+ also helps the stabilization of diphosphate and triphosphate groups of nucleotides, as well as promoting the condensation of orthophosphate to oligophosphates, like pyrophosphate and trimetaphosphate. Borates, on the other hand, are known to promote the formation of nucleobases and carbohydrates, ribose in particular, which is yet another constituent of nucleotides. The oldest borate minerals that we find on Earth today are magnesium borates. Dissolved borate stabilizes pentose sugars by forming complexes with cis‐hydroxyl groups. In the furanose form of ribose, the preferential binding occurs to the 2 and 3 carbon, leaving the 5 carbon free for phosphorylation. The central role of Mg2+ in the function of ribozymes and its ‘archaic’ position in ribosomes, and the fact that magnesium generally has coordination properties different from other cations, suggests that the inorganic chemistry of magnesium had a key position in the first chemical processes leading to the origin and early evolution of life.
Buprenorphine exposure in infants of opioid‐dependent mothers at birth
Authors: Bartu Anne E. , Ilett Kenneth F. , Hackett L. Peter , Doherty Dorota A. , Hamilton Dale
Published: March 2012

Background

Buprenorphine, a partial opioid agonist used in treating opioid dependence, is not approved in Australia for use in pregnancy. Nevertheless, many pregnant women choose to remain on the drug.

Aim

To investigate cord/maternal transfer ratios for buprenorphine and norbuprenorphine in women at delivery.

Methods

Maternal and cord serum samples were collected from 10 maternal‐infant pairs at delivery. Drug concentrations were measured by liquid chromatography‐tandem mass spectrometry. Maternal and infant demographic information was collected. Linear regression was used to assess the relationship between maternal and cord measurements.

Results

Median (interquartile range) maternal age was 27 (23.8–32) years, with 90% of the women on buprenorphine before pregnancy. Median infant birthweight was 3148 (3088–3545) g and 60% of infants had neonatal abstinence requiring admission to a neonatal intensive care unit for a median of 8.5 (2.5–16.3) days. Median maternal buprenorphine daily dose was 8.5 mg (range 1–28 mg). Mean (95% confidence interval) cord serum concentrations of buprenorphine and norbuprenorphine were 0.4 (0.3–0.5) μg/L and 1.2 (0.9–1.4) μg/L, respectively. Mean maternal concentrations of buprenorphine and norbuprenorphine were 1.0 (0.6–1.4) μg/L and 1.2 (0.9–1.4) μg/L, respectively. Mean cord/maternal ratios were 0.43 (0.36–0.5) for buprenorphine and 0.53 (0.43–0.63) for norbuprenorphine. Maternal buprenorphine and norbuprenorphine concentrations and ratio of buprenorphine/norbuprenorphine explained 85.7, 69.6 and 94.4%, respectively, of variation in the corresponding cord concentrations.

Conclusion

Usual therapeutic doses of buprenorphine administered to pregnant women resulted in low concentrations of buprenorphine and norbuprenorphine in maternal serum and a low transfer to the fetal circulation (cord plasma) at birth.
Gemifloxacin Can Partially Overcome Quinolone Resistance of H. pylori with gyrA Mutation in Taiwan
Authors: Chang Wei‐Lun , Kao Cheng‐Yen , Wu Chung‐Tai , Huang Ay‐Huey , Wu Jiunn‐Jong , Yang Hsiao‐Bai , Cheng Hsiu‐Chi , Sheu Bor‐Shyang
Published: March 2012

Backgrounds:  The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori.

Materials and Methods:  Forty‐four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin‐sensitive controls were tested for gemifloxacin sensitivity by E‐test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) >1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance.

Results:  All levofloxacin‐sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5‐time lower in MIC levels against levofloxacin‐resistant isolates. Nearly all levofloxacin‐resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high‐level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin‐sensitive and levofloxacin‐resistant. The gemifloxacin‐resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05).

Conclusion:  Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.
Length of Thymidine Homopolymeric Repeats Modulates Promoter Activity of sabA in Helicobacter pylori
Authors: Kao Cheng‐Yen , Sheu Shew‐Meei , Sheu Bor‐Shyang , Wu Jiunn‐Jong
Published: March 2012

Background:  Helicobacter pylori uses SabA to interact with sialyl‐Lewis x on the gastric mucosal surface to establish persistent colonization. The number of CT repeats in sabA is variable and thus influences SabA translation, but the expression of SabA determined by Western blotting does not fully match with a CT sequence‐based prediction. Furthermore, a homopolymeric thymidine (polyT) tract located upstream of sabA has been observed, but its role in regulating sabA expression is still unknown.

Methods:  The transcriptional start site (TSS) of sabA in strains J99 and Hp258 was determined by 5′ RACE. One hundred and fifteen clinical isolates were sequenced to analyze the distribution of the polyT tract length and promoter sequence. Finally, RT‐PCR and an E. coli‐lux reporter system were used to determine the sabA promoter activity with different lengths of the polyT tract.

Results:  The TSS of sabA was located at 66 or 64 bp upstream of the translational start codon in J99 and Hp258, respectively. The polyT tract close to the −35 element varied from T10 to T28 in 115 clinical isolates, and 70% of the isolates contained a stretch of 14–19 Ts. The sabA gene displayed slipped strand mispairing (SSM) of the polyT tract, generating varying genotypes in J99 (16–18 Ts) and Hp258 (14–15 Ts). Furthermore, J99 with lengths of T16 and T30, had higher sabA promoter activity than the common length of T18.

Conclusion:  Our findings indicate that the sabA promoter region modulates its transcriptional activity through a variable polyT tract, and SSM generates mixed genotypes in the population.
Comprehensive Investigation of Areae Gastricae Pattern in Gastric Corpus using Magnifying Narrow Band Imaging Endoscopy in Patients with Chronic Atrophic Fundic Gastritis
Authors: Kanzaki Hiromitsu , Uedo Noriya , Ishihara Ryu , Nagai Kengo , Matsui Fumi , Ohta Takashi , Hanafusa Masao , Hanaoka Noboru , Takeuchi Yoji , Higashino Koji , Iishi Hiroyasu , Tomita Yasuhiko , Tatsuta Masaharu , Yamamoto Kazuhide
Published: March 2012

Background:  Barium radiographic studies have suggested the importance of evaluating areae gastricae pattern for the diagnosis of gastritis. Significance of endoscopic appearance of areae gastricae in the diagnosis of chronic atrophic fundic gastritis (CAFG) was investigated by image‐enhanced endoscopy.

Materials and Methods:  Endoscopic images of the corpus lesser curvature were studied in 50 patients with CAFG. Extent of CAFG was evaluated with autofluorescence imaging endoscopy. The areae gastricae pattern was evaluated with 0.2% indigo carmine chromoendoscopy. Micro‐mucosal structure was examined with magnifying chromoendoscopy and narrow band imaging.

Results:  In patients with small extent of CAFG, polygonal areae gastricae separated by a narrow intervening part of areae gastricae was observed, whereas in patients with wide extent of CAFG, the size of the areae gastricae decreased and the width of the intervening part of areae gastricae increased (p < 0.001). Most areae gastricae showed a foveola‐type micro‐mucosal structure (82.7%), while intervening part of areae gastricae had a groove‐type structure (98.0%, p < 0.001). Groove‐type mucosa had a higher grade of atrophy (p < 0.001) and intestinal metaplasia (p < 0.001) compared with foveola type.

Conclusions:  As extent of CAFG widened, multifocal groove‐type mucosa that had high‐grade atrophy and intestinal metaplasia developed among areae gastricae and increased along the intervening part of areae gastricae. Our observations facilitate our understanding of the development and progression of CAFG.
Comparison of Lafutidine and Rabeprazole in 7‐day Second‐line Amoxicillin‐ and Metronidazole‐Containing Triple Therapy for Helicobacter pylori: A Pilot Study
Authors: Kudo Takahiko , Fujinami Haruka , Ando Takayuki , Nishikawa Jun , Ogawa Kohei , Hosokawa Ayumu , Orihara Tadahiro , Murakami Jun , Takahara Terumi , Sugiyama Toshiro
Published: March 2012

Background:  Lafutidine is an H2‐receptor antagonist with gastroprotective action through capsaicin‐sensitive afferent neurons and relatively inexpensive compare to proton‐pump inhibitors (PPIs). A 7‐day course of PPIs–amoxicillin–metronidazole is recommended as standard second‐line Helicobacter pylori therapy and is covered by national health insurance in Japan. The aim of this study was to determine the efficacy and safety of second‐line eradication using the H2‐receptor antagonist lafutidine as a substitute for a PPI.

Materials and Methods:  Fifty‐two patients who failed in first‐line eradication using PPI–amoxicillin–clarithromycin were randomly assigned to a 7‐day course of rabeprazole at 10 mg b.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (RPZ‐AM) or a 7‐day course of lafutidine at 10 mg t.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (LFT‐AM) as second‐line therapy. Eradication was assessed by the 13C urea breath test. A drug susceptibility test was performed before the second‐line therapy.

Results:  Prior to second‐line H. pylori eradication, the rate of resistance to clarithromycin was 86.5% and the rate of resistance to metronidazole was 3.8%. The eradication rates for both LFT‐AM and RPZ‐AM groups were 96% (95%CI = 88.6–100%). There were no severe adverse events in either group.

Conclusions:  Lafutidine plus metronidazole–amoxicillin as second‐line therapy provided a high eradication rate and safe treatment similar to a PPI‐based regimen. Lafutidine‐based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication.
A Systematic Method to Document Population‐Level Nursing Interventions in an Electronic Health System
Authors: Baisch Mary Jo
Published: March 2012

Many public health electronic health systems lack the specificity to distinguish between individual‐ and population‐based levels of care provided by public health nurses. Data that describe the broad scope of the everyday practice of public health nurses are critical to providing evidence of their effectiveness in promoting community health, which may not be fully appreciated in an arena of scarce resources. This article describes a method to document population‐based nursing practice by adding population‐based interventions to the nursing taxonomy underlying an electronic health information system. These interventions, derived from the Intervention Wheel, were incorporated into the Omaha System taxonomy, the conceptual framework for the Automated Community Health Information System (ACHIS), which is a longstanding data system used to capture nursing practice in community nursing centers. This article includes a description of the development and testing of the system's ability to capture the practice of the district public health nurse model. This method of adapting an existing data system to capture population‐based interventions could be replicated by public health administrators interested in better evaluating the processes and outcomes of public health nursing and other public health professionals.
Computational analysis of intersubject variability and thrombin generation in dilutional coagulopathy
Authors: Mitrophanov Alexander Y. , Rosendaal Frits R. , Reifman Jaques
Published: March 2012

BACKGROUND: Blood dilution is a frequent complication of massive transfusion during trauma and surgery. This article investigates the quantitative effects of blood plasma dilution on thrombin generation in the context of intersubject variability.

STUDY DESIGN AND METHODS: A thoroughly validated computational model was used to simulate thrombin generation curves for 472 healthy subjects in the Leiden Thrombophilia Study. Individual thrombin curves were calculated for undiluted blood and for different dilution scenarios. For every such curve, five standard quantitative parameters of thrombin generation were calculated and analyzed.

RESULTS: Thrombin generation parameters in diluted blood plasma displayed significant intersubject variability (with a coefficient of variation up to approx. 28%). Nevertheless, dilutional effects in the majority (or all) of the subjects in the study group were characterized by persistent patterns. In particular, the largest dilution‐induced change typically occurred in the maximum slope (MS) of the thrombin curve, followed by a change in thrombin peak height (PH), whereas the smallest change often occurred in the area under the curve. The identified patterns demonstrated considerable robustness to variations in dilution scenario and tissue factor concentration.

CONCLUSION: Dilutional effects on thrombin generation in a human population can be predicted from trends identified for the “average” subject and then refined by performing an analysis of actual subjects in the study group. The MS and PH are dilution indicators that are both sensitive and reliable across a large subject group and could potentially be used as disease markers in the diagnosis of coagulopathic conditions.
The Effects of Personality Type on Choices Made in Strategic Decision Situations*
Authors: Stumpf Stephen A. , Dunbar Roger L.M.
Published: March 2012

Jung's personality‐theory typology is used as a framework for exploring the effects of cognitive style on the type and radicalness of choices made in strategic decision situations. Extending the work of Haley and Stumpf [23], it is proposed that individuals with different personality‐type preferences exhibit cognitive styles that are associated with specific biases in the pattern of choices they make. Through participation in an interactive behavioral simulation, 407 participants confronted over one hundred ill‐structured decision situations and proposed whatever actions they perceived appropriate. The results support the hypothesized relationships that individuals with different personality‐type preferences (i.e., sensing‐thinking, intuition‐thinking, sensing‐feeling, and intuition‐feeling) take patterns of actions that reflect specific biases (i.e., selective perception, positivity, social desirability, and reasoning‐by‐analogy, respectively). The implications of these findings for evaluating the likely effectiveness of strategic decisions and making senior‐level staffing decisions are discussed.
Virtual microscopy and digital pathology in training and education
Authors: Hamilton Peter W. , Wang Yinhai , McCullough Stephen J.
Published: March 2012

Traditionally, education and training in pathology has been delivered using textbooks, glass slides and conventional microscopy. Over the last two decades, the number of web‐based pathology resources has expanded dramatically with centralized pathological resources being delivered to many students simultaneously. Recently, whole slide imaging technology allows glass slides to be scanned and viewed on a computer screen via dedicated software. This technology is referred to as virtual microscopy and has created enormous opportunities in pathological training and education. Students are able to learn key histopathological skills, e.g. to identify areas of diagnostic relevance from an entire slide, via a web‐based computer environment. Students no longer need to be in the same room as the slides. New human–computer interfaces are also being developed using more natural touch technology to enhance the manipulation of digitized slides. Several major initiatives are also underway introducing online competency and diagnostic decision analysis using virtual microscopy and have important future roles in accreditation and recertification. Finally, researchers are investigating how pathological decision‐making is achieved using virtual microscopy and modern eye‐tracking devices. Virtual microscopy and digital pathology will continue to improve how pathology training and education is delivered.
Utility of whole slide imaging and virtual microscopy in prostate pathology
Authors: Camparo Philippe , Egevad Lars , Algaba Ferran , Berney Daniel M. , Boccon‐Gibod Liliane , Compérat Eva , Evans Andrew J. , Grobholz Rainer , Kristiansen Glen , Langner Cord , Lopez‐Beltran Antonio , Montironi Rodolfo , Oliveira Pedro , Vainer Ben , Varma Murali
Published: March 2012

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side‐by‐side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter‐observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z‐scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.