bluuebunny/crossref_metadata_2025 huggingface dataset:
Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein
Authors: Kulman John D. , Harris Jeff E. , Xie Ling , Davie Earl W.
Published: May 2007

Proline-rich Gla protein 2 (PRGP2) is one of four known vertebrate transmembrane γ-carboxyglutamic acid (Gla) proteins. Members of this protein family are broadly expressed in fetal and adult human tissues and share a common architecture consisting of a predicted propeptide and Gla domain, a single-pass transmembrane segment, and tandem Pro/Leu-Pro-Xaa-Tyr (PY) motifs near their C termini. Using a methodology developed for the regulated expression of enzymatically biotinylated proteins in mammalian cells, we demonstrate that PRGP2 undergoes γ-glutamyl carboxylation in a manner that is both dependent upon the presence of a proteolytically cleavable propeptide and sensitive to warfarin, a vitamin K antagonist that is widely used as an antithrombotic agent. When expressed at physiologically relevant levels, the majority of PRGP2 is present in the γ-glutamyl carboxylated, propeptide-cleaved (mature) form. We additionally demonstrate, by Western blotting and flow cytometry, that mature PRGP2 is predominantly located on the cell surface with the Gla domain exposed extracellularly. In a yeast two-hybrid screen that used the C-terminal cytoplasmic region of PRGP2 as bait, we identified the WW domain-containing transcriptional coactivator Yes-associated protein (YAP) as a binding partner for PRGP2. In GST pull-down experiments, both PRGP2 PY motifs and both YAP WW domains were essential for complex formation, as were residues proximal to the core sequence of the first PY motif. These findings suggest that PRGP2 may be involved in a signal transduction pathway, the impairment of which may be an unintended consequence of warfarin therapy.
Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKCα
Authors: Gaboreanu Ana-Maria , Hrstka Ronald , Xu Wenbo , Shy Michael , Kamholz John , Lilien Jack , Balsamo Janne
Published: May 2007

Point mutations in the cytoplasmic domain of myelin protein zero (P0; the major myelin protein in the peripheral nervous system) that alter a protein kinase Cα (PKCα) substrate motif (198HRSTK201) or alter serines 199 and/or 204 eliminate P0-mediated adhesion. Mutation in the PKCα substrate motif (R198S) also causes a form of inherited peripheral neuropathy (Charcot Marie Tooth disease [CMT] 1B), indicating that PKCα-mediated phosphorylation of P0 is important for myelination. We have now identified a 65-kD adaptor protein that links P0 with the receptor for activated C kinase 1 (RACK1). The interaction of p65 with P0 maps to residues 179–197 within the cytoplasmic tail of P0. Mutations or deletions that abolish p65 binding reduce P0 phosphorylation and adhesion, which can be rescued by the substitution of serines 199 and 204 with glutamic acid. A mutation in the p65-binding sequence G184R occurs in two families with CMT, and mutation of this residue results in the loss of both p65 binding and adhesion function.
Stra13 regulates satellite cell activation by antagonizing Notch signaling
Authors: Sun Hong , Li Li , Vercherat Cécile , Gulbagci Neriman Tuba , Acharjee Sujata , Li Jiali , Chung Teng-Kai , Thin Tin Htwe , Taneja Reshma
Published: May 2007

Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation.
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
Authors: Deaglio Silvia , Dwyer Karen M. , Gao Wenda , Friedman David , Usheva Anny , Erat Anna , Chen Jiang-Fan , Enjyoji Keiichii , Linden Joel , Oukka Mohamed , Kuchroo Vijay K. , Strom Terry B. , Robson Simon C.
Published: May 2007

The study of T regulatory cells (T reg cells) has been limited by the lack of specific surface markers and an inability to define mechanisms of suppression. We show that the expression of CD39/ENTPD1 in concert with CD73/ecto-5′-nucleotidase distinguishes CD4+/CD25+/Foxp3+ T reg cells from other T cells. These ectoenzymes generate pericellular adenosine from extracellular nucleotides. The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. Consequently, T reg cells from Cd39-null mice show impaired suppressive properties in vitro and fail to block allograft rejection in vivo. We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation.
Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program
Authors: Dhodapkar Kavita M. , Banerjee Devi , Connolly John , Kukreja Anjli , Matayeva Elyana , Veri Maria Concetta , Ravetch Jeffrey V. , Steinman Ralph M. , Dhodapkar Madhav V.
Published: May 2007

The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies, we have shown that selective antibody-mediated blockade of inhibitory FcγRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. We show that Fcγ receptor (FcγR)–mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation-associated chemokines, as well as type 1 interferon (IFN) response genes, including the activation of signal transducer and activator of transcription 1 (STAT1). FcγR-mediated STAT1 activation is rapid and requires activating FcγRs. However, this IFN response is observed without a detectable increase in the expression of type I IFNs themselves or the need to add exogenous IFNs. Induction of IFN response genes plays an important role in FcγR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcγR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcγRs may regulate IFN signaling in myeloid cells. Manipulation of FcγR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.
Developing the Deutsch–Hayden approach to quantum mechanics
Authors: Horsman Dominic , Vedral V
Published: May 2007

The formalism of Deutsch and Hayden is a useful tool for describing quantum mechanics explicitly as local and unitary, and therefore quantum information theory as concerning a ‘flow’ of information between systems. In this paper we show that these physical descriptions of flow are unique, and develop the approach further to include the measurement interaction and mixed states. We then give an analysis of entanglement swapping in this approach, showing that it does not in fact contain either nonlocal effects or any form of superluminal signalling.
Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo
Authors: Cheung Yuen-Nei , Maag David , Mitchell Sarah F. , Fekete Christie A. , Algire Mikkel A. , Takacs Julie E. , Shirokikh Nikolay , Pestova Tatyana , Lorsch Jon R. , Hinnebusch Alan G.
Published: May 2007

Selection of the AUG start codon is a key step in translation initiation requiring hydrolysis of GTP in the eIF2•GTP•Met-tRNAiMet ternary complex (TC) and subsequent Pi release from eIF2•GDP•Pi. It is thought that eIF1 prevents recognition of non-AUGs by promoting scanning and blocking Pi release at non-AUG codons. We show that Sui− mutations in Saccharomyces cerevisiae eIF1, which increase initiation at UUG codons, reduce interaction of eIF1 with 40S subunits in vitro and in vivo, and both defects are diminished in cells by overexpressing the mutant proteins. Remarkably, Sui− mutation ISQLG93–97ASQAA (abbreviated 93–97) accelerates eIF1 dissociation and Pi release from reconstituted preinitiation complexes (PICs), whereas a hyperaccuracy mutation in eIF1A (that suppresses Sui− mutations) decreases the eIF1 off-rate. These findings demonstrate that eIF1 dissociation is a critical step in start codon selection, which is modulated by eIF1A. We also describe Gcd− mutations in eIF1 that impair TC loading on 40S subunits or destabilize the multifactor complex containing eIF1, eIF3, eIF5, and TC, showing that eIF1 promotes PIC assembly in vivo beyond its important functions in AUG selection.
The Prp18 protein stabilizes the interaction of both exons with the U5 snRNA during the second step of pre-mRNA splicing
Authors: Crotti Luciana B. , Bačíková Dagmar , Horowitz David S.
Published: May 2007

Interaction of the ends of the exons with loop 1 of the U5 snRNA aligns the exons for ligation in the second step of pre-mRNA splicing. To study the effect of Prp18 on the exons’ interactions, we analyzed the splicing of pre-mRNAs with random sequences in the exon bases at the splice junctions. The exon mutations had large effects on splicing in yeast with a Prp18 protein lacking its most conserved region, but not in wild-type yeast. Analysis of splicing kinetics demonstrated that only the second step was affected in vivo and in vitro, showing that Prp18—and specifically its conserved region—plays a key role in stabilizing the interaction of the exons with the spliceosome at the time of exon joining. Superior exon sequences defined by the prp18 results accelerated the second step of splicing by wild-type spliceosomes with inefficient AT-AC pre-mRNAs, implying that normal exon interactions follow the rules we discerned for prp18 splicing. Our results show that As are preferred at the ends of both exons and support a revised model of the interactions of the exons with U5 in which the exons are arranged in a continuous double helix that facilitates the second reaction.
Direct glucocorticoid receptor–Stat5 interaction in hepatocytes controls body size and maturation-related gene expression
Authors: Engblom David , Kornfeld Jan-Wilhelm , Schwake Lukas , Tronche Francois , Reimann Andreas , Beug Hartmut , Hennighausen Lothar , Moriggl Richard , Schütz Günther
Published: May 2007

The glucocorticoid receptor regulates transcription through DNA binding as well as through cross-talk with other transcription factors. In hepatocytes, the glucocorticoid receptor is critical for normal postnatal growth. Using hepatocyte-specific and domain-selective mutations in the mouse we show that Stat5 in hepatocytes is essential for normal postnatal growth and that it mediates the growth-promoting effect of the glucocorticoid receptor through a direct interaction involving the N-terminal tetramerization domain of Stat5b. This interaction mediates a selective and unexpectedly extensive part of the transcriptional actions of these molecules since it controls the expression of gene sets involved in growth and sexual maturation.
Transcription factor modularity in a gene-centered C. elegans core neuronal protein–DNA interaction network
Authors: Vermeirssen Vanessa , Barrasa M. Inmaculada , Hidalgo César A. , Babon Jenny Aurielle B. , Sequerra Reynaldo , Doucette-Stamm Lynn , Barabási Albert-László , Walhout Albertha J.M.
Published: May 2007

Transcription regulatory networks play a pivotal role in the development, function, and pathology of metazoan organisms. Such networks are comprised of protein–DNA interactions between transcription factors (TFs) and their target genes. An important question pertains to how the architecture of such networks relates to network functionality. Here, we show that a Caenorhabditis elegans core neuronal protein–DNA interaction network is organized into two TF modules. These modules contain TFs that bind to a relatively small number of target genes and are more systems specific than the TF hubs that connect the modules. Each module relates to different functional aspects of the network. One module contains TFs involved in reproduction and target genes that are expressed in neurons as well as in other tissues. The second module is enriched for paired homeodomain TFs and connects to target genes that are often exclusively neuronal. We find that paired homeodomain TFs are specifically expressed in C. elegans and mouse neurons, indicating that the neuronal function of paired homeodomains is evolutionarily conserved. Taken together, we show that a core neuronal C. elegans protein–DNA interaction network possesses TF modules that relate to different functional aspects of the complete network.
Thioredoxin-Linked Proteins Are Reduced during Germination ofMedicago truncatulaSeeds
Authors: Alkhalfioui Fatima , Renard Michelle , Vensel William H. , Wong Joshua , Tanaka Charlene K. , Hurkman William J. , Buchanan Bob B. , Montrichard Françoise
Published: May 2007

Germination of cereals is accompanied by extensive change in the redox state of seed proteins. Proteins present in oxidized form in dry seeds are converted to the reduced state following imbibition. Thioredoxin (Trx) appears to play a role in this transition in cereals. It is not known, however, whether Trx-linked redox changes are restricted to cereals or whether they take place more broadly in germinating seeds. To gain information on this point, we have investigated a model legume, Medicago truncatula. Two complementary gel-based proteomic approaches were followed to identify Trx targets in seeds: Proteins were (1) labeled with a thiol-specific probe, monobromobimane (mBBr), following in vitro reduction by an NADP/Trx system, or (2) isolated on a mutant Trx affinity column. Altogether, 111 Trx-linked proteins were identified with few differences between axes and cotyledons. Fifty nine were new, 34 found previously in cereal or peanut seeds, and 18 in other plants or photosynthetic organisms. In parallel, the redox state of proteins assessed in germinating seeds using mBBr revealed that a substantial number of proteins that are oxidized or partly reduced in dry seeds became more reduced upon germination. The patterns were similar for proteins reduced in vivo during germination or in vitro by Trx. In contrast, glutathione and glutaredoxin were less effective as reductants in vitro. Overall, more than half of the potential targets identified with the mBBr labeling procedure were reduced during germination. The results provide evidence that Trx functions in the germination of seeds of dicotyledons as well as monocotyledons.
ABA Is an Essential Signal for Plant Resistance to Pathogens Affecting JA Biosynthesis and the Activation of Defenses inArabidopsis
Authors: Adie Bruce A.T. , Pérez-Pérez Julián , Pérez-Pérez Manuel M. , Godoy Marta , Sánchez-Serrano José-J. , Schmelz Eric A. , Solano Roberto
Published: May 2007

Analyses of Arabidopsis thaliana defense response to the damping-off oomycete pathogen Pythium irregulare show that resistance to P. irregulare requires a multicomponent defense strategy. Penetration represents a first layer, as indicated by the susceptibility of pen2 mutants, followed by recognition, likely mediated by ERECTA receptor-like kinases. Subsequent signaling of inducible defenses is predominantly mediated by jasmonic acid (JA), with insensitive coi1 mutants showing extreme susceptibility. In contrast with the generally accepted roles of ethylene and salicylic acid cooperating with or antagonizing, respectively, JA in the activation of defenses against necrotrophs, both are required to prevent disease progression, although much less so than JA. Meta-analysis of transcriptome profiles confirmed the predominant role of JA in activation of P. irregulare–induced defenses and uncovered abscisic acid (ABA) as an important regulator of defense gene expression. Analysis of cis-regulatory sequences also revealed an unexpected overrepresentation of ABA response elements in promoters of P. irregulare–responsive genes. Subsequent infections of ABA-related and callose-deficient mutants confirmed the importance of ABA in defense, acting partly through an undescribed mechanism. The results support a model for ABA affecting JA biosynthesis in the activation of defenses against this oomycete.
Enhancing the validity and utility of randomized clinical trials in addictions treatment research: III. Data processing and statistical analysis
Authors: Del Boca Frances K. , Darkes Jack
Published: May 2007

Purpose This is the third paper in a series that reviews strategies for optimizing the validity and utility of randomized clinical trials (RCTs) in addictions treatment research. Whereas the two previous papers focused on design and implementation, here we address issues pertaining to data processing and statistical analysis.

Scope Recommendations for enhancing data quality and utility are offered in sections on data coding and entry; and data format, structure and management. We discuss the need for preliminary data analyses that examine statistical power; patterns of attrition; between‐group equivalence; and treatment integrity and discriminability. We discuss tests of treatment efficacy, as well as ancillary analyses aimed at explicating treatment processes.

Conclusions Safeguards are necessary to protect data quality, and advance planning is needed to ensure that data formats are compatible with statistical objectives. In addition to treatment efficacy, statistical analyses should evaluate study internal and external validity, and investigate the change mechanisms that underlie treatment effects.
Detecting signals of drug–drug interactions in a spontaneous reports database
Authors: Thakrar Bharat T. , Grundschober Sabine Borel , Doessegger Lucette
Published: May 2007

Aims

The spontaneous reports database is widely used for detecting signals of ADRs. We have extended the methodology to include the detection of signals of ADRs that are associated with drug–drug interactions (DDI). In particular, we have investigated two different statistical assumptions for detecting signals of DDI.

Methods

Using the FDA's spontaneous reports database, we investigated two models, a multiplicative and an additive model, to detect signals of DDI. We applied the models to four known DDIs (methotrexate‐diclofenac and bone marrow depression, simvastatin‐ciclosporin and myopathy, ketoconazole‐terfenadine and torsades de pointes, and cisapride‐erythromycin and torsades de pointes) and to four drug‐event combinations where there is currently no evidence of a DDI (fexofenadine‐ketoconazole and torsades de pointes, methotrexade‐rofecoxib and bone marrow depression, fluvastatin‐ciclosporin and myopathy, and cisapride‐azithromycine and torsade de pointes) and estimated the measure of interaction on the two scales.

Results

The additive model correctly identified all four known DDIs by giving a statistically significant (P < 0.05) positive measure of interaction. The multiplicative model identified the first two of the known DDIs as having a statistically significant or borderline significant (P < 0.1) positive measure of interaction term, gave a nonsignificant positive trend for the third interaction (P = 0.27), and a negative trend for the last interaction. Both models correctly identified the four known non interactions by estimating a negative measure of interaction.

Conclusions

The spontaneous reports database is a valuable resource for detecting signals of DDIs. In particular, the additive model is more sensitive in detecting such signals. The multiplicative model may further help qualify the strength of the signal detected by the additive model.
Risk of congenital anomalies in pregnant users of statin drugs
Authors: Ofori Benjamin , Rey Evelyne , Bérard Anick
Published: May 2007

What is already known about this subject

• Cholesterol is known to be essential for fetal development.

• Statins, which inhibit cholesterol production, have therefore been considered as potential teratogens and are contraindicated in pregnancy.

• Data available thus far on the risks of congenital anomalies associated with statin therapy have come from non‐analytic postmarketing surveillance studies.

• Given the increasing use of statins in women of childbearing age, there is a need for a population‐based study on the risks of congenital anomalies associated with gestational statin use.

What this study adds

• In this pharmacoepidemiological study, we determined the risk of congenital anomalies in women who filled prescriptions for statins during the first trimester of pregnancy, compared with women who had stopped statins before pregnancy or those who used fibrates during pregnancy.

• We found no evidence of an increased risk of fetal anomalies among first‐trimester statin users, or any discernable pattern of congenital anomalies among live births.

• However, in the absence of outcome data on nonlive births, conclusions remain uncertain.

Aims

Evidence from animal studies suggests that statin medications should not be taken during pregnancy. Our aim was to examine the association between the use of statins in early pregnancy and the incidence of congenital anomalies.

Methods

A population‐based pregnancy registry was built. Three study groups were assembled: women prescribed statins in the first trimester (group A), fibrate/nicotinic acid in the first trimester (group B) and statins between 1 year and 1 month before conception, but not during pregnancy (group C). Among live‐born infants, we selected as cases infants with any congenital anomaly diagnosed in the first year of life. Controls were defined as infants with no congenital anomalies. The rate of congenital anomalies in the respective groups was calculated. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were also calculated.

Results

Our study group consisted of 288 pregnant women. Among women with a live birth, the rate of congenital anomalies was 3/64 (4.69%; 95% CI 1.00, 13.69) in group A, 3/14 in group B (21.43%; 95% CI 4.41, 62.57) and 7/67 in group C (10.45%; 95% CI 4.19, 21.53). The adjusted OR for congenital anomalies in group A compared with group C was 0.36 (95% CI 0.06, 2.18).

Conclusion

We did not detect a pattern in fetal congenital anomalies or evidence of an increased risk in the live‐born infants of women filling prescriptions for statins in the first trimester of pregnancy. Conclusions, however, remain uncertain in the absence of data from nonlive births.
A pharmacokinetic model for L‐carnitine in patients receiving haemodialysis
Authors: Fornasini Gianfranco , Upton Richard N. , Evans Allan M.
Published: May 2007

What is already known about this subject

• Carnitine is essential for fatty acid metabolism, and is obtained from the diet and endogenous synthesis.

• Patients with renal failure who are on chronic haemodialysis may require carnitine supplementation.

• It is known that carnitine depletion in these patients may take years to develop, and that measurements of plasma carnitine may not be predictive of loss of carnitine from muscle, the main pool of carnitine in the body.

What this study adds

• This paper adds a quantitative understanding of the time‐course of the relationship between haemodialysis and the plasma concentration of L‐carnitine, with particular reference to how the carnitine pools in the body re‐equilibrate after a dialysis session.

• It also provides insight into the time‐course of the depletion of L‐carnitine in these patients.

Aims

Patients requiring chronic haemodialysis may develop a secondary carnitine deficiency through dialytic loss of L‐carnitine. A previous report has described the plasma concentrations of L‐carnitine in 12 such patients under baseline conditions and after L‐carnitine administration (20 mg kg−1). A three‐compartment pharmacokinetic model was developed to describe these data to make inferences about carnitine supplementation in these patients.

Methods

L‐carnitine removal was mediated solely by intermittent haemodialysis, which was incorporated into the model as an experimentally derived dialysis clearance value that was linked to an on‐off pulse function. Data were described by a model with a central compartment linked to ‘fast’‐ and ‘slow’‐equilibrating peripheral compartments.

Results

The model adequately described the changing plasma concentrations of endogenous L‐carnitine in individual haemodialysis patients. Based on pooled data (mean ± SD; n = 12), the volume of the central compartment was 10.09 ± 0.72 l and the transfer rate constants into and out of the slowly equilibrating pool were 0.100 ± 0.018 h−1 and 0.00014 ± 0.00016 h−1, respectively. The turnover time of L‐carnitine in the slow pool (which was assumed to represent muscle) was approximately 300 days. The model was in general agreement with separate data on the measured loss of carnitine from muscle in dialysis patients.

Conclusions

Haemodialysis causes rapid reductions in plasma L‐carnitine concentrations with each dialysis session. Plasma concentrations are restored between sessions by redistribution from peripheral compartments. However, during chronic haemodialysis, the ongoing dialytic loss of L‐carnitine may lead to a slow depletion of the compound, contributing to a possible secondary deficiency.
Birthing asynchrony is not a consequence of asynchronous offspring development in a non‐avian vertebrate, the Australian skink Egernia whitii
Authors: WHILE G. M. , JONES S. M. , WAPSTRA E.
Published: May 2007

One of the major impediments to our understanding of avian hatching asynchrony is the difficulty in separating hypotheses that concentrate on the onset of incubation from those that explain hatching asynchrony adaptively. To address this, ideally we need a system(s) in which we can uncouple these two sets of hypotheses. Such a system exists in the skink genus Egernia.

We documented birthing asynchrony (analogous to hatching asynchrony) and the mechanisms underlying birthing asynchrony in the White's skink, Egernia whitii (Lacépède, 1804), a medium‐sized, viviparous skink species that displays complex sociality.

Egernia whitii females gave birth to offspring asynchronously (100% of litters), with an average of >2 days between births. We show that embryo gestation is synchronous with asynchrony first observed at birth. Furthermore, when birth of the entire litter was induced at the birth of the first offspring, there was no difference in development, mass or weight between first (naturally) born offspring and second and third (induced) offspring.

These results suggest that birthing asynchrony in this species is not a consequence of the constraint of asynchronous offspring development, but rather, females retain offspring despite all offspring being fully developed. This suggests that birthing asynchrony in this genus may have an adaptive explanation.

We discuss the potential adaptive explanations of birthing asynchrony in this genus, taking into account the potential links with indirect parental care and social organization, specifically the advantages that birthing asynchrony may offer to offspring in a highly competitive social environment.
Ex vivo microscopic assessment of factors affecting the quality of apical seal created by root‐end fillings
Authors: Tobón‐Arroyave S. I. , Restrepo‐Pérez M. M. , Arismendi‐Echavarría J. A. , Velásquez‐Restrepo Z. , Marín‐Botero M. L. , García‐Dorado E. C.
Published: May 2007

Aim  (i) To evaluate the incidence of microcracks around root‐end preparations completed with ultrasonic tips and their relationship with the root filling technique and thickness of surrounding dentine. (ii) To investigate the effect of rapid exposure to a water‐soluble dye of Intermediate Restorative Material (IRM), Super Ethoxybenzoic Acid (sEBA) and Mineral Trioxide Aggregate (MTA), on the marginal adaptation and microleakage of root‐end fillings. (iii) To describe the microstructure of the surface of root‐end filling materials.

Methodology  Ninety‐two single‐rooted teeth were divided into two groups (n = 46) according to the root canal instrumentation/filling techniques. Group 1 consisted of specimens in which canal preparation was completed using a crown‐down technique and then filled with the Thermafil system (TF group); Group 2 consisted of specimens in which canal preparation was completed using a step‐back technique and lateral condensation (LC group). Following root‐end resection and ultrasonic cavity preparation, the samples were further divided into three subgroups (n = 24) for root‐end filling with IRM, sEBA or MTA. The ultrasonic preparation time was recorded. Eight teeth were kept as positive and 12 as negative controls. Following immersion in Indian ink for 7 days, all resected root surfaces were evaluated for the presence of microcracks and the cross‐sectional area of root‐end surface and root‐end filling were measured to evaluate the thickness of the dentinal walls. Thereafter, the samples were sectioned longitudinally so as to assess the depth of dye penetration and marginal adaptation of root‐end fillings. Negative controls longitudinally sectioned were used to describe microstructural characteristics of the root‐end filling materials using scanning electron microscopic (SEM) techniques.

Results  Although the thickness of dentinal walls between groups 1 and 2 was similar, the ultrasonic preparation time and number of microcracks were significantly higher (P < 0.001) in the TF group. Both groups had a significant correlation between microcracks and ultrasonic preparation time (P < 0.001). sEBA and IRM had better adaptation and less leakage compared with MTA. A SEM analysis displayed microstructural differences between the root‐end filling materials.

Conclusion  Microcracks can occur independently of the thickness of dentinal walls and may be associated with the prolonged ultrasonic preparation time required for the removal of the root filling during root‐end cavity preparation. Although sEBA and IRM had better behaviour than MTA regarding microleakage and marginal adaptation, it is possible that exposure of MTA to a water‐soluble dye before achieving full set and its porous microstructure contributed to the results.
Diet reconstruction and historic population dynamics in a threatened seabird
Authors: NORRIS D. RYAN , ARCESE PETER , PREIKSHOT DAVID , BERTRAM DOUGLAS F. , KYSER T. KURT
Published: May 2007

For the overwhelming majority of species, we lack long‐term information on the dynamics of populations. As a consequence, we face considerable uncertainty about how to discriminate among competing hypotheses of population decline and design conservation plans.

The marbled murrelet Brachyramphus marmoratus is a small seabird that nests in coastal old‐growth forest but feeds year‐round in near‐shore waters of the north‐eastern Pacific. Although a decline in nesting habitat is the primary reason why marbled murrelets are listed as threatened in Canada, nest predation and food availability may also influence population abundance. To examine the hypothesis that murrelet populations are influenced by variation in diet quality, we analysed stable‐carbon and ‐nitrogen isotopes in feathers of museum specimens collected in the Georgia Basin, British Columbia.

Between 1889 and 1996, we found a decline in stable isotopic signatures that was approximately equal to a 62% drop in trophic feeding level. We also found that the estimated proportion of fish in murrelet diet was related closely to murrelet abundance over the past 40 years, as estimated from volunteer surveys. Using these isotopic data, we modelled population size as a function of variation in reproductive rate due to changes in diet quality and found that our model matched closely the 40‐year field estimates. We then applied our 107‐year isotopic record to the model to back‐cast estimates of population growth rate to 1889.

Our results suggest that, up to the 1950s, murrelet populations in the Georgia Basin were capable of growing and were probably limited by factors other than diet quality. After this period, however, our results imply that murrelets were often, but not solely, limited by diet quality.

Synthesis and applications. Protecting nesting habitat may not be sufficient to rebuild populations of this highly secretive and threatened seabird and recovery might also require the restoration of marine habitat quality, as well as a better understanding of how ocean climate affects prey abundance and reproductive rate. Combined with contemporary demographic data, stable isotope analysis of historic samples provides a unique opportunity to reconstruct population histories for species where we lack long‐term information.
Patients’ experiences at home after day case cystoscopy
Authors: Erkal S
Published: May 2007

Aim.  To determine patients’ problems with day case cystoscopy and their problem solving ways and patients’ self‐care at home.

Background.  Day surgery has become increasingly common in the last 20 years. Cystoscopic procedures are increasingly being carried out as a diagnostic and therapeutic procedures.

Design and method.  This descriptive/prospective study comprised 50 patients undergoing day case cystoscopic procedures in the university hospital of Turkey. The data were collected using telephone interview three days after the procedure. The two questionnaire used were Symptom Measurement Questionnaire and Symptom Management Questionnaire. Discharge information and written instruction was given to all patients.

Results.  It was found in the investigation that the most common problems experienced by the patients were tiredness, haematuria, dysuria, pain over bladder and difficulty in voiding after flexible cystoscopy in first day. Generally, urinary elimination problems were experienced by majority of the patients. At second day, these problems were also common. The mean score for all problems decreased after three days. The patients stated that they were able to deal with their symptoms either independently or to a lesser extent with assistance of a carer. But they were unable to deal with problems such as especially haematuria.

Conclusion.  Problems experiences by the patients at home after cystoscopy influenced some daily living activities. The problems related to voiding are more frequently observed after cystoscopy. Although some these problems are related to the procedures, some were present previously.

Relevance to clinical practice.  This findings indicate that patient‐centred care should be strengthened at home in urological day surgery.
The perceived burden among Chinese family caregivers of people with schizophrenia
Authors: Chien Wai‐Tong , Chan Sally WC , Morrissey Jean
Published: May 2007

Aims.  The aim of this study was to examine the level of perceived burden of the Chinese families caring for a relative with schizophrenia and to test its associations with their demographic characteristics, social and family factors and health condition.

Background.  Despite the increased demands on family members to provide care for patients with schizophrenia in community care, little is known about the level of family burden among these family caregivers and its relationship with their demographic, social and cultural backgrounds.

Methods.  This was a cross‐sectional descriptive study. A total of 203 family caregivers were recruited from three regional psychiatric outpatient clinics in Hong Kong. They were asked to complete a set of well‐validated questionnaires, consisting of the Chinese version of four instruments – Family Burden Interview Schedule, Family Assessment Device, Six‐item Social Support Questionnaire and MOS 36‐Item Short Form Health Survey and a socio‐demographic data sheet. Statistical analyses were conducted to test the differences in mean burden scores between subgroups, the inter‐relationships among the mean scores of the scales and socio‐demographic variables and the predictors of family burden.

Results.  The families who perceived a higher level of caregiver burden were those who lived in a family with poorer functioning, worse health status and less satisfaction of social support. The caregivers’ burden score was positively correlated with their age; conversely, it was negatively correlated with their monthly household income and number of family members living with patient. Social support was the best predictor of caregiver burden.

Conclusion.  These findings increase our understanding about the socio‐demographic and cultural variables influencing the well being of family caregivers of a relative with schizophrenia. Helping families to maintain and enhance a supportive social network may represent a useful means to reduce family burden in schizophrenia.

Relevance to clinical practice.  This understanding helps health professionals and researchers to identify different sources and domains of burden from a Chinese cultural perspective and take into account of these factors when planning interventions for family caregivers.
Nurses’ knowledge and skills in colonoscopy patients’ pain management
Authors: Eeva‐Riitta Ylinen , Katri Vehviläinen‐Julkunen , Anna‐Maija Pietilä
Published: May 2007

Aim.  This study aimed to describe the knowledge and skills of nurses in managing pain during colonoscopy procedures.

Background.  Colonoscopy is a procedure to diagnose diseases of the intestine, and patients consider it even painful. However, few studies have described patients’ pain management during the colonoscopy procedure.

Design.  A quantitative survey design was used. The data were collected from colonoscopy nurses with a self‐completed semi‐structured questionnaire developed for the study.

Methods.  The hospitals performing colonoscopies in Finland, with the exception of the ones where the questionnaire was pilot‐tested, were included in the study (n = 12). The optional sample was drawn by mailing questionnaires (n = 147) to endoscopy units to be filled in by three colonoscopy nurses during 2002. The response rate was 79% (n = 116).

Results.  The majority of nurses used versatile non‐pharmacological methods of managing pain and had practice‐based knowledge of pain management during the colonoscopy procedure, but pain education and the acquisition of new professional knowledge were rarely reported. Pain scales were not in use and ethical conversation was lacking among the endoscopy staff in most (95%) hospitals.

Conclusion.  The study showed that colonoscopy nurses used numerous non‐pharmacological methods, but only rarely acquired professional knowledge. There was a lack of pain scales and ethical conversation in the participating endoscopy units.

Relevance to clinical practice.  The results can be used to improve the treatment of pain during colonoscopy procedures and endoscopy nurses’ education. Nurses should be motivated by education and ethical conversation. Future studies should aim to analyse patients’ own evaluation of pain during the colonoscopy procedure. The applicability of the existing pain scales and non‐pharmacological methods should be tested in practice.
Evaluating cardiovascular mortality in type 2 diabetes patients: an analysis based on competing risks Markov Chains and additive regression models
Authors: Rosato Rosalba , Ciccone G. , Bo S. , Pagano G. F. , Merletti F. , Gregori D.
Published: May 2007

Rationale, aims and objectives Type 2 diabetes represents a condition significantly associated with increased cardiovascular mortality. The aims of the study are: (i) to estimate the cumulative incidence function for cause‐specific mortality using Cox and Aalen model; (ii) to describe how the prediction of cardiovascular or other causes mortality changes for patients with different pattern of covariates; (iii) to show if different statistical methods may give different results.

Methods Cox and Aalen additive regression model through the Markov chain approach, are used to estimate the cause‐specific hazard for cardiovascular or other causes mortality in a cohort of 2865 type 2 diabetic patients without insulin treatment. The models are compared in the estimation of the risk of death for patients of different severity.

Results For younger patients with a better covariates profile, the Cumulative Incidence Function estimated by Cox and Aalen model was almost the same; for patients with the worst covariates profile, models gave different results: at the end of follow‐up cardiovascular mortality rate estimated by Cox and Aalen model was 0.26 [95% confidence interval (CI) = 0.21–0.31] and 0.14 (95% CI = 0.09–0.18).

Conclusions Standard Cox and Aalen model capture the risk process for patients equally well with average profiles of co‐morbidities. The Aalen model, in addition, is shown to be better at identifying cause‐specific risk of death for patients with more severe clinical profiles. This result is relevant in the development of analytic tools for research and resource management within diabetes care.
Decision analysis model evaluating the cost‐effectiveness of risperidone, olanzapine and haloperidol in the treatment of schizophrenia
Authors: Bounthavong Mark , Okamoto Mark P.
Published: May 2007

Purpose  To evaluate the cost‐effectiveness of three antipsychotic medications (olanzapine, risperidone and haloperidol) in the treatment of schizophrenia using the Positive and Negative Symptom Scale.

Study design and methods  A decision analysis model was created to evaluate the cost‐effectiveness of two atypical antipsychotics (risperidone and olanzapine) and haloperidol. Outcome probabilities were determined from published clinical trials. The main dependent variable of interest was to compare the incremental cost‐effectiveness ratios (ICER) of the atypical antipsychotic with haloperidol, and also to compare the ICER of olanzapine and risperidone. Sensitivity analyses were conducted for olanzapine and risperidone to determine the effects of altering drug cost, efficacy and re‐hospitalization rate on total costs.

Results  Risperidone and olanzapine were dominant strategies compared with haloperidol (less costly and more effective). Risperidone was also dominant when compared with olanzapine. A one‐way sensitivity analysis for efficacy indicated that the efficacy of risperidone would need to decrease by approximately 3% from the base‐case in order for olanzapine and risperidone to have equal total costs. In a two‐way sensitivity analysis varying both the cost of olanzapine and risperidone, the difference in drug costs between them would have to increase from $2.12 per day to $4.12 per day in order to have equal total costs. In terms of varying re‐hospitalization rates, the re‐hospitalization rate for risperidone would have to increase from 3% to 33% greater than the re‐hospitalization rate for olanzapine in order to have equal total direct costs.

Conclusion  Based on this decision model, atypical antipsychotics were a dominant strategy over haloperidol primarily because of increased efficacy and lower re‐hospitalizations. The ICER indicated that risperidone was dominant over olanzapine because of lower drug costs and increased number of responders, which leads to decreased total costs.
Identification and characterization of the immunity repressor (ImmR) that controls the mobile genetic element ICEBs1 of Bacillus subtilis
Authors: Auchtung Jennifer M. , Lee Catherine A. , Garrison Katherine L. , Grossman Alan D.
Published: May 2007

ICEBs1 is a mobile genetic element found in the chromosome of Bacillus subtilis. Excision and transfer of ICEBs1 is regulated by the global DNA damage response and intercellular peptide signalling. We identified and characterized a repressor, ImmR (formerly YdcN), encoded by ICEBs1. ImmR represses transcription of genes required for excision and transfer, and both activates and represses its own transcription. ImmR regulates transcription within ICEBs1 by binding to several sites in the region of DNA that contains promoters for both immR and xis (encoding excisionase). In addition, we found that ImmR confers immunity from acquisition of additional copies of ICEBs1. ImmR‐mediated regulation serves to keep a single copy of ICEBs1 stably maintained in the absence of induction, allows a rapid response to inducing signals, and helps limit acquisition of additional copies of ICEBs1.
Structural asymmetry and discrete nucleic acid subdomains in the Trypanosoma brucei kinetoplast
Authors: Gluenz Eva , Shaw Michael K. , Gull Keith
Published: May 2007

The mitochondrial genome of Trypanosoma brucei is contained in a specialized structure termed the kinetoplast. Kinetoplast DNA (kDNA) is organized into a concatenated network of mini and maxicircles, positioned at the base of the flagellum, to which it is physically attached. Here we have used electron microscope cytochemistry to determine structural and functional domains involved in replication and segregation of the kinetoplast. We identified two distinct subdomains within the kinetoflagellar zone (KFZ) and show that the unilateral filaments are composed of distinct inner and outer filaments. Ethanolic phosphotungstic acid (E‐PTA) and EDTA regressive staining indicate that basic proteins and DNA are major constituents of the inner unilateral filaments adjoining the kDNA disc. This evidence for an intimate connection of the unilateral filaments in the KFZ with DNA provides support for models of minicircle replication involving vectorial export of free minicircles into the KFZ. Unexpectedly however, detection of DNA in the KFZ throughout the cell cycle suggests that other processes involving kDNA occur in this domain. We also describe a hitherto unrecognized, intramitochondrial, filamentous structure rich in basic proteins that links the kDNA discs during their segregation and is maintained between them for an extended period of the cell cycle.
Mercurochrome allergy. Immediate and delayed hypersensitivity
Authors: Galindo P. A. , Feo F. , García R. , Gómez E. , Borja J. , Fernández F.
Published: May 2007

We describe eight patients suffering from Mercurochrome allergy. Patch and prick tests were carried out with the following organic and inorganic mercury compounds: thimerosal, Mercurochrome, phenylmercuric acetate, phenylmercuric nitrate, metallic mercury, and mercuric chloride, and with sodium fluorescein. Two patients had an anaphylactic reaction a few minutes after application of Mercurochrome. The prick tests with Mercurochrome were positive and they were negative with the other tested products. All patch tests were negative. In the other six patients, the clinical picture was local eczema, and the patch tests were all positive with Mercurochrome and the inorganic mercuric derivatives. Positive patch tests with thimerosal were found only in two patients, and only one had a positive patch test with salts of phenylmercury. In four patients, the prick test with Mercurochrome, negative in immediate reading, gave a late eczematous reaction.
Microvascular hepatic artery reconstruction in pediatric abdominal transplantation: Pearls and pitfalls
Authors: Bodor Richard , Greenberg Joshua I. , Abrams Reid A. , Obiekwe Sam , Hart Marquis , Lavine Joel E. , Khanna Ajai
Published: May 2007

Abstract:  The “back‐wall first” hepatic artery microanastomosis in pediatric liver transplantation saves lives and reduces morbidity. We describe our technique of hepatic artery reconstruction and offer a systematic and multi‐team collaborative approach that optimizes surgical outcomes.