bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incremental value of contrast myocardial perfusion to detect intermediate versus severe coronary artery stenosis during stress-echocardiography
Authors: Gaibazzi Nicola , Rigo Fausto , Squeri Angelo , Ugo Fabrizio , Reverberi Claudio 
Published: May 2010

Abstract

Background
We aimed to compare the incremental value of contrast myocardial perfusion imaging (MPI) for the detection of intermediate versus severe coronary artery stenosis during dipyridamole-atropine echocardiography (DASE).
Wall motion (WM) assessment during stress-echocardiography demonstrates suboptimal sensitivity to detect coronary artery disease (CAD), particularly in patients with isolated intermediate (50%-70%) coronary stenosis.

Methods
We performed DASE with MPI in 150 patients with a suspected chest pain syndrome who were given clinical indication to coronary angiography.

Results and discussion
When CAD was defined as the presence of a ≥50% stenosis, the addition of MPI increased sensitivity (+30%) and decreased specificity (-14%), with a final increase in total diagnostic accuracy (+16%, p < 0.001). The addition of MPI data substantially increased the sensitivity to detect patients with isolated intermediate stenosis from 37% to 98% (p < 0.001); the incremental sensitivity was much lower in patients with severe stenosis, from 85% to 96% (p < 0.05), at the expense of a higher decrease in specificity and a final decrease in total diagnostic accuracy (-18%, p < 0.001).

Conclusions
The addition of MPI on top of WM analysis during DASE increases the diagnostic sensitivity to detect obstructive CAD, whatever its definition (≥50% or > 70% stenosis), but it is mainly driven by the sensitivity increase in the intermediate group (50%-70% stenosis).
The total diagnostic accuracy increased only when defining CAD as ≥50% stenosis, since in patients with severe stenosis (> 70%) the decrease in specificity is not counterbalanced by the minor sensitivity increase.
Membrane-initiated actions of estradiol (E2) in the regulation of LH secretion in ovariectomized (OVX) ewes
Authors: Arreguin-Arevalo J Alejandro , Ashley Ryan L , Wagenmaker Elizabeth R , Oakley Amy E , Karsch Fred J , Nett Terry M 
Published: May 2010

Abstract

Background
We demonstrated that E2 conjugated to BSA (E2BSA) induces a rapid membrane-initiated inhibition of LH secretion followed hours later by a slight increase in LH secretion. Whether these actions of E2BSA are restricted to the pituitary gland and whether the membrane-initiated pathway of E2BSA contributes to the up-regulation of the number of GnRH receptors during the positive feedback effect of E2 were evaluated here. We have shown that the suppression of LH secretion induced by E2 and E2BSA is the result of a decreased responsiveness of the pituitary gland to GnRH. In this study we further tested the ability of E2BSA to decrease the responsiveness of the pituitary gland to GnRH under the paradigm of the preovulatory surge of LH induced by E2.

Methods
For the first experiment GnRH and LH secretions were determined in samples of pituitary portal and jugular blood, respectively, in ewes treated with 12 mg E2BSA. In the second experiment, the number of GnRH receptors was quantified in ewes 12 h after administration of 25 micrograms E2 (the expected time for the increase in the number of GnRH receptors and the positive feedback effect of E2 in LH secretion) or 12 mg E2BSA. In the third experiment, the preovulatory-like surge of LH was characterized in ewes injected with 25 micrograms E2 alone or followed 8 h later (before the beginning of the LH surge) with 60 mg E2BSA.

Results
a) the decrease in LH secretion induced by E2BSA was not accompanied by changes in the pulsatile pattern of GnRH, b) E2BSA increased the number of GnRH receptors, and c) the presence of E2BSA in E2-treated ewes delayed the onset, reduced the length, and decreased the amount of LH released during the preovulatory surge of LH.

Conclusions
a) the rapid suppression of LH secretion induced by E2BSA is mediated only via a direct action on the pituitary gland, b) E2 acting via a membrane-initiated pathway contributes to increase the number of GnRH receptors and, c) administration of E2BSA near the beginning of the pre-ovulatory surge of LH delays and reduces the magnitude of the surge.
What is my walking neighbourhood? A pilot study of English adults' definitions of their local walking neighbourhoods
Authors: Smith Graham , Gidlow Christopher , Davey Rachel , Foster Charles 
Published: May 2010

Abstract

Background
Existing measures of perceptions of the environment associated with walking commonly rely on providing a definition of 'neighbourhood', e.g. 1 mile area around the home. We have little understanding of how these examples relate with adults' own geographical definitions of their neighbourhood area. Our pilot study examined the congruence between definitions used in environmental questionnaires and adults' own definitions of neighbourhood.

Methods
We conducted 58 face-to-face interviews with participants randomly selected from 10 areas of Stoke-on-Trent, England. Participants were shown printed maps showing their local area with road names and places of interest (e.g. shops, services, green space) and were asked: (i) to recall usual walking destinations (from their home); (ii) to draw their 'neighbourhood walking area' on the map. Annotated maps were scanned back into GIS for analysis.

Results
When asked to draw their 'neighbourhood' boundary, the resulting area drawn by participants on average represented only 16 ± 20% of the commonly used total straight-line buffer of 1 mile (or 1.6 km) with a range of 0.3% to 111%. Even when repeated using a network buffer (rather than straight-line) the same comparison resulted in a mean of 36% (± 47%) and a range of 0.6 to 245%.

Conclusions
We found that adults' interpretation of their neighbourhood area does not appear to relate accurately to the definitions typically used in research into environmental perceptions and walking. This mis-match warrants further investigation as definitions used in existing measures may be consistently misclassifying perceived local walking neighbourhoods.
Stepwise mechanism for transcription fidelity
Authors: Yuzenkova Yulia , Bochkareva Aleksandra , Tadigotla Vasisht R , Roghanian Mohammad , Zorov Savva , Severinov Konstantin , Zenkin Nikolay 
Published: May 2010

Abstract

Background
Transcription is the first step of gene expression and is characterized by a high fidelity of RNA synthesis. During transcription, the RNA polymerase active centre discriminates against not just non-complementary ribo NTP substrates but also against complementary 2'- and 3'-deoxy NTPs. A flexible domain of the RNA polymerase active centre, the Trigger Loop, was shown to play an important role in this process, but the mechanisms of this participation remained elusive.

Results
Here we show that transcription fidelity is achieved through a multi-step process. The initial binding in the active centre is the major discrimination step for some non-complementary substrates, although for the rest of misincorporation events discrimination at this step is very poor. During the second step, non-complementary and 2'-deoxy NTPs are discriminated against based on differences in reaction transition state stabilization and partly in general base catalysis, for correct versus non-correct substrates. This step is determined by two residues of the Trigger Loop that participate in catalysis. In the following step, non-complementary and 2'-deoxy NTPs are actively removed from the active centre through a rearrangement of the Trigger Loop. The only step of discrimination against 3'-deoxy substrates, distinct from the ones above, is based on failure to orient the Trigger Loop catalytic residues in the absence of 3'OH.

Conclusions
We demonstrate that fidelity of transcription by multi-subunit RNA polymerases is achieved through a stepwise process. We show that individual steps contribute differently to discrimination against various erroneous substrates. We define the mechanisms and contributions of each of these steps to the overall fidelity of transcription.
A simple powerful bivariate test for two sample location problems in experimental and observational studies
Authors: Tabesh Hamed , Ayatollahi S MT , Towhidi Mina 
Published: May 2010

AbstractBackgroundIn many areas of medical research, a bivariate analysis is desirable because it simultaneously tests two response variables that are of equal interest and importance in two populations. Several parametric and nonparametric bivariate procedures are available for the location problem but each of them requires a series of stringent assumptions such as specific distribution, affine-invariance or elliptical symmetry.The aim of this study is to propose a powerful test statistic that requires none of the aforementioned assumptions. We have reduced the bivariate problem to the univariate problem of sum or subtraction of measurements. A simple bivariate test for the difference in location between two populations is proposed.MethodIn this study the proposed test is compared with Hotelling'sT2test, two sample Rank test, Cramer test for multivariate two sample problem and Mathur's test using Monte Carlo simulation techniques. The power study shows that the proposed test performs better than any of its competitors for most of the populations considered and is equivalent to the Rank test in specific distributions.ConclusionsUsing simulation studies, we show that the proposed test will perform much better under different conditions of underlying population distribution such as normality or non-normality, skewed or symmetric, medium tailed or heavy tailed. The test is therefore recommended for practical applications because it is more powerful than any of the alternatives compared in this paper for almost all the shifts in location and in any direction.
Radiotherapy of large target volumes in Hodgkin's lymphoma: normal tissue sparing capability of forward IMRT versus conventional techniques
Authors: Cella Laura , Liuzzi Raffaele , Magliulo Mario , Conson Manuel , Camera Luigi , Salvatore Marco , Pacelli Roberto 
Published: May 2010

Abstract

Background
This paper analyses normal tissue sparing capability of radiation treatment techniques in Hodgkin's lymphoma with large treatment volume.

Methods
10 patients with supradiaphragmatic Hodgkin's lymphoma and planning target volume (PTV) larger than 900 cm3 were evaluated. Two plans were simulated for each patient using 6 MV X-rays: a conventional multi-leaf (MLC) parallel-opposed (AP-PA) plan, and the same plan with additional MLC shaped segments (forward planned intensity modulated radiation therapy, FPIMRT). In order to compare plans, dose-volume histograms (DVHs) of PTV, lungs, heart, spinal cord, breast, and thyroid were analyzed. The Inhomogeneity Coefficient (IC), the PTV receiving 95% of the prescription dose (V95), the normal tissue complication probability (NTCP) and dose-volume parameters for the OARs were determined.

Results
the PTV coverage was improved (mean V95AP-PA = 95.9 and ICAP-PA = 0.4 vs. V95FPIMRT = 96.8 and ICFPIMRT = 0.31, p ≤ 0.05) by the FPIMRT technique compared to the conventional one. At the same time, NTCPs of lung, spinal cord and thyroid, and the volume of lung and thyroid receiving ≥ 30 Gy resulted significantly reduced when using the FPIMRT technique.

Conclusions
The FPIMRT technique can represent a very useful and, at the same time, simple method for improving PTV conformity while saving critical organs when large fields are needed as in Hodgkin's lymphoma.
Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation
Authors: Tang Y Amy , Huntley Derek , Montana Giovanni , Cerase Andrea , Nesterova Tatyana B , Brockdorff Neil 
Published: May 2010

Abstract

Background
X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes.

Results
Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing.

Conclusions
This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis.
Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways
Authors: Lim Elgene , Wu Di , Pal Bhupinder , Bouras Toula , Asselin-Labat Marie-Liesse , Vaillant François , Yagita Hideo , Lindeman Geoffrey J , Smyth Gordon K , Visvader Jane E 
Published: May 2010

Abstract
Introduction
Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks.

Methods
RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways.

Results
The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets.

Conclusions
The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models.
The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum
Authors: Piechota Marcin , Korostynski Michal , Solecki Wojciech , Gieryk Agnieszka , Slezak Michal , Bilecki Wiktor , Ziolkowska Barbara , Kostrzewa Elzbieta , Cymerman Iwona , Swiech Lukasz , Jaworski Jacek , Przewlocki Ryszard 
Published: May 2010

AbstractBackgroundVarious drugs of abuse activate intracellular pathways in the brain reward system. These pathways regulate the expression of genes that are essential to the development of addiction. To reveal genes common and distinct for different classes of drugs of abuse, we compared the effects of nicotine, ethanol, cocaine, morphine, heroin and methamphetamine on gene expression profiles in the mouse striatum.ResultsWe applied whole-genome microarray profiling to evaluate detailed time-courses (1, 2, 4 and 8 hours) of transcriptome alterations following acute drug administration in mice. We identified 42 drug-responsive genes that were segregated into two main transcriptional modules. The first module consisted of activity-dependent transcripts (includingFosandNpas4), which are induced by psychostimulants and opioids. The second group of genes (includingFkbp5andS3-12), which are controlled, in part, by the release of steroid hormones, was strongly activated by ethanol and opioids. Using pharmacological tools, we were able to inhibit the induction of particular modules of drug-related genomic profiles. We selected a subset of genes for validation byin situhybridization and quantitative PCR. We also showed that knockdown of the drug-responsive genesSgk1andTsc22d3resulted in alterations to dendritic spines in mice, possibly reflecting an altered potential for plastic changes.ConclusionsOur study identified modules of drug-induced genes that share functional relationships. These genes may play a critical role in the early stages of addiction.
Drug Name Mix-up/Wrong Insulin Concentration/Access to Ambulatory Lab Info Only Includes Prescribers/Errors with Insulin/is it “Units” or “4”?/Root Cause Analysis Published
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: May 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Treatment of Methicillin-Resistant Staphylococcus Aureus with a Vancomycin Minimum Inhibitory Concentration of 2 mcg/mL
Authors: Kettle Jacob K. , Grace Jason W. , Schaefer R. Spencer , Desai Arundhati 
Published: May 2010

Background Vancomycin has been considered the standard of therapy for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) for decades. The aims of this study were to describe the clinical outcomes of patients with infections caused by MRSA with a vancomycin minimum inhibitory concentration (MIC) of 2 mcg/mL and determine whether achievement of a high vancomycin trough concentration affected outcomes. Methods A retrospective analysis was conducted on data from a single medical center from 2003 through 2007. The study included patients with a culture positive for MRSA with a vancomycin MIC of 2 mcg/mL who received vancomycin therapy. Treatment groups were determined by weighted average vancomycin trough concentration. Subjects were assigned to either the conventional (less than 15 mcg/mL) or high (15 mcg/mL or higher) trough group. Outcome measures included attainment of clinical cure, all-cause mortality, and occurrence of nephrotoxicity. Results Of the 79 patients included in the study, 50 (63.3%) attained clinical cure. Rate of clinical cure was similar between the conventional and high trough groups (64.7% vs 60.7%, P = 0.7). Treatment arms were similar in regard to all-cause mortality and other secondary endpoints. Patients demonstrating clinical response at 72 hours were significantly more likely to progress to clinical cure than those continuing to show signs of infection (77.8% vs 32.5, P < 0.001). Conclusions Use of vancomycin for the treatment of MRSA with a vancomycin MIC of 2 mcg/mL resulted in a low rate of clinical cure. Data from this study suggest that achieving higher vancomycin trough concentrations is not a sufficient strategy for enhancing efficacy in these challenging infections.
Value of Board Certification in the Hospital Setting: A Survey of Academic and Nonacademic Medical Centers
Authors: Smith Andrew J. , Huke Michael , Rasu Rafia S. 
Published: May 2010

Purpose The aim of this study was to assess the current attitudes toward pharmacist specialty board certification in an array of hospital practice settings as perceived by directors of pharmacy (DOP) and to identify incentives available to pharmacists to become board certified. Methods A seven-question survey was developed that assessed demographic information along with information regarding overall value of board certification in the view of the institution. The types of incentives provided to become a board-certified pharmacist were also evaluated. The survey was administered via the Internet to 295 DOPs within two large listserves, the University HealthSystem Consortium and Pharmacy Systems, Inc. Responses were collected for a total of 4 weeks, with a reminder e-mail sent 2 weeks after survey distribution to encourage survey completion. Results A total of 85 DOPs completed the survey. Academic institutions (AIs) had a higher percentage of board-certified pharmacists versus nonacademic institutions (NAIs) (26% vs 6%, P < 0.001). DOPs at AIs placed a higher value on board certification than DOPs at NAIs (93% vs 39%, P < 0.001). AIs were nearly eight times more likely to provide at least one incentive to become board certified compared to NAIs (odds ratio, 7.87; 95% confidence interval, 1.18 to 52.5; P = 0.033). Conclusions This investigation demonstrates a lack of dissemination of the benefits of board certification into NAIs. Efforts should be increased to show the value of specialty board certification outside the arena of AIs.