Effectiveness of Myocardial Contrast Echocardiography Quantitative Analysis during Adenosine Stress versus Visual Analysis before Percutaneous Therapy in Acute Coronary Pain: A Coronary Artery TIMI Grading Comparing Study

The study aim was to compare two different stress echocardiography interpretation techniques based on the correlation with thrombosis in myocardial infarction (TIMI) flow grading from acute coronary syndrome (ACS) patients. Forty-one patients with suspected ACS were studied before diagnostic coronary angiography with myocardial contrast echocardiography (MCE) at rest and at stress. The correlation of visual interpretation of MCE and TIMI flow grade was significant. The quantitative analysis (myocardial perfusion parameters: A, beta, and A x beta) and TIMI flow grade were significant. MCE visual interpretation and TIMI flow grade had a high degree of agreement, on diagnosing myocardial perfusion abnormality. If one considers TIMI flow grade <3 as abnormal, MCE visual interpretation at rest had 73.1% accuracy with 58.2% sensitivity and 84.2% specificity and at stress had 80.4% accuracy with 76.6% sensitivity and 83.3% specificity. The MCE quantitative analysis has better accuracy with 100% of agreement with different level of TIMI flow grading. MCE quantitative analysis at stress has showed a direct correlation with TIMI flow grade, more significant than the visual interpretation technique. Further studies could measure the clinical relevance of this more objective approach to managing acute coronary syndrome patient before percutaneous coronary intervention (PCI).Science and Technology Planning Project Grant of Urumqi Municipality of the Xinjiang Uygur Autonomous Region [G06131001]Science and Technology Planning Project Grant of Urumqi Municipality of the Xinjiang Uygur Autonomous Region [G06131001

Ancestral Components of Admixed Genomes in a Mexican Cohort

For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people

The Effect of the CO32- to Ca2+ Ion activity ratio on calcite precipitation kinetics and Sr2+ partitioning

<p>Abstract</p> <p>Background</p> <p>A proposed strategy for immobilizing trace metals in the subsurface is to stimulate calcium carbonate precipitation and incorporate contaminants by co-precipitation. Such an approach will require injecting chemical amendments into the subsurface to generate supersaturated conditions that promote mineral precipitation. However, the formation of reactant mixing zones will create gradients in both the saturation state and ion activity ratios (i.e., <inline-formula><m:math name="1467-4866-13-1-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:msub><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mi>C</m:mi><m:msup><m:mrow><m:msub><m:mrow><m:mi>O</m:mi></m:mrow><m:mrow><m:mn>3</m:mn></m:mrow></m:msub></m:mrow><m:mrow><m:mn>2</m:mn><m:mo class="MathClass-bin">-</m:mo></m:mrow></m:msup></m:mrow></m:msub><m:mo class="MathClass-bin">/</m:mo><m:msub><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mi>C</m:mi><m:msup><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mn>2</m:mn><m:mo class="MathClass-bin">+</m:mo></m:mrow></m:msup></m:mrow></m:msub></m:math></inline-formula>). To better understand the effect of ion activity ratios on CaCO₃precipitation kinetics and Sr²⁺co-precipitation, experiments were conducted under constant composition conditions where the supersaturation state (Ω) for calcite was held constant at 9.4, but the ion activity ratio <inline-formula><m:math name="1467-4866-13-1-i2" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:mrow><m:mo class="MathClass-open">(</m:mo><m:mrow><m:mi>r</m:mi><m:mo class="MathClass-rel">=</m:mo><m:msub><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mi>C</m:mi><m:msup><m:mrow><m:msub><m:mrow><m:mi>O</m:mi></m:mrow><m:mrow><m:mn>3</m:mn></m:mrow></m:msub></m:mrow><m:mrow><m:mn>2</m:mn><m:mo class="MathClass-bin">-</m:mo></m:mrow></m:msup></m:mrow></m:msub><m:mo class="MathClass-bin">/</m:mo><m:msub><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mi>C</m:mi><m:msup><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mn>2</m:mn><m:mo class="MathClass-bin">+</m:mo></m:mrow></m:msup></m:mrow></m:msub></m:mrow><m:mo class="MathClass-close">)</m:mo></m:mrow></m:math></inline-formula> was varied between 0.0032 and 4.15.</p> <p>Results</p> <p>Calcite was the only phase observed, by XRD, at the end of the experiments. Precipitation rates increased from 41.3 ± 3.4 μmol m^-2min^-1at <it>r = </it>0.0315 to a maximum rate of 74.5 ± 4.8 μmol m^-2min^-1at <it>r = </it>0.306 followed by a decrease to 46.3 ± 9.6 μmol m^-2min^-1at <it>r </it>= 1.822. The trend was simulated using a simple mass transfer model for solute uptake at the calcite surface. However, precipitation rates at fixed saturation states also evolved with time. Precipitation rates accelerated for low <it>r </it>values but slowed for high <it>r </it>values. These trends may be related to changes in effective reactive surface area. The <inline-formula><m:math xmlns:m="http://www.w3.org/1998/Math/MathML" name="1467-4866-13-1-i1"><m:msub><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mi>C</m:mi><m:msup><m:mrow><m:msub><m:mrow><m:mi>O</m:mi></m:mrow><m:mrow><m:mn>3</m:mn></m:mrow></m:msub></m:mrow><m:mrow><m:mn>2</m:mn><m:mo class="MathClass-bin">-</m:mo></m:mrow></m:msup></m:mrow></m:msub><m:mo class="MathClass-bin">/</m:mo><m:msub><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mi>C</m:mi><m:msup><m:mrow><m:mi>a</m:mi></m:mrow><m:mrow><m:mn>2</m:mn><m:mo class="MathClass-bin">+</m:mo></m:mrow></m:msup></m:mrow></m:msub></m:math></inline-formula> ratios did not affect the distribution coefficient for Sr in calcite (D^P_Sr²⁺), apart from the indirect effect associated with the established positive correlation between D^P_Sr²⁺and calcite precipitation rate.</p> <p>Conclusion</p> <p>At a constant supersaturation state (Ω = 9.4), varying the ion activity ratio affects the calcite precipitation rate. This behavior is not predicted by affinity-based rate models. Furthermore, at the highest ion ratio tested, no precipitation was observed, while at the lowest ion ratio precipitation occurred immediately and valid rate measurements could not be made. The maximum measured precipitation rate was 2-fold greater than the minima, and occurred at a carbonate to calcium ion activity ratio of 0.306. These findings have implications for predicting the progress and cost of remediation operations involving enhanced calcite precipitation where mineral precipitation rates, and the spatial/temporal distribution of those rates, can have significant impacts on the mobility of contaminants.</p

The influences of patient's trust in medical service and attitude towards health policy on patient's overall satisfaction with medical service and sub satisfaction in China

<p>Abstract</p> <p>Background</p> <p>It is widely accepted that patient generates overall satisfaction with medical service and sub satisfaction on the basis of response to patient's trust in medical service and response to patient's attitude towards health policy in China. This study aimed to investigate the correlations between patient's trust in medical service/patient's attitude towards health policy and patient's overall satisfaction with medical service/sub satisfaction in current medical experience and find inspiration for future reform of China's health delivery system on improving patient's overall satisfaction with medical service and sub satisfaction in considering patient's trust in medical service and patient's attitude towards health policy.</p> <p>Methods</p> <p>This study collaborated with the National Bureau of Statistics to collect a sample of 3,424 residents from 17 provinces and municipalities in a 2008 China household survey on patient's trust in medical service, patient's attitude towards health policy, patient's overall satisfaction and sub satisfaction in current medical experience.</p> <p>Results</p> <p>Patient's overall satisfaction with medical service and most kinds of sub satisfaction in current medical experience were significantly influenced by both patient's trust in medical service and patient's attitude towards health policy; among all kinds of sub satisfaction in current medical experience, patient's trust in medical service/patient's attitude towards health policy had the largest influence on patient's satisfaction with medical costs, the influences of patient's trust in medical service/patient's attitude towards health policy on patient's satisfaction with doctor-patient interaction and satisfaction with treatment process were at medium-level, patient's trust in medical service/patient's attitude towards health policy had the smallest influence on patient's satisfaction with medical facilities and hospital environment, while patient's satisfaction with waiting time in hospital was not influenced by patient's trust in medical service/patient's attitude towards health policy.</p> <p>Conclusion</p> <p>In order to improve patient's overall satisfaction with medical service and sub satisfaction in considering patient's trust in medical service and patient's attitude towards health policy, both improving patient's interpersonal trust in medical service from individual's own medical experience/public trust in medical service and improving patient's attitude towards health policy were indirect but effective ways.</p

Urinary Bisphenol A and Type-2 Diabetes in U.S. Adults: Data from NHANES 2003-2008

Bisphenol A (BPA) is found in plastics and other consumer products; exposure may lead to insulin resistance and development of type-2 diabetes mellitus (T2DM) through over-activation of pancreatic β-cells. Previous studies using data from the National Health and Nutrition Examination Survey (NHANES) showed an inconsistent association between prevalence of self-reported T2DM and urinary BPA. We used a different diagnosis method of T2DM (hemoglobin A1c (HbA1c)) with a larger subset of NHANES.We analyzed data from 4,389 adult participants who were part of a sub-study of environmental phenol measurements in urine from three NHANES cycles from 2003 to 2008. T2DM was defined as having a HbA1c ≥6.5% or use of diabetes medication. The weighted prevalence of T2DM was 9.2%. Analysis of the total sample revealed that a two-fold increase in urinary BPA was associated with an odds ratio (OR) of 1.08 of T2DM (95% confidence interval (CI), 1.02 to 1.16), after controlling for potential confounders. However, when we examined each NHANES cycle individually, we only found a statistically significant association in the 2003/04 cycle (n = 1,364, OR = 1.23 (95% CI, 1.07 to 1.42) for each doubling in urinary BPA). We found no association in either the NHANES cycle from 2005/06 (n = 1,363, OR = 1.05 (95% CI, 0.94 to 1.18)); or 2007/08 (n = 1,662, OR = 1.06 (95% CI, 0.91 to 1.23)). Similar patterns of associations between BPA and continuous HbA1c were also observed.Although higher urinary BPA was associated with elevated HbA1c and T2DM in the pooled analysis, it was driven by data from only one NHANES cycle. Additional studies, especially of a longitudinal design with repeated BPA measurements, are needed to further elucidate the association between BPA and T2DM

PKCε Stimulated Arginine Methylation of RIP140 for Its Nuclear-Cytoplasmic Export in Adipocyte Differentiation

Receptor interacting protein 140 (RIP140) is a versatile transcriptional co-repressor that plays roles in diverse metabolic processes including fat accumulation in adipocytes. Previously we identified three methylated arginine residues in RIP140, which rendered its export to the cytoplasm; but it was unclear what triggered RIP140 arginine methylation.In this study, we determined the activated PKCepsilon as the specific trigger for RIP140 arginine methylation and its subsequent export. We identified two PKCepsilon-phosphorylated residues of RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the nuclear gene-repressive activity of RIP140 was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation was effectively rescued by the phosphorylation-deficient mutant RIP140 that resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140 that was exported to the cytoplasm.This study uncovers a novel means, via a cascade of protein modifications, to inactivate, or suppress, the nuclear action of an important transcription coregulator RIP140, and delineates the first specific phosphorylation-arginine methylation cascade that could alter protein subcellular distribution and biological activity

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs

RNA interference (RNAi)-based gene silencing is widely used in laboratories for gene function studies and also holds a great promise for developing treatments for diseases. However, in vivo delivery of RNAi therapy remains a key issue. Lentiviral vectors have been employed for stable gene transfer and gene therapy and therefore are expected to deliver a stable and durable RNAi therapy. But this does not seem to be true in some disease models. Here, we showed that lentivirus delivered short-hairpin RNA (shRNA) against human papillomavirus (HPV) E6/E7 oncogenes were effective for only 2 weeks in a cervical cancer model. However, using this vector to carry two copies of the same shRNA or two shRNAs targeting at two different but closely related genes (HPV E6 and vascular endothelial growth factor) was more effective at silencing the gene targets and inhibiting cell or even tumor growth than their single shRNA counterparts. The cancer cells treated with dual shRNA were also more sensitive to chemotherapeutic drugs than single shRNA-treated cells. These results suggest that a multi-shRNA strategy may be a more attractive approach for developing an RNAi therapy for this cancer. Cancer Gene Therapy (2011) 18, 219-227; doi: 10.1038/cgt.2010.72; published online 19 November 201

The APEX Quantitative Proteomics Tool: Generating protein quantitation estimates from LC-MS/MS proteomics results

Mass spectrometry (MS) based label-free protein quantitation has mainly focused on analysis of ion peak heights and peptide spectral counts. Most analyses of tandem mass spectrometry (MS/MS) data begin with an enzymatic digestion of a complex protein mixture to generate smaller peptides that can be separated and identified by an MS/MS instrument. Peptide spectral counting techniques attempt to quantify protein abundance by counting the number of detected tryptic peptides and their corresponding MS spectra. However, spectral counting is confounded by the fact that peptide physicochemical properties severely affect MS detection resulting in each peptide having a different detection probability. Lu et al. (2007) described a modified spectral counting technique, Absolute Protein Expression (APEX), which improves on basic spectral counting methods by including a correction factor for each protein (called O(i) value) that accounts for variable peptide detection by MS techniques. The technique uses machine learning classification to derive peptide detection probabilities that are used to predict the number of tryptic peptides expected to be detected for one molecule of a particular protein (O(i)). This predicted spectral count is compared to the protein's observed MS total spectral count during APEX computation of protein abundances. Results: The APEX Quantitative Proteomics Tool, introduced here, is a free open source Java application that supports the APEX protein quantitation technique. The APEX tool uses data from standard tandem mass spectrometry proteomics experiments and provides computational support for APEX protein abundance quantitation through a set of graphical user interfaces that partition thparameter controls for the various processing tasks. The tool also provides a Z-score analysis for identification of significant differential protein expression, a utility to assess APEX classifier performance via cross validation, and a utility to merge multiple APEX results into a standardized format in preparation for further statistical analysis. Conclusion: The APEX Quantitative Proteomics Tool provides a simple means to quickly derive hundreds to thousands of protein abundance values from standard liquid chromatography-tandem mass spectrometry proteomics datasets. The APEX tool provides a straightforward intuitive interface design overlaying a highly customizable computational workflow to produce protein abundance values from LC-MS/MS datasets.National Institute of Allergy and Infectious Diseases (NIAID) N01-AI15447National Institutes of HealthNational Science Foundation, the Welsh and Packard FoundationsInternational Human Frontier Science ProgramCenter for Systems and Synthetic Biolog