NO ASSOCIATION OF PARAOXONASE-1 Q192R AND THROMBOTIC EVENTS DURING DUAL ANTI-PLATELET THERAPY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION

Personalised Therapeutic

Supporting the massive scale-up of antiretroviral therapy: the evolution of PEPFAR-supported treatment facilities in South Africa, 2005-2009

<p>Abstract</p> <p>Background</p> <p>South Africa has an estimated 1.5 million persons in need of antiretroviral therapy (ART). In 2004, the South African government began collaborating with the United States President's Emergency Plan for AIDS Relief (PEPFAR) to increase access to ART. We determined how PEPFAR treatment support changed from 2005-2009.</p> <p>Methods</p> <p>In order to describe the change in number and type of PEPFAR-supported ART facilities, we analyzed routinely collected program-monitoring data from 2005-2009. The collected data included the number, type and province of facilities as well as the number of patients receiving ART at each facility.</p> <p>Results</p> <p>The number of PEPFAR-supported facilities providing ART increased from 184 facilities in 2005 to 1,469 facilities in 2009. From 2005-2009 the number of PEPFAR-supported government facilities increased 10.1 fold from 54 to 546 while the number of PEPFAR-supported NGO facilities (including general practitioner and NGO facilities) increased 6.2 fold from 114 to 708. In 2009 the total number of persons treated at PEPFAR-supported NGO facilities was 43,577 versus 501,089 persons at PEPFAR-supported government facilities. Overall, the median number of patients receiving ART per site increased from 81 in 2005 to 136 in 2009.</p> <p>Conclusions</p> <p>To mitigate the gap between those needing and those receiving ART, more facilities were supported. The proportion of government facilities supported and the median number of persons treated at these facilities increased. This shift could potentially be sustainable as government sites reach more individuals and receive government funding. These results demonstrate that PEPFAR was able to support a massive scale-up of ART services in a short period of time.</p

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

Developing GIS-based eastern equine encephalitis vector-host models in Tuskegee, Alabama

<p>Abstract</p> <p>Background</p> <p>A site near Tuskegee, Alabama was examined for vector-host activities of eastern equine encephalomyelitis virus (EEEV). Land cover maps of the study site were created in ArcInfo 9.2^®from QuickBird data encompassing visible and near-infrared (NIR) band information (0.45 to 0.72 μm) acquired July 15, 2008. Georeferenced mosquito and bird sampling sites, and their associated land cover attributes from the study site, were overlaid onto the satellite data. SAS 9.1.4^®was used to explore univariate statistics and to generate regression models using the field and remote-sampled mosquito and bird data. Regression models indicated that <it>Culex erracticus </it>and Northern Cardinals were the most abundant mosquito and bird species, respectively. Spatial linear prediction models were then generated in Geostatistical Analyst Extension of ArcGIS 9.2^®. Additionally, a model of the study site was generated, based on a Digital Elevation Model (DEM), using ArcScene extension of ArcGIS 9.2^®.</p> <p>Results</p> <p>For total mosquito count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 5.041 km, nugget of 6.325 km, lag size of 7.076 km, and range of 31.43 km, using 12 lags. For total adult <it>Cx. erracticus </it>count, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 5.764 km, nugget of 6.114 km, lag size of 7.472 km, and range of 32.62 km, using 12 lags. For the total bird count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 4.998 km, nugget of 5.413 km, lag size of 7.549 km and range of 35.27 km, using 12 lags. For the Northern Cardinal count data, a first-order trend ordinary kriging process was fitted to the semivariogram at a partial sill of 6.387 km, nugget of 5.935 km, lag size of 8.549 km and a range of 41.38 km, using 12 lags. Results of the DEM analyses indicated a statistically significant inverse linear relationship between total sampled mosquito data and elevation (R²= -.4262; p < .0001), with a standard deviation (SD) of 10.46, and total sampled bird data and elevation (R²= -.5111; p < .0001), with a SD of 22.97. DEM statistics also indicated a significant inverse linear relationship between total sampled <it>Cx. erracticus </it>data and elevation (R²= -.4711; p < .0001), with a SD of 11.16, and the total sampled Northern Cardinal data and elevation (R²= -.5831; p < .0001), SD of 11.42.</p> <p>Conclusion</p> <p>These data demonstrate that GIS/remote sensing models and spatial statistics can capture space-varying functional relationships between field-sampled mosquito and bird parameters for determining risk for EEEV transmission.</p

Differential protein profiling as a potential multi-marker approach for TSE diagnosis

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177This "proof of concept" study, examines the use of differential protein expression profiling using surface enhanced laser desorption and ionisationtime of flight mass spectrometry (SELDI-TOF) for the diagnosis of TSE disease. Spectral output from all proteins selectively captured from individual murine brain homogenate samples, are compared as "profiles" in groups of infected and non-infected animals. Differential protein expression between groups is thus highlighted and statistically significant protein "peaks" used to construct a panel of disease specific markers. Studies at both terminal stages of disease and throughout the time course of disease have shown a disease specific protein profile or "disease fingerprint" which could be used to distinguish between groups of TSE infected and uninfected animals at an early time point of disease. Results Our results show many differentially expressed proteins in diseased and control animals, some at early stages of disease. Three proteins identified by SELDI-TOF analysis were verified by immunohistochemistry in brain tissue sections. We demonstrate that by combining the most statistically significant changes in expression, a panel of markers can be constructed that can distinguish between TSE diseased and normal animals. Conclusion Differential protein expression profiling has the potential to be used for the detection of disease in TSE infected animals. Having established that a "training set" of potential markers can be constructed, more work would be required to further test the specificity and sensitivity of the assay in a "testing set". Based on these promising results, further studies are being performed using blood samples from infected sheep to assess the potential use of SELDI-TOF as a pre-mortem blood based diagnostic.https://doi.org/10.1186/1471-2334-9-1889pubpub

Erratum: Oral salt and water versus intravenous saline for the prevention of acute kidney injury following contrast-enhanced computed tomography: study protocol for a pilot randomized trial Salmonella blood stream infections in a tertiary care setting in Ghana.

[This corrects the article DOI: 10.1186/s40697-015-0048-7.]

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

QTL analysis for resistance to foliar damage caused by Thrips tabaci and Frankliniella schultzei (Thysanoptera: Thripidae) feeding in cowpea [Vigna unguiculata (L.) Walp.]

Three quantitative trait loci (QTL) for resistance to Thrips tabaci and Frankliniella schultzei were identified using a cowpea recombinant inbred population of 127 F2:8 lines. An amplified fragment length polymorphism (AFLP) genetic linkage map and foliar feeding damage ratings were used to identify genomic regions contributing toward resistance to thrips damage. Based on Pearson correlation analysis, damage ratings were highly correlated (r ≥ 0.7463) across seven field experiments conducted in 2006, 2007, and 2008. Using the Kruskall–Wallis and Multiple-QTL model mapping packages of MapQTL 4.0 software, three QTL, Thr-1, Thr-2, and Thr-3, were identified on linkage groups 5 and 7 accounting for between 9.1 and 32.1% of the phenotypic variance. AFLP markers ACC-CAT7, ACG-CTC5, and AGG-CAT1 co-located with QTL peaks for Thr-1, Thr-2, and Thr-3, respectively. Results of this study will provide a resource for molecular marker development and the genetic characterization of foliar thrips resistance in cowpea

Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis