Risk assessment of Pakistani individuals for diabetes (RAPID)

ObjectiveTo develop and evaluate a risk score to predict people at high risk of developing type 2 diabetes in Pakistan.MethodologyCross sectional data regarding primary prevention of diabetes in Pakistan. Diabetes risk score was developed by using simple parameters namely age, waist circumference, and family history of diabetes. Odds ratios of the model were used to assign a score value for each variable and the diabetes risk score was calculated as the sum of those scores.ResultsWe externally validated the score using two data from 1264 subjects and 856 subjects aged 25 years and above from two separate studies respectively. Validating this score using the first data from the second screening study gave an area under the receive operator characteristics curve [AROC] of 0.758. A cut point of 4 had a sensitivity of 47.0% and specificity of 88% and in the second data AROC is 0.7 with 44% sensitivity and 89% specificity.ConclusionsA simple diabetes risk score, based on a set of variables can be used for the identification of high risk individuals for early intervention to delay or prevent type 2 diabetes in Pakistani population.     

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT.     

Saikosaponins: a review of pharmacological effects

Over the past decades, a number of phytochemicals have been reported to possess potent pharmacological effects. Saikosaponins represent a group of oleanane derivatives, usually as glucosides, which are commonly found in medicinal plants Bupleurum spp., which have been used as traditional Chinese medicine for more than 1,000 years in China. Emerging evidence suggests that saikosaponins have many pharmacological effects, including sedation, anticonvulsant, antipyretic, antiviral, immunity, anti-inflammation, antitumor properties, protecting liver and kidney and so on. The present review provides a comprehensive summary and analysis of the pharmacological properties of saikosaponins, supporting the potential uses of saikosaponins as a medicinal agent.     

Similarity-Dissimilarity Plot for Visualization of High Dimensional Data in Biomedical Pattern Classification

In pattern classification problems, feature extraction is an important step. Quality of features in discriminating different classes plays an important role in pattern classification problems. In real life, pattern classification may require high dimensional feature space and it is impossible to visualize the feature space if the dimension of feature space is greater than four. In this paper, we have proposed a Similarity-Dissimilarity plot which can project high dimensional space to a two dimensional space while retaining important characteristics required to assess the discrimination quality of the features. Similarity-dissimilarity plot can reveal information about the amount of overlap of features of different classes. Separable data points of different classes will also be visible on the plot which can be classified correctly using appropriate classifier. Hence, approximate classification accuracy can be predicted. Moreover, it is possible to know about whom class the misclassified data points will be confused by the classifier. Outlier data points can also be located on the similarity-dissimilarity plot. Various examples of synthetic data are used to highlight important characteristics of the proposed plot. Some real life examples from biomedical data are also used for the analysis. The proposed plot is independent of number of dimensions of the feature space.     

Non-invasive Evaluation of Right Ventricular Function with Real-Time 3-D Echocardiography

The aim of this study was to evaluate the accuracy and feasibility of real-time 3-D echocardiography (3-DE) in assessing right ventricular (RV) systolic function. A latex balloon was inserted into the right ventricle of 20 freshly harvested pig hearts which were then passively driven by a pulsatile pump apparatus. The RV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and RV ejection fraction (RVEF), derived from 3-DE, as well as the RVEF obtained from 2-D echocardiography (2-DE) were quantified at different stroke volumes (30–70 mL) and compared with sonomicrometry data. In all comparisons, 3-D GLS, GCS, GAS, 2-D RVEF and 3-D RVEF exhibited strong correlations with sonomicrometry data (r = 0.89, 0.79, 0.74, 0.80, and 0.93, respectively; all p values < 0.001). Bland–Altman analyses revealed slight overestimations of echo-derived GLS, GCS, 2-DE RVEF and 3-DE RVEF compared with sonomicrometry values (bias = 1.55, 2.72, 3.59 and 2.21, respectively). Furthermore, there is better agreement among GLS, 3-D RVEF and the sonomicrometry values than between GCS and 2-D RVEF. Real-time 3-DE is more feasible and accurate for assessing RV function than 2-DE. GLS is a potential alternative parameter for quantifying RV systolic function.