Potential role of embelin in the prevention of Freund's adjuvant induced inflammation and ROS.

Inflammation is a complex biological response involving immune cells to an infection creating injury to the normal tissues. The anti-inflammatory efficacy of embelin, a benzoquinone from the plant Embelia ribes, was screened for antioxidant and anti-inflammatory activity in carrageenan and Freund's adjuvant-induced inflammation models. Embelin exhibited significant dose-dependent antioxidant potential. In carrageenan-induced inflammation, embelin (20 mg/kg) showed an inhibition of oedema by 71.01 ± 0.12% and 81.91 ± 0.67% in Freund's adjuvant-treated chronic inflammation model and resulted in a noticeable increase in adrenal size and restoration of the weight of spleen. Embelin also demonstrated cytoprotective effects on HEK-293 cells under induced oxidative stress. In silico analysis, embelin demonstrated binding energy of - 7.7 kcal/Mol and - 7.0 kcal/Mol with COX1 and COX2 with two hydrogen bonds. These results further prove that embelin could be a promising anti-inflammatory agent and supports the traditional use of Embelia ribes for rheumatism.

Carbon dots derived from Beta vulgaris: evaluation of its potential as antioxidant and anticancer agent.

Carbon dots (CDs) endowed with outstanding physico-chemical characteristics expeditiously garnered tremendous popularity in the scientific community. CDs can be synthesized from a variety of natural resources and can replace metal semiconductor quantum dots in the range of applications such as bio-imaging, sensing and catalysis. Herein, CDs are green synthesized fromBeta vulgarisvia a single step hydrothermal approach (b-CDs). The synthesized carbon dots are characterized using UV-visible spectrophotometry, Fluorescence spectroscopy, High resolution transmission electron microscopy (HR-TEM), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction technique (XRD) and Raman spectroscopy. The b-CDs hence developed exhibited the signature 'excitation-dependent fluorescence emission' with its most intense emission in the green region. The quantum yield for the b-CDs obtained by this synthetic approach evinced an appreciable value of 11.6%. The antioxidant property of b-CDs are evaluated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay to obtain a maximum scavenging activity of 94.5% at a concentration of 1000µg ml-1and its underlying mechanisms are illustrated. The blood compatibility of b-CDs are assessed using haemolysis assay and the cytotoxicity evaluated using MTT assay shows significant cell growth-inhibition against the human breast cancer (MCF-7) and hepatocellular carcinoma (HepG2) cell lines. This succinct study demonstrates the inherent therapeutic potential of biocompatible carbon dots.

Automated motif discovery from glycan array data.

Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface ( http://glycanmotifminer.emory.edu ). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs.

Digital Pathology: Data-Intensive Frontier in Medical Imaging: Health-information sharing, specifically of digital pathology, is the subject of this paper which discusses how sharing the rich images in pathology can stretch the capabilities of all otherwise well-practiced disciplines.

Pathology is a medical subspecialty that practices the diagnosis of disease. Microscopic examination of tissue reveals information enabling the pathologist to render accurate diagnoses and to guide therapy. The basic process by which anatomic pathologists render diagnoses has remained relatively unchanged over the last century, yet advances in information technology now offer significant opportunities in image-based diagnostic and research applications. Pathology has lagged behind other healthcare practices such as radiology where digital adoption is widespread. As devices that generate whole slide images become more practical and affordable, practices will increasingly adopt this technology and eventually produce an explosion of data that will quickly eclipse the already vast quantities of radiology imaging data. These advances are accompanied by significant challenges for data management and storage, but they also introduce new opportunities to improve patient care by streamlining and standardizing diagnostic approaches and uncovering disease mechanisms. Computer-based image analysis is already available in commercial diagnostic systems, but further advances in image analysis algorithms are warranted in order to fully realize the benefits of digital pathology in medical discovery and patient care. In coming decades, pathology image analysis will extend beyond the streamlining of diagnostic workflows and minimizing interobserver variability and will begin to provide diagnostic assistance, identify therapeutic targets, and predict patient outcomes and therapeutic responses.

The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas.

The Cancer Genome Atlas Project (TCGA) has produced an extensive collection of '-omic' data on glioblastoma (GBM), resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt), which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium's expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6), but also among 75 grade II and grade III samples (p  =  2.65e-4). This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n =  43, p  =  1.25e-4). Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy.

An integrative approach for in silico glioma research.

The integration of imaging and genomic data is critical to forming a better understanding of disease. Large public datasets, such as The Cancer Genome Atlas, present a unique opportunity to integrate these complementary data types for in silico scientific research. In this letter, we focus on the aspect of pathology image analysis and illustrate the challenges associated with analyzing and integrating large-scale image datasets with molecular characterizations. We present an example study of diffuse glioma brain tumors, where the morphometric analysis of 81 million nuclei is integrated with clinically relevant transcriptomic and genomic characterizations of glioblastoma tumors. The preliminary results demonstrate the potential of combining morphometric and molecular characterizations for in silico research.

In patients coming to theatre with an intra aortic balloon pump, is it better to turn it off or keep it on while on bypass?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In patients coming to theatre with an intra aortic balloon pump (IABP), is it better to turn it off or keep it on while on bypass?' Altogether 46 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. Nine of them were randomised controlled trials (RCTs). The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The different RCTs were performed looking at various effects of IABP induced pulsatility during cardiopulmonary bypass (CPB) and cardioplegic arrest. These studies showed that IABP induced pulsatile perfusion results in improved perfusion to vital organs, better lung function in chronic obstructive pulmonary disease patients, ameliorates the coagulative system and lowers endothelial activation. Despite these facts a survey in the UK and Ireland showed that 80.5% of cardiac surgeons stop IABP on commencing CPB. We conclude that in patients who already have IABP in-situ whilst going on CPB there is enough evidence in the literature to suggest that it should be turned on to internal trigger mode. Although several randomised control trials in this field have conveyed considerable benefit in terms of biochemical markers measured, none of them have resulted in better clinical outcomes in terms of reduction in major morbidity or mortality. This may be largely due to the small sample size in most of these studies. Seven out of 11 papers were published by same group of authors.

Wound healing and protease inhibition activity of Bacoside-A, isolated from Bacopa monnieri wettest.

Bacopa monnieri (L.) Wettest. (Scrophulariaceae) is a well-known medicinal herb. In the Indian system of medicine it is known as Brahmi (Sanskrit) and Indian water hyssop. Methanolic extract of Bacopa monnieri and its isolated constituent Bacoside-A were screened for wound healing activity. Bacoside-A was screened for wound healing activity by excision, incision and dead space wound on Swiss albino rats. Significant wound healing activity was observed in both extract and the Bacoside-A treated groups. The SDS-PAGE caseinolytic zymogram analysis of inhibition of matrix metalloproteases (MMPs) enzyme from the excision wound by Bacoside-A, an isolated constituent, was done with the concentrations 100 and 200 micromg/ml. In Bacoside-A treated groups, epithelialization of the excision wound was faster with a high rate (18.30 +/- 0.01 days) of wound contraction. The tensile strength of the incision wound was increased (538.47 +/- 0.14 g) in the Bacoside-A treated group. In the dead space wound model, the weight of the granuloma was also increased (89.15 +/- 0.08 g). The histological examination of the granuloma tissue of the Bacoside-A treated group showed increased cross-linking of collagen fibers and absence of monocytes. The wound healing activity of Bacoside-A was more effective in various wound models compared to the standard skin ointment Nitrofurazone.

Inpatient Oral Anticoagulation Management by Clinical Pharmacists: Safety and Cost effectiveness.

BACKGROUND: Warfarin prescription for anticoagulation after cardiac surgery has always been a challenge for junior medical staff. METHODS: A prospective study was carried out to assess the quality of anticoagulation control by junior doctors compared with clinical pharmacists at South Manchester University hospitals NHS Trust. The junior medical staff prescribed warfarin for 50 consecutive patients from April to September 2006 (group A, n = 50) and experienced clinical pharmacists dosed 46 consecutive patients between February and May 2007 (group B, n = 46). RESULTS: In group A, 9 (18%) patients discharge was delayed because of lack of attainment of therapeutic International Normalised Ratio (INR) compared to 3 (6.5%) in group B. The total number of bed days resulting from the delay in group A was 21 compared to 4 in group B. Extrapolated over a year this would amount to approximately 15,750 extra cost incurred in group A opposed to 3000 in group B. CONCLUSIONS: The pharmacists were significantly better than junior doctors in achieving therapeutic INR, resulting in fewer discharge delays. The clinical pharmacists with experience in outpatient anticoagulation clinic can play an important role in inpatient oral anticoagulation management in post cardiac surgery patients thereby providing improved cost effective quality of care. KEYWORDS: Warfarin; Pharmacist; Management.

Localized content-based image retrieval.

We define localized content-based image retrieval as a CBIR task where the user is only interested in a portion of the image, and the rest of the image is irrelevant. In this paper we present a localized CBIR system, Accio, that uses labeled images in conjunction with a multiple-instance learning algorithm to first identify the desired object and weight the features accordingly, and then to rank images in the database using a similarity measure that is based upon only the relevant portions of the image. A challenge for localized CBIR is how to represent the image to capture the content. We present and compare two novel image representations, which extend traditional segmentation-based and salient point-based techniques respectively, to capture content in a localized CBIR setting.

Wound healing activity and docking of glycogen-synthase-kinase-3-beta-protein with isolated triterpenoid lupeol in rats.

A triterpene compound lupeol isolated from petroleum ether extract of leaves of Celastrus paniculatus was screened for wound healing activity (8 mg/ml of 0.2% sodium alginate gel) by excision, incision and dead space wound models on Swiss Albino rats (175-225 g). In lupeol treated groups wound healing activity was more significant (17.83+/-0.48) than the standard skin ointment nitrofurazone (18.33+/-0.42). Epithelialization of the incision wound was faster with a high rate of wound contraction (571.50+/-5.07) as compared with the control group. In dead space wound model also the weight of the granulation tissue of the lupeol treated animal was increased indicating increase of collagenation and absence of monocytes. The comparative docking of isolated lupeol molecule and standard drug nitrofurazone to glycogen synthase kinase 3-beta protein by Wnt signaling pathway also supported the wound healing property of lupeol. The activation domain of GSK3-beta consisted of Tyr216, with residues Asn64, Gly65, Ser66, Phe67, Gly68, Val70, Lys85, Leu132, Val135, Asp181 in the active pocket docked with lupeol at the torsional degree of freedom 0.5 units with Lamarckian genetic algorithm showed the inhibition constant of 1.38 x 10(-7). The inhibition constant of nitrofurazone was only 1.35 x 10(-4).