Taxol-DNA interactions: fluorescence and CD studies of DNA groove binding properties of taxol

Taxol is perhaps the most successful drug used for the treatment of various cancers. Comprehensive literature accumulated on therapeutics of the drug has indicated numerous side effects. In this paper, by use of fluorescence spectroscopy, it is shown that taxol binds to DNA with an affinity constant (Ka) of 1.08×107 M-1. This binding is accompanied by a large 'red edge excitation shift' (REES) of fluorescence emission maximum in taxol-DNA complex. The results point to an interaction of taxol with its core eight-membered ring in the DNA groove and the three phenyl rings projecting away from the DNA. The drug encompasses about two base pairs of DNA upon binding to it. Systematic studies with taxol analogues confirms such a mode of binding. These interesting findings on hitherto unknown taxol-DNA interactions may have clinical implications in view of its large number of side effects and pharmacokinetics

School environment assessment tools to address behavioural risk factors of non-communicable diseases: A scoping review

We aimed to identify, describe and analyse school environment assessment (SEA) tools that address behavioural risk factors (unhealthy diet, physical inactivity, tobacco and alcohol consumption) for non-communicable diseases (NCD). We searched in MEDLINE and Web of Science, hand-searched reference lists and contacted experts. Basic characteristics, measures assessed and measurement properties (validity, reliability, usability) of identified tools were extracted. We narratively synthesized the data and used content analysis to develop a list of measures used in the SEA tools. Twenty-four SEA tools were identified, mostly from developed countries. Out of these, 15 were questionnaire based, 8 were checklists or observation based tools and one tool used a combined checklist/observation based and telephonic questionnaire approach. Only 1 SEA tool had components related to all the four NCD risk factors, 2 SEA tools has assessed three NCD risk factors (diet/nutrition, physical activity, tobacco), 10 SEA tools has assessed two NCD risk factors (diet/nutrition and physical activity) and 11 SEA tools has assessed only one of the NCD risk factor. Several measures were used in the tools to assess the four NCD risk factors, but tobacco and alcohol was sparingly included. Measurement properties were reported for 14 tools. The review provides a comprehensive list of measures used in SEA tools which could be a valuable resource to guide future development of such tools. A valid and reliable SEA tool which could simultaneously evaluate all NCD risk factors, that has been tested in different settings with varying resource availability is needed

Epitope-Based Immunoinformatics and Molecular Docking Studies of Nucleocapsid Protein and Ovarian Tumor Domain of Crimean–Congo Hemorrhagic Fever Virus

Crimean–Congo hemorrhagic fever virus (CCHFV), the fatal human pathogen is transmitted to humans by tick bite, or exposure to infected blood or tissues of infected livestock. The CCHFV genome consists of three RNA segments namely, S, M, and L. The unusual large viral L protein has an ovarian tumor (OTU) protease domain located in the N terminus. It is likely that the protein may be autoproteolytically cleaved to generate the active virus L polymerase with additional functions. Identification of the epitope regions of the virus is important for the diagnosis, phylogeny studies, and drug discovery. Early diagnosis and treatment of CCHF infection is critical to the survival of patients and the control of the disease. In this study, we undertook different in silico approaches using molecular docking and immunoinformatics tools to predict epitopes which can be helpful for vaccine designing. Small molecule ligands against OTU domain and protein–protein interaction between a viral and a host protein have been studied using docking tools

Aid conditionalities, international Good Manufacturing Practice standards and local production rights: a case study of local production in Nepal

© 2015 Brhlikova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This work was supported by the Economic and Social Research Council and the Department for International Development [RES-167-25-0110] through the collaborative research project Tracing Pharmaceuticals in South Asia (2006 – 2009). In addition to the authors of this paper, the project team included: Soumita Basu, Gitanjali Priti Bhatia, Erin Court, Abhijit Das, Stefan Ecks, Patricia Jeffery, Roger Jeffery, Rachel Manners, and Liz Richardson. Martin Chautari (Kathmandu) and the Centre for Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper but are not responsible for the views expressed, nor are ESRC or DFID. Ethical review was provided by the School of Social and Political Science at the University of Edinburgh, and ethical approval in Nepal for the study granted by the Nepal Health Research Council (NHRC)

Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial.

BACKGROUND: Optimal postoperative pain management is important to ensure patient comfort and early mobilization. METHODS: In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients \u3e=18 years of age who had pain at rest \u3e=5 (0--10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1--3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1--3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated. RESULTS: The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1--3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p \u3c 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1--3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p \u3c 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. CONCLUSIONS: Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption.Clinical trial registration: NCT00820027

Preferences and skills of Indian public sector teachers

With a sample of 700 future public sector primary teachers in India, a Discrete Choice Experiment is used to measure job preferences, particularly regarding location. General skills are also tested. Urban origin teachers and women are more averse to remote locations than rural origin teachers and men respectively. Women would require a 26-73 percent increase in salary for moving to a remote location. The results suggest that existing caste and gender quotas can be detrimental for hiring skilled teachers willing to work in remote locations. The most preferred location is home, which supports decentralised hiring, although this could compromise skills

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis