Treatment of gastrointestinal stromal tumor: focus on imatinib mesylate

Gastrointestinal stromal tumor (GIST) is a rare primary neoplasm of the gastrointestinal tract, mesentery, or omentum. In the past, surgery has been the only effective treatment. The diagnosis and treatment of GIST has been revolutionized over the past decade, since expression of the receptor tyrosine kinase KIT was shown to occur on these tumors. Mutations in this proto-oncogene commonly cause constitutive activation of the KIT tyrosine kinase receptor, an important factor in the pathogenesis of the disease. The development of specific tyrosine kinase inhibitors, such as imatinib mesylate, has led to a breakthrough in the treatment of advanced GIST. Treatment with this drug has led to significant improvements in survival, with overall response rates in excess of 80%. Side effects are common, but usually manageable. The success of this drug has led to further trials investigating its use in the pre- and postoperative situation. This review summarizes the current knowledge of GIST and imatinib treatment and possible future developments

TaqMan real-time PCR assay for relative quantitation of white spot syndrome virus infection in Penaeus monodon Fabricius exposed to ammonia.

White spot disease is caused by a highly virulent pathogen, the white spot syndrome virus (WSSV). The disease is usually triggered by changes in environmental parameters causing severe losses to the shrimp industry. This study was undertaken to quantify the relative WSSV load in shrimp exposed to ammonia, using a TaqMan-based real-time PCR, and their subsequent susceptibility to WSSV. Shrimp were exposed to different levels of total ammonia nitrogen (TAN) (8.1, 3.8 and 1.1 mg L−1) for 10 days and challenged with WSSV by feeding WSSV-positive shrimp. WSSV was detected simultaneously in haemolymph, gills and pereopods at four hours post-infection. The TaqMan real-time PCR assay showed a highly dynamic detection limit that spanned over 6 log10 concentrations of DNA and high reproducibility (standard deviation 0.33–1.42) and small correlation of variability (CV) (1.89–3.85%). Shrimp exposed to ammonia had significantly higher (P < 0.01) WSSV load compared to the positive control, which was not exposed to ammonia. Shrimp exposed to 8.1 mg L−1 of TAN had the highest (P < 0.01) WSSV load in all three organs in comparison with those exposed to 3.8 and 1.1 mg L−1 of TAN. However, haemolymph had significantly higher (P < 0.01) viral load compared to the gills and pereopods. Results showed that shrimp exposed to ammonia levels as low as 1.1 mg L−1 (TAN) had increased susceptibility to WSSV

The presence of geophysical loadings in gps observations using general least squares approaches

The earth's crust undergoes natural deformation due to the geophysical loadings that consist of the earth body tide, ocean tide loading, atmospheric pressure loading and pole tide. This periodic displacement is generated by the changes of the gravitational attraction between the moon and the sun acting upon the earth's rotation, along with the temporal atmospheric changes and the variability of the ocean tide. The study of the geophysical loadings is important in the geodesy field as the magnitude of the signals is significant and can contribute to errors in space geodetic measurements such as Global Positioning System (GPS), Very-Long Baseline Interferometry (VLBI) and Altimeter. This study is conducted to evaluate the percentage of geophysical loadings in GPS observations by adopting general least square approaches. The presence of the geophysical loadings indicates that as many as 76% to 93% of the geophysical loadings signal are contained in the GPS time series. The findings reveal that earth body tide signals are more significant if compared to ocean tide loading signals because the magnitude of the earth body tide is greater than that of the ocean tide loading and it affects the coordinate system particularly at up component. Results illustrated the potential of GPS to provide the local parameters of the geophysical loadings that are beneficial for earth tidal modelling and that can be used to improve the quality of space geodetic measurements

The challenge of measuring physical activity

Measuring physical activity accurately and reliably is essential when physical activity is either an intervention or an outcome measure. Measurement of physical activity in population groups has been undertaken in a number of ways, including self-report, observation, heart rate measurement and activity monitors. The strengths and weaknesses of each of these methods will be reviewed. The measurement of physical activity in children is an additional challenge and data from the recently completed pilot study of the Kajian Aktiviti Fizikal dan Sukan Pelajar Sekolah Malaysia 2008 (KAFS08) will be used to illustrate these complexities. Questionnaire and activity monitoring data were collected from 163 children attending four schools in Kuala Lumpur with an age range of 9-18 years. Three models of activity monitors were used (YAMAX SW-700, OMRON HJ113, ACTIGRAPH GT1M) and on completion of data collection, significant differences were found between pedometer steps recorded on each monitor, after allowing for age and gender differences. A subsequent study on the differences between the three monitors was undertaken involving over 15 individuals and over 40 days of measurement where one individual wore each of the three monitors for a full day. In addition, the accuracy of each monitor was determined by comparing the step count registered by the monitor with actual number of steps counted

Low Birth Weight Prediction Using JNN

Abstract: In this research, an Artificial Neural Network (ANN) model was developed and tested to predict Birth Weight. A number of factors were identified that may affect birth weight. Factors such as smoke, race, age, weight (lbs) at last menstrual period, hypertension, uterine irritability, number of physician visits in 1st trimester, among others, as input variables for the ANN model. A model based on multi-layer concept topology was developed and trained using the data from some birth cases in hospitals. The evaluation of testing the dataset shows that the ANN model is capable of correctly predicting the birth weight with 100% accuracy

An integrated priority-based cell attenuation model for dynamic cell sizing

A new, robust integrated priority-based cell attenuation model for dynamic cell sizing is proposed and simulated using real mobile traffic data.The proposed model is an integration of two main components; the modified virtual community – parallel genetic algorithm (VC-PGA) cell priority selection module and the evolving fuzzy neural network (EFuNN) mobile traffic prediction module.The VC-PGA module controls the number of cell attenuations by ordering the priority for the attenuation of all cells based on the level of mobile level of mobile traffic within each cell.The EFuNN module predicts the traffic volume of a particular cell by extracting and inserting meaningful rules through incremental, supervised real-time learning.The EFuNN module is placed in each cell and the output, the predicted mobile traffic volume of the particular cell, is sent to local and virtual community servers in the VC-PGA module.The VC-PGA module then assigns priorities for the size attenuation of all cells within the network, based on the predicted mobile traffic levels from the EFuNN module at each cell.The performance of the proposed module was evaluated on five adjacent cells in Selangor, Malaysia. Real-time predicted mobile traffic from the EFuNN structure was used to control the size of all the cells.Results obtained demonstrate the robustness of the integrated module in recognizing the temporal pattern of the mobile traffic and dynamically controlling the cell size in order to reduce the number of calls dropped

Synchronized cycles of bacterial lysis for in vivo delivery

The pervasive view of bacteria as strictly pathogenic has given way to an ppreciation of the widespread prevalence of beneficial microbes within the human body. Given this milieu, it is perhaps inevitable that some bacteria would evolve to preferentially grow in environments that harbor disease and thus provide a natural platform for the development of engineered therapies. Such therapies could benefit from bacteria that are programmed to limit bacterial growth while continually producing and releasing cytotoxic agents in situ. Here, we engineer a clinically relevant bacterium to lyse synchronously at a threshold population density and to release genetically encoded cargo. Following quorum lysis, a small number of surviving bacteria reseed the growing population, thus leading to pulsatile delivery cycles. We use microfluidic devices to characterize the engineered lysis strain and we demonstrate its potential as a drug deliver platform via co-culture with human cancer cells in vitro. As a proof of principle, we track the bacterial population dynamics in ectopic syngeneic colorectal tumors in mice. The lysis strain exhibits pulsatile population dynamics in vivo, with mean bacterial luminescence that remained two orders of magnitude lower than an unmodified strain. Finally, guided by previous findings that certain bacteria can enhance the efficacy of standard therapies, we orally administer the lysis strain, alone or in combination with a clinical chemotherapeutic, to a syngeneic transplantation model of hepatic colorectal metastases. We find that the combination of both circuit-engineered bacteria and chemotherapy leads to a notable reduction of tumor activity along with a marked survival benefit over either therapy alone. Our approach establishes a methodology for leveraging the tools of synthetic biology to exploit the natural propensity for certain bacteria to colonize disease sites.National Institute of General Medical Sciences (U.S.) (GM069811)San Diego Center for Systems Biology (P50 GM085764)National Cancer Institute (U.S.). Swanson Biotechnology Center (Koch Institute Support Grant (P30-CA14051))National Institute of Environmental Health Sciences (Core Center Grant (P30- ES002109))National Institutes of Health (U.S.) (NIH Pathway to Independence Award NIH (K99 CA197649-01))Misrock Postdoctoral fellowshipNational Defense Science and Engineering Graduate (NDSEG) Fellowshi

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Spectrophotometric determination of tizanidine and orphenadrine via ion pair complex formation using eosin Y

A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of two skeletal muscle relaxants namely, tizanidine hydrochloride (I) and orphenadrine citrate (II) in pharmaceutical formulations. The proposed method is based on the formation of a binary complex between the studied drugs and eosin Y in aqueous buffered medium (pH 3.5). Under the optimum conditions, the binary complex showed absorption maxima at 545 nm for tizanidine and 542 nm for orphenadrine. The calibration plots were rectilinear over concentration range of 0.5-8 μg/mL and 1-12 μg/mL with limits of detection of 0.1 μg/mL and 0.3 μg/mL for tizanidine and orphenadrine respectively. The different experimental parameters affecting the development and stability of the complex were studied and optimized. The method was successfully applied for determination of the studied drugs in their dosage forms; and to the content uniformity test of tizanidine in tablets