Combined effects of a third-generation bisphosphonate, zoledronic acid with other anticancer agents against murine osteosarcoma

Bisphosphonates (BPs) are widely used to treat bone diseases and also appear to possess direct antitumour activity. We have previously reported that third-generation BPs such as zoledronic acid (ZOL) and minodronic acid (YM529) synergistically augment the effects of anticancer agents in various cancer cells. Recently, we have also reported the antitumour effects of YM529 on murine osteosarcoma cells. As YM529 has not been clinically available, we herein focused on the anti-osteosarcoma effects of ZOL which is clinically available. In addition to ZOL alone, we evaluated the concurrent or sequential combined effects of ZOL with other anticancer agents against murine osteosarcoma cell lines. ZOL showed almost same anti-osteosarcoma activity compared with YM529 and more sensitive growth inhibitory effects against osteosarcoma cells than normal cells. Moreover, ZOL acted synergistically in vitro when administered concurrently with paclitaxel (PAC) or gemcitabine (GEM), not only in wild-type osteosarcoma cells but also in P-glycoprotein (P-gp)-overexpressing osteosarcoma cells, which were much less sensitive against each anticancer agent. Furthermore, 24 h of ZOL pretreatment significantly augmented the sensitivity of doxorubicin (DOX), PAC or GEM against osteosarcoma cells. These findings suggest that combined administration of ZOL with other anticancer agents may improve the osteosarcoma treatment

The Gene Ontology resource: enriching a GOld mine

The Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding the functions of genes and gene products. Here, we report the advances of the consortium over the past two years. The new GO-CAM annotation framework was notably improved, and we formalized the model with a computational schema to check and validate the rapidly increasing repository of 2838 GO-CAMs. In addition, we describe the impacts of several collaborations to refine GO and report a 10% increase in the number of GO annotations, a 25% increase in annotated gene products, and over 9,400 new scientific articles annotated. As the project matures, we continue our efforts to review older annotations in light of newer findings, and, to maintain consistency with other ontologies. As a result, 20 000 annotations derived from experimental data were reviewed, corresponding to 2.5% of experimental GO annotations. The website (http://geneontology.org) was redesigned for quick access to documentation, downloads and tools. To maintain an accurate resource and support traceability and reproducibility, we have made available a historical archive covering the past 15 years of GO data with a consistent format and file structure for both the ontology and annotations

An overview of geospatial methods used in unintentional injury epidemiology

BACKGROUND: Injuries are a leading cause of death and disability around the world. Injury incidence is often associated with socio-economic and physical environmental factors. The application of geospatial methods has been recognised as important to gain greater understanding of the complex nature of injury and the associated diverse range of geographically-diverse risk factors. Therefore, the aim of this paper is to provide an overview of geospatial methods applied in unintentional injury epidemiological studies. METHODS: Nine electronic databases were searched for papers published in 2000-2015, inclusive. Included were papers reporting unintentional injuries using geospatial methods for one or more categories of spatial epidemiological methods (mapping; clustering/cluster detection; and ecological analysis). Results describe the included injury cause categories, types of data and details relating to the applied geospatial methods. RESULTS: From over 6,000 articles, 67 studies met all inclusion criteria. The major categories of injury data reported with geospatial methods were road traffic (n = 36), falls (n = 11), burns (n = 9), drowning (n = 4), and others (n = 7). Grouped by categories, mapping was the most frequently used method, with 62 (93%) studies applying this approach independently or in conjunction with other geospatial methods. Clustering/cluster detection methods were less common, applied in 27 (40%) studies. Three studies (4%) applied spatial regression methods (one study using a conditional autoregressive model and two studies using geographically weighted regression) to examine the relationship between injury incidence (drowning, road deaths) with aggregated data in relation to explanatory factors (socio-economic and environmental). CONCLUSION: The number of studies using geospatial methods to investigate unintentional injuries has increased over recent years. While the majority of studies have focused on road traffic injuries, other injury cause categories, particularly falls and burns, have also demonstrated the application of these methods. Geospatial investigations of injury have largely been limited to mapping of data to visualise spatial structures. Use of more sophisticated approaches will help to understand a broader range of spatial risk factors, which remain under-explored when using traditional epidemiological approaches

Access recirculation and adequacy of hemodialysis in different types of vascular access

Introduction: Haemodialysis requires recirculation, and it happens when dialysed blood returning through the venous needle re-enters the extracorporeal circuit through the arterial needle, rather than returning to the systemic circulation. Significant recirculation should be expected, when there is an inadequate reduction in the values of urea. During End-Stage Renal Disease (ESRD), adequate dialysis is of utmost importance because it influences the morbidity and mortality of the patients. Methods and materials: The study was carried out in 200 patients who underwent haemodialysis at the dialysis unit in Kalyani kidney care centre, Erode. Patients were actively evaluated from February 2018 till November 2018. Patients were randomized and accordingly 64 patients were enrolled in category I Arteriovenous fistula (AVF), 63 Patients in category II Internal Jugular Catheter (IJC) and category III Femoral Catheter (FC) each and 10 patients in category IV Perm Catheter (PC). Success recirculation was estimated and adequacy of haemodialysis was done virtually. Calculated Kt/V was done in almost all patients. For assessing vascular access recirculation, the technique that was used was urea-based measurement (Two needles with three samples of blood). The recirculation percentage was calculated as(S-A)/(S-V) X100. For assessing the adequacy of haemodialysis, Kt/V was used where K is estimated from (Cbi-Cbo)/ (CbixQb), time duration of dialysis (t) and urea distribution volume (V) is determined from the Watson equations for men and women. Kt/V was also measured with Online Clearance Monitoring (OCM) in Fresenius machine 4000S. Results: The mean access recirculation rate was 6.3+5.1% in those with AVF, while in IJC and FC groups were 6.7+4.5% and 24.4+11.7% respectively. When the two groups were compared, AVF vs FC groups, the difference was statistically significant (p value<0.001) and in IJC vs FC groups, the difference was statistically less significant (p-value <0.001) in both AR% and online Kt/V. Conclusion: An arteriovenous2QQ2 fistula has less access recirculation, when compared to temporary catheters. On the other hand, the femoral catheter has more access recirculation, when compared to the internal jugular catheter. The difference in calculated Kt/V with the three types of vascular access has no statistical significance

Assessment of Wire Offset While Machining EN-24 on WEDM

Wire offset is the dimensional shift that is experienced while machining a job on Wire-EDM machine. This modeling of wire offset during machining of EN-24 (EN is Euro Norm) was performed implementing Response Surface Methodology (RSM). Factors under consideration are peak current, on duration and off duration of pulse. Scanning Electron Microscopy was later performed for measurement of dimensional shift experienced under various machining conditions. The difference of programmed width and actual width obtained revealed the wire offset of the machined specimen. The tests revealed that Wire-EDM (Wire-Electro Discharge Machine) variables and Wire Offset can be modelled using Quadratic equations. ANOVA (Analysis of Variance) depicted that quadratic term of peak current is crucial parameter for Wire offset trailed by off duration. Keeping medium level of electrical parameters will lead to lower wire offset. Further model validation was performed and the residual error for Wire Offset was found to be 2.43% which suggest the competence of the present model

EVALUATION OF HIGH STRENGTH CONCRETE USING HOSPITAL WASTE ASH AND SILICA SAND IN CONCRETE

<p><strong>Abstract</strong></p><p>Concrete is a material constituted of cement, Sand, Coarse aggregates, and water. Cement is the predominant component of both conventional and Replacement concrete. Cement processing emits massive concentrations of Carbon-dioxide throughout the environment. To reduce the concentration, cement is substitute by any local available cementitious material. Nowadays, due to the carbon dioxide and global warming, several investigations are undergoing replacement cement. Several new products are used as an effluent substitute medium for cement, like rice husk ash, eggshell residue, baggage ash, etc. Hospital waste management is a huge problem in our society. The annual production of medical waste produced from health care facilities, is around 250,000 tons. The purpose of this study is to determine the feasibility of using hospital waste ash produced from a health care facility as a partial replacement for cement. The quantity of hospital Plastic waste ash (5, 10, 15, and 20% by weight of cement) is the major variable in this study, whereas the amount of cementitious material, water to cementitious material ratio, fine and coarse aggregate content are all constant. Nowadays, there is a need a realistic material like natural sand. Despite the fact that M-sand is used as a substitute for River sand, it comes with a number of drawbacks due to its angular size and inability to fill pore spaces. Silica sand is a silica-containing material that efficiently covers pores in concrete. The primary objective of this research is to partially replace M-Sand with Silica Sand in order to enhance concrete properties. Silica sand is combined with M-Sand in various proportions of 5%, 10%, 15%, and 20%. The tests on fresh and hardened concrete are now complete. The findings show that Silica Sand can be used as a partial substitute for M-Sand.M30 and M45 mix design concrete is used for the experimental investigation. The main important parameters are strength, durability and workability of concrete. The study clearly reveals the investigation into numerous substitutions of cement with hospital plastic waste ash in the mix proportion, 5 % to 20% of its cement weight. The trial mix proportion is carried out for the different properties of workability, durability and strength achieves the optimal level of cement substitution with hospital plastic waste ash. </p&gt

THE ROLE AND PERFORMANCE ON CUSTOMER SATISFACTION OF PRIVATE AND PUBLIC SECTOR BANKS

Customer Satisfaction is a detrimental element of quality of life. However, it is missing in the present competitive world. The changing patterns, working conditions, hyper competition, market dynamics and global reforms have highly influenced the lifestyles of individuals to a great extent. It is also a fact in the case of banks, governments and enterprises. Most of the people have been experiencing public sectors, anxiety, frustration, loneliness. The students, doctors, women, senior citizens, working professionals and others have faced several issues and concerns related to problems as well as physical during the new banks. The lack of communication/ accountability, absence of values and bad habits lead to stormy relationships and abnormal behavioral patterns for self and family. All of these have short, mid and long-term impact on the public and private affecting the quality of life. It indicates that the mental health crisis has emerged as a grave concern not only for India but for the world. The present study intends to recognize the socio-economic, psychological and other factors causing banks and explores its impact on quality of life. The study is significant as it deals with the pandemic, loss of jobs, financial instability, medical emergencies, deaths of close relatives, personality disorders, failure in personal/professional life etc. It is imperative to address these concerns as they would lead to increase in motivation, performance and overall satisfaction towards life. Otherwise, private banks are at risk resulting in increasing crimes, suicides and public issues too