Epidemiology of Cytochrome P450-mediated Drug-Drug Interactions

Drug-drug interactions (DDIs) comprise an important cause of adverse drug reactions leading to excess hospitalizations. Drug metabolism is catalyzed by 75% by cytochrome P450 (CYP) enzymes and thus they are often involved in pharmacokinetic DDIs. In general, DDIs are studied in randomized controlled clinical trials in selected study populations. The overall aim of the present studies was to perform observational pharmacoepidemiological surveys on CYP-mediated DDIs in diseases important at the population level. The prevalence of co-administrations of four prodrugs (losartan, codeine, tramadol, and clopidogrel), three sulphonylureas (glibenclamide, glimepiride, and glipizide), or two statins (lovastatin and simvastatin) with well established agents altering CYP activity, as well as of statins with fibrates, was studied in Finland utilizing data from a university hospital medication database (inpatients) and the National Prescription Register of the Social Insurance Institution of Finland, Kela (outpatients). Clinical consequences of potential DDIs were estimated by reviewing laboratory data, and information from hospital care and cause-of-death registers. Concomitant use of study substrates with interacting medication was detected in up to one fifth of patients in both hospital and community settings. Potential CYP3A4 interactions in statin users did not manifest in clear adverse laboratory values but pharmacodynamic DDIs between statins and fibrates predisposed patients to muscular toxicity. Sulphonylurea DDIs with CYP2C9 inhibitors increased the risk of hypoglycaemia. CYP3A4 inhibitor use with clopidogrel was not associated with significant changes in mortality but non-fatal thrombosis and haemorrhage complications were seen less often in this group. Concomitant administration of atorvastatin with clopidogrel moderately attenuated the antithrombotic effect by clopidogrel. The overall mortality was increased in CYP3A4 inducer and clopidogrel co-users. Atorvastatin used concomitantly with prodrug clopidogrel seems to be beneficial in terms of total and LDL cholesterol concentrations, and overall mortality compared with clopidogrel use without interacting medication. In conclusion, CYP-mediated DDIs are a common and often unrecognized consequence of irrational drug prescribing.Siirretty Doriast

Public Health

Public health can be thought of as a series of complex systems. Many things that individual living in high income countries take for granted like the control of infectious disease, clean, potable water, low infant mortality rates require a high functioning systems comprised of numerous actors, locations and interactions to work. Many people only notice public health when that system fails. This book explores several systems in public health including aspects of the food system, health care system and emerging issues including waste minimization in nanosilver. Several chapters address global health concerns including non-communicable disease prevention, poverty and health-longevity medicine. The book also presents several novel methodologies for better modeling and assessment of essential public health issues

Applications and Experiences of Quality Control

The rich palette of topics set out in this book provides a sufficiently broad overview of the developments in the field of quality control. By providing detailed information on various aspects of quality control, this book can serve as a basis for starting interdisciplinary cooperation, which has increasingly become an integral part of scientific and applied research

Critical Thinking Skills Profile of High School Students In Learning Science-Physics

This study aims to describe Critical Thinking Skills high school students in the city of Makassar. To achieve this goal, the researchers conducted an analysis of student test results of 200 people scattered in six schools in the city of Makassar. The results of the quantitative descriptive analysis of the data found that the average value of students doing the interpretation, analysis, and inference in a row by 1.53, 1.15, and 1.52. This value is still very low when compared with the maximum value that may be obtained by students, that is equal to 10.00. This shows that the critical thinking skills of high school students are still very low. One fact Competency Standards science subjects-Physics is demonstrating the ability to think logically, critically, and creatively with the guidance of teachers and demonstrate the ability to solve simple problems in daily life. In fact, according to Michael Scriven stated that the main task of education is to train students and or students to think critically because of the demands of work in the global economy, the survival of a democratic and personal decisions and decisions in an increasingly complex society needs people who can think well and make judgments good. Therefore, the need for teachers in the learning device scenario such as: driving question or problem, authentic Investigation: Science Processes

Decision Support Systems

Decision support systems (DSS) have evolved over the past four decades from theoretical concepts into real world computerized applications. DSS architecture contains three key components: knowledge base, computerized model, and user interface. DSS simulate cognitive decision-making functions of humans based on artificial intelligence methodologies (including expert systems, data mining, machine learning, connectionism, logistical reasoning, etc.) in order to perform decision support functions. The applications of DSS cover many domains, ranging from aviation monitoring, transportation safety, clinical diagnosis, weather forecast, business management to internet search strategy. By combining knowledge bases with inference rules, DSS are able to provide suggestions to end users to improve decisions and outcomes. This book is written as a textbook so that it can be used in formal courses examining decision support systems. It may be used by both undergraduate and graduate students from diverse computer-related fields. It will also be of value to established professionals as a text for self-study or for reference

Shortest Route at Dynamic Location with Node Combination-Dijkstra Algorithm

Abstract— Online transportation has become a basic requirement of the general public in support of all activities to go to work, school or vacation to the sights. Public transportation services compete to provide the best service so that consumers feel comfortable using the services offered, so that all activities are noticed, one of them is the search for the shortest route in picking the buyer or delivering to the destination. Node Combination method can minimize memory usage and this methode is more optimal when compared to A* and Ant Colony in the shortest route search like Dijkstra algorithm, but can’t store the history node that has been passed. Therefore, using node combination algorithm is very good in searching the shortest distance is not the shortest route. This paper is structured to modify the node combination algorithm to solve the problem of finding the shortest route at the dynamic location obtained from the transport fleet by displaying the nodes that have the shortest distance and will be implemented in the geographic information system in the form of map to facilitate the use of the system. Keywords— Shortest Path, Algorithm Dijkstra, Node Combination, Dynamic Location (key words

Tracking the Temporal-Evolution of Supernova Bubbles in Numerical Simulations

The study of low-dimensional, noisy manifolds embedded in a higher dimensional space has been extremely useful in many applications, from the chemical analysis of multi-phase flows to simulations of galactic mergers. Building a probabilistic model of the manifolds has helped in describing their essential properties and how they vary in space. However, when the manifold is evolving through time, a joint spatio-temporal modelling is needed, in order to fully comprehend its nature. We propose a first-order Markovian process that propagates the spatial probabilistic model of a manifold at fixed time, to its adjacent temporal stages. The proposed methodology is demonstrated using a particle simulation of an interacting dwarf galaxy to describe the evolution of a cavity generated by a Supernov

Anti-angiogenic and toxicity effects of Derris trifoliata extract in zebrafish embryo

Introduction: Derris trifoliata has been traditionally used as folk for the treatment of , rheumatic joints, diarrhoea, and dysmenorrhea, and rotenoids isolated from the plant have shown to exhibit anti-cancer properties. This study aimed to assess the toxicity effects and antiangiogenic activity of extract of Derris trifoliata on zebrafish embryo model. Materials and Methods: Zebrafihs embryos were treated with aqueous extract of Derris Trifoliata to evaluate its effects on angiogenesis and zebrafish-toxicity. Angiogenic response was analyzed using whole-mount alkaline phosphatase (AP) vessel staining on 72 hours post fertilization (hpf) zebrafish embryos. Results: 1.0 mg/ml concentration was toxic to zebrafish embryos and embryos exposed to concentrations at 0.5 mg/ml and below showed some malformations. Derris trifoliata aqueous extract also showed some anti-angiogenic activity in vivo in the zebrafish embryo model wereby at high concentration inhibited vessel formation in zebrafish embryo. Conclusions: The anti-angiogenic response of extract of Derris trifoliata in zebrafish in vivo model suggest its therapeutic potential as anti-cancer agent