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Antibiotics represent one of the most successful forms of therapy in medicine. But the efficiency of antibiotics is compromised by the growing number of antibiotic-resistant pathogens. Antibiotic resistance, which is implicated in elevated morbidity and mortality rates as well as in the increased treatment costs, is considered to be one of the major global public health threats (www.who.int/drugresistance/en/) and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public (http://ec.europa.eu/dgs/health_consumer/docs/road-map-amr_en.pdf: http://www.who.int/drugresistance/amr_global_action_plan/en/; http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf). Understanding the mechanisms by which bacteria successfully defend themselves against the antibiotic assault represent the main theme of this eBook published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy. The articles in the eBook update the reader on various aspects and mechanisms of antibiotic resistance. A better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics while minimizing the emergence of antibiotic resistance among pathogens.
It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.
AN AUTHORITATIVE SURVEY OF CURRENT RESEARCH INTO CLINICALLY USEFUL CONVENTIONAL AND NONCONVENTIONAL ANTIBIOTIC THERAPEUTICS Pharmaceutically-active antibiotics revolutionized the treatment of infectious diseases, leading to decreased mortality and increased life expectancy. However, recent years have seen an alarming rise in the number and frequency of antibiotic-resistant "Superbugs." The Centers for Disease Control and Prevention (CDC) estimates that over two million antibiotic-resistant infections occur in the United States annually, resulting in approximately 23,000 deaths. Despite the danger to public health, a minimal number of new antibiotic drugs are currently in development or in clinical trials by major pharmaceutical companies. To prevent reverting back to the pre-antibiotic era—when diseases caused by parasites or infections were virtually untreatable and frequently resulted in death—new and innovative approaches are needed to combat the increasing resistance of pathogenic bacteria to antibiotics. Bacterial Resistance to Antibiotics – From Molecules to Man examines the current state and future direction of research into developing clinically-useful next-generation novel antibiotics. An internationally-recognized team of experts cover topics including glycopeptide antibiotic resistance, anti-tuberculosis agents, anti-virulence therapies, tetracyclines, the molecular and structural determinants of resistance, and more. Presents a multidisciplinary approach for the optimization of novel antibiotics for maximum potency, minimal toxicity, and appropriated degradability Highlights critical aspects that may relieve the problematic medical situation of antibiotic resistance Includes an overview of the genetic and molecular mechanisms of antibiotic resistance Addresses contemporary issues of global public health and longevity Includes full references, author remarks, and color illustrations, graphs, and charts Bacterial Resistance to Antibiotics – From Molecules to Man is a valuable source of up-to-date information for medical practitioners, researchers, academics, and professionals in public health, pharmaceuticals, microbiology, and related fields.
The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.
This book presents a thorough and authoritative overview of the multifaceted field of antibiotic science – offering guidance to translate research into tools for prevention, diagnosis, and treatment of infectious diseases. Provides readers with knowledge about the broad field of drug resistance Offers guidance to translate research into tools for prevention, diagnosis, and treatment of infectious diseases Links strategies to analyze microbes to the development of new drugs, socioeconomic impacts to therapeutic strategies, and public policies to antibiotic-resistance-prevention strategies
Dr. Joshua Lederberg - scientist, Nobel laureate, visionary thinker, and friend of the Forum on Microbial Threats - died on February 2, 2008. It was in his honor that the Institute of Medicine's Forum on Microbial Threats convened a public workshop on May 20-21, 2008, to examine Dr. Lederberg's scientific and policy contributions to the marketplace of ideas in the life sciences, medicine, and public policy. The resulting workshop summary, Microbial Evolution and Co-Adaptation, demonstrates the extent to which conceptual and technological developments have, within a few short years, advanced our collective understanding of the microbiome, microbial genetics, microbial communities, and microbe-host-environment interactions.
This global tuberculosis report is the first to be produced in the era of the SDGs and the End TB Strategy. It provides an assessment of the TB epidemic and progress in TB diagnosis, treatment, and prevention efforts as well as an overview of TB-specific financing and research. It also discusses the broader agenda of universal health coverage, social protection, and other SDGs that have an impact on health. Data was available for 202 countries and territories that account for over 99% of the world's population and TB cases.
Nowadays the term dose-response is used in many different contexts and many different scientific disciplines including agriculture, biochemistry, chemistry, environmental sciences, genetics, pharmacology, plant sciences, toxicology, and zoology. In the 1940 and 1950s, dose-response analysis was intimately linked to evaluation of toxicity in terms of binary responses, such as immobility and mortality, with a limited number of doses of a toxic compound being compared to a control group (dose 0). Later, dose-response analysis has been extended to other types of data and to more complex experimental designs. Moreover, estimation of model parameters has undergone a dramatic change, from struggling with cumbersome manual operations and transformations with pen and paper to rapid calculations on any laptop. Advances in statistical software have fueled this development. Key Features: Provides a practical and comprehensive overview of dose-response analysis. Includes numerous real data examples to illustrate the methodology. R code is integrated into the text to give guidance on applying the methods. Written with minimal mathematics to be suitable for practitioners. Includes code and datasets on the book’s GitHub: https://github.com/DoseResponse. This book focuses on estimation and interpretation of entirely parametric nonlinear dose-response models using the powerful statistical environment R. Specifically, this book introduces dose-response analysis of continuous, binomial, count, multinomial, and event-time dose-response data. The statistical models used are partly special cases, partly extensions of nonlinear regression models, generalized linear and nonlinear regression models, and nonlinear mixed-effects models (for hierarchical dose-response data). Both simple and complex dose-response experiments will be analyzed.
Globalization of the food supply has created conditions favorable for the emergence, reemergence, and spread of food-borne pathogens-compounding the challenge of anticipating, detecting, and effectively responding to food-borne threats to health. In the United States, food-borne agents affect 1 out of 6 individuals and cause approximately 48 million illnesses, 128,000 hospitalizations, and 3,000 deaths each year. This figure likely represents just the tip of the iceberg, because it fails to account for the broad array of food-borne illnesses or for their wide-ranging repercussions for consumers, government, and the food industry-both domestically and internationally. A One Health approach to food safety may hold the promise of harnessing and integrating the expertise and resources from across the spectrum of multiple health domains including the human and veterinary medical and plant pathology communities with those of the wildlife and aquatic health and ecology communities. The IOM's Forum on Microbial Threats hosted a public workshop on December 13 and 14, 2011 that examined issues critical to the protection of the nation's food supply. The workshop explored existing knowledge and unanswered questions on the nature and extent of food-borne threats to health. Participants discussed the globalization of the U.S. food supply and the burden of illness associated with foodborne threats to health; considered the spectrum of food-borne threats as well as illustrative case studies; reviewed existing research, policies, and practices to prevent and mitigate foodborne threats; and, identified opportunities to reduce future threats to the nation's food supply through the use of a "One Health" approach to food safety. Improving Food Safety Through a One Health Approach: Workshop Summary covers the events of the workshop and explains the recommendations for future related workshops.