With the significant medical role that human cytomegalovirus plays in human disease (from acute disease following primary infection, to chronic disease due to life-long viral persistence), the need to better understand human cytomegalovirus biology and pathogenesis is needed. Human Cytomegaloviruses: Methods and Protocols is designed to be an inclusive document covering all of the techniques and approaches necessary to understand and study the pathobiology of human cytomegalovirus. Topics covered include the history of human cytomegaloviruses, techniques to culture and grow the virus in model cell types, the use of primary cells for the study of human cytomegalovirus pathogenesis, modern molecular techniques for assessing the biological consequences of viral infection, animal models for study of cytomegalovirus replication and numerous other topics of current interest. Written in the successful Methods in Molecular Biology series format, each chapter includes an introduction, list of necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Human Cytomegaloviruses: Methods and Protocols serves as a tool for basic scientists as well as clinical scientists with an interest in the basic fundamental aspects of viral gene expression and specific aspects of viral pathogenesis.

One Health is an emerging concept that aims to bring together human, animal, and environmental health. Achieving harmonized approaches for disease detection and prevention is difficult because traditional boundaries of medical and veterinary practice must be crossed. In the 19th and early 20th centuries this was not the case-then researchers like Louis Pasteur and Robert Koch and physicians like William Osler and Rudolph Virchow crossed the boundaries between animal and human health. More recently Calvin Schwabe revised the concept of One Medicine. This was critical for the advancement of the field of epidemiology, especially as applied to zoonotic diseases. The future of One Health is at a crossroads with a need to more clearly define its boundaries and demonstrate its benefits. Interestingly the greatest acceptance of One Health is seen in the developing world where it is having significant impacts on control of infectious diseases.

The aim of this book is to provide readers with a wide overview of the main healthcare-associated infections caused by bacteria and fungi able to grow as biofilm. The recently acquired knowledge on the pivotal role played by biofilm-growing microorganisms in healthcare-related infections has given a new dynamic to detection, prevention and treatment of these infections in patients admitted to both acute care hospitals and long-term care facilities. Clinicians, hygienists and microbiologists will be updated by leading scientists on the state-of-art of biofilm-based infections and on the most innovative strategies for prevention and treatment of these infections, often caused by emerging multidrug-resistant biofilm-growing microorganisms.

Dating Neurological Injury: A Forensic Guide for Radiologists, Other Expert Medical Witnesses, and Attorneys presents a unique way to approach the dating of neurological injury as imaged by modern computed tomography (CT), magnetic resonance (MR) and ultrasound (US). Chapters are presented in a logical progression beginning with the general appearance of normal brain and progressing to the way abnormalities manifest themselves. The emphasis in these discussions is on the appearance of edema and of hemorrhage, as these two findings are the brain's most common response to injury. This volume presents in a systematic fashion the principles involved in the interpretation of images of the central nervous system specifically in a medical-legal setting where concern exists about the occurrence and timing of an injury. Dating Neurological Injury: A Forensic Guide for Radiologists, Other Expert Medical Witnesses, and Attorneys is a welcome addition to institutional, medical, and legal libraries, and to the personal libraries of malpractice defense and plaintiff lawyers and physicians in the neurosciences (neurosurgery, neurology, neuropathology, and neuroradiology) involved in medical-legal issues.

Featuring the work of several world authorities, this volume places primary emphasis on the mechanism of parasite produced changes in the immune response (i.e. immunosuppression). The text covers parasitic diseases on which the World Health Organization has aggressively promoted research through its Program on Research and Training In Tropical Diseases. Chapters cover parasitic diseases such as malaria, American trypanosomiasis (Chagas' disease), African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and onchocerciasis. Also included are discussions of toxoplasmosis and amebiasis. The material is drawn from the body of literature that has been rapidly accumulating for the last 15 years. An important feature of this text is that the contributors first outline existing knowledge about the immunology of each infection, thereby enabling the reader to more easily appreciate why and how the immunological alterations that accompany a disease are important, and then, to review the postulated mechanisms for such alterations. Consequently, the impact that each parasitic infection has on the immune system is always described in the "heart" of each chapter rather than at the beginning.

Dengue virus (DENV), a mosquito-borne flavivirus, is the causative agent of dengue fever, currently one of the most significant emerging disease challenges to global public health. Although dengue is an old disease, recent decades have seen an unprecedented increase in the geographic range, incidence, and severity of infection. The virus infects 100 million people annually and is endemic in many tropical and sub-tropical regions in the world. At present, neither a licensed vaccine nor anti-viral drugs are available to control dengue disease, prompting a plethora of research initiatives aimed at understanding the molecular and cellular virology, genomics, and evolution of this important virus. This book brings together a panel of expert dengue virologists to produce a timely review of the rapidly-expanding dengue research literature. In addition, the contributors identify the most pressing questions that remain to be answered, thus providing a stimulus for future research. Topics include: evolutionary history * epidemiology * translation and processing of the viral polyprotein * viral replication * the role of the viral untranslated regions * pathogenesis * host response to DENV * development of animal models * DENV-mosquito interactions * dynamics of dengue virus transmission * emergence of DENV from its ancestral, sylvatic cycle * vaccines * novel anti-dengue drugs * and passive immunotherapy. It is essential reading for every dengue virologist and is highly recommended for all flavivirus and arbovirus virologists.

The acknowledgment that viruses are potent biological factors in driving many cancers have seen a dramatic upsurge in recent years in large part to the success of the human papilloma virus vaccine against invasive cervical carcinomas and followed by the awarding of the noble prize in medicine in 2008 to Dr. Harald zurHausen who identified the link between papilloma virus and cervical cancers. Over the last few years there have been some volumes addressing different aspects of viruses and cancers and to some extent focusing on the DNA viruses, more specifically the human DNA viruses. This proposed volume will attempt to review and address the major gaps in current knowledge in DNA viruses as well as RNA viruses bringing a historical perspective of where studies began to a more recent molecular approach and vaccine successes in tumor viruses. We will also cover other known oncogenic viruses associated cancers in other mammals in addition to humans.

This volume covers all aspects of the antibiotic discovery and development process through Phase II/III. The contributors, a group of highly experienced individuals in both academics and industry, include chapters on the need for new antibiotic compounds, strategies for screening for new antibiotics, sources of novel synthetic and natural antibiotics, discovery phases of lead development and optimization, and candidate compound nominations into development. Beyond discovery , the handbook will cover all of the studies to prepare for IND submission: Phase I (safety and dose ranging), progression to Phase II (efficacy), and Phase III (capturing desired initial indications). This book walks the reader through all aspects of the process, which has never been done before in a single reference. With the rise of antibiotic resistance and the increasing view that a crisis may be looming in infectious diseases, there are strong signs of renewed emphasis in antibiotic research. The purpose of the handbook is to offer a detailed overview of all aspects of the problem posed by antibiotic discovery and development.

Immunocytochemistry and in situ hybridization are widely used biomedical sciences. They are essential in medical diagnosis and in cell biology research. Affinity labeling is the central goal of the experimental strategy involving a series of techniques in a logical order; from the effects of specimen fixation, through specimen preparation to expose the antigen, to optimizing immunolabeling, to assessing the result and finally to safety considerations. Numerous examples of these techniques in biomedical sciences are included, as well as experimental assays and practical tips. This survey of methods will serve as an invaluable reference source in any laboratory setting (academic, industrial or clinical) involved in research in almost every branch of biology or medicine, as well as in pharmaceutical, biotechnological and clinical applications.

This volume covers what is known regarding the natural history, basic biology, and clinical aspects, including imaging and treatment, of CNS metastasis. Three chapters cover the biology of the brain and brain metastases: molecular biology, includes what is known about specific genes/proteins involved in the process of metastasis and model systems to study brain metastasis; brain microenvironment, focuses on the resident cells of the microenvironment and their role in CNS metastasis; and the blood- brain barrier, includes a discussion of permeability with respect to brain metastases. A discussion of experimental imaging covers both the biology of brain metastasis from an imaging perspective and the use of imaging techniques to study brain metastases. The three clinical chapters discuss treatment options of surgery, chemotherapy, and radiation. The potential for novel targeted therapies is also addressed. Because of the uniqueness of the disease, leptomeningeal metastasis is discussed separately. The last chapter is devoted to quality of life issues associated with CNS metastasis.

Histoplasmosis is a fungal disease that is widely endemic in much of the world. In the central United States, including the broad reaches of the Ohio and Mississippi River valleys, the majority of adults are infected with the causative fungus. Most infected individuals handle this infection well, but a few do become sick. Over the years there have been a number of outbreaks or epidemics with many persons becoming severely ill and some dying as a result. This is the story of the discovery of histoplasmosis in 1905 and the subsequent development of knowledge concerning its etiology, pathogenesis, epidemiology, diagnostic challenges, clinical manifestations, and treatment. Uniquely qualified to tell this tale, Daniel and Baum base their study on original source material not previously available.

The story of histoplasmosis spans the twentieth century, from its discovery by Samuel Taylor Darling in Panama to the development of effective drug treatment near the century's end. The book epitomizes the growth of medical knowledge through the confluence of ideas and information arising from the work of many individual investigators, a recurrent theme in the history of medicine. Daniel and Baum include much original and previously unreported material derived from BauM's direct involvement with the unraveling of the pathogenesis of the disease and his personal knowledge of the people and events detailed in this book.

Written by specialists in the different fields, this book presents new perspectives and insights into strategies and weapons to fight microbial infections. It also reviews the "state of the art" of alternative treatment approaches and new therapeutic agents to deal with infections caused by multidrug-resistant microorganisms. In an era of accumulated resistance to current antibiotics, it is vital that this is undertaken without further delay. Aspects discussed include the control of RNA synthesis, the use of bacteriocins or enzybiotics (bacteriophages or purified lysins), the specific control of pathogenic clostridia, the design of new drugs affecting DNA synthesis in bacteria, the use of fecal-matter transplant strategies, the specific control of quorum sensing responses in bacteria, the use of new peptides as antibiotics and new ways to control bacteria that cause cancer, such as Helicobacter pylori cancers.

This comprehensive volume examines the current state of free radical biology and its impact on otology, laryngology, and head and neck function. The chapters collectively highlight the interrelationship of basic and translational studies in each area, define the challenges to translation, and identify the existing basic issues that demand investigation as well as the opportunities for novel intervention to prevent and treat ENT pathology and impairment. In each chapter, or in some cases pairs of chapters, the author(s) have included or married issues of basic research with translational challenges and research, thus defining the pathway by which new basic insights may lead to interventions to prevent or treat impairment. The final chapter of this book reflects a meeting of all the contributors, culminating in a discussion and "white paper" that identifies the challenges to the field and defines the studies and collaborations that may lead to improved understanding of free radical biology in ENT and, subsequently, new interventions to medically treat ENT pathology.

The difference among pluripotent stem cells, multipotent stem cells, and unipotent stem cells is pointed out. Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed: human embryonic stem cells, human mesenchymal stem cells, germ cell-derived pluripotent stem cells, induced pluripotent stem cells, human umbilical cord blood-derived stem cells, breast tumor stem cells,and hematopoietic stem cells. Because of the potential of human embryonic stem cells to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential. Because of their pluripotency, these cells have been used in various applications such as tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. The formation of embryoid bodies, which are three-dimensional aggregates of embryonic stem cells, is explained as this is the first step in cell differentiation. Such embryoid body culture has been widely used as a trigger for the in vitro differentiation of embryonic stem cells. The basic capacity of self-renewal of human embryogenic stem cells is explained. The role of TGF-beta in the propagation of human embryonic stem cells is discussed. The differentiation of human embryonic stem cells into neurons, hepatocytes, cardiomyocytes, and retinal cells is fully explained. Donor policies for hematopoietic stem cells are also explained.

This volume is a collection of chapters from the leading experts in the relatively new and burgeoning field of persister cell studies. Persisters play a leading role in the recalcitrance of chronic infections, and enable the development of classical antibiotic resistance. The focus of the book is on studies that provide an understanding of the mechanisms of persister formation, antibiotic tolerance and role in disease, at the molecular level.

This volume focuses on the role of sphingosine-1-phosphate (S1P) and its analogs in the induced sequestration of lymphocytes in secondary lymphoid organs or in the microenvironment of tissues involved in infection or autoimmune disease. Initial chapters define the pathways to understand S1P signaling. They cover the organization of signaling systems, the structural biology of the S1P1 receptor, and the chemical and genetic tools that are available and useful to explore this area of research and therapeutics. The later chapters highlight S1P and endothelial integrity, lymphocyte migration in the spleen, and S1P agonist in controlling immunopathologic manifestations of acute respiratory influenza virus infection (in the lung), and its accompanying cytokine storm as well as immunopathologic disease of the central nervous system, including the beginning of treatments in multiple sclerosis. One chapter reveals the possible involvement of other lipid molecules, their use for better understanding lipid signaling, and their potential in the modulation of immune responses.

Cardiovascular disease is the leading cause of morbidity and premature death of modern era medicine. It is estimated that approximately 81 million people in the United States (US) currently have one or more of the many forms of cardiovascular disease, resulting in 1 in every 2.8 deaths, or 900,000 deaths per year. 40% of all deaths in Europe are a result of cardiovascular disease in people under the age of 75. Aneurysms form a significant portion of these cardiovascular related deaths and are defined as a permanent and irreversible localised dilation of a blood vessel greater than 50% of its normal diameter. Although aneurysms can form in any blood vessel, the more lethal aneurysms develop in the cranial arteries, and in the thoracic aorta and abdominal aorta. Frequently aneurysms are undetected and if left untreated may eventually expand until rupture with very high levels of morbidity and mortality. The biomechanics and mechanobiology of aneursymal diseases are not fully understood and this monograph aims to provide new insights into aneurysm aetiology and behavior based on the most recent biomechanics research related to this important topic. The contributors to this volume bring together a unique blend of expertise in experimental, computational and tissue biomechanics relating to aneurysm behavior and enable the reader to gain a fresh understanding of key factors influencing aneurysm behavior and treatment. Biological risk factors such as tobacco smoking, sex, age, hypertension, family history and mechanobiological risk factors such as aneurysm geometry and shape as well as mechanical properties of the diseased tissues are considered in detail as are many of the diagnostic and treatment options.

This concise volume describes the latest, up-to-date theory, methodology, and applications of ABC transporters in microorganisms. The topics include the structure, physiology, and evolution of ABC transporters, as well as their special characteristics in specific microorganisms, including bacteria, yeast, trypanosomes, and malaria parasites. In particular, the book describes the most recent research and innovations relative to the role of ABC transporters in the design of strategies to circumvent drug resistance in microorganisms. Each chapter comprises an exhaustive review of the particular topic and provides insights into the future of the field, both from the scientific and clinical perspective. A skillful selection of topics and a panel of acknowledged experts ensure that this concise volume will be of exceptional importance to everyone involved in DNA superfamily research, as well as scientists interested in microbial physiology and multidrug resistance. It is essential reading for anyone involved in this field, and it is a recommended volume for all microbiology laboratories.

This volume covers microbiological, clinical and patophysiological aspects of sepsis and also provides general overview chapters with every chapter discussing the real clinical impact of the discussed diagnostic approaches. Sepsis is a major clinical problem that takes an inordinate toll on human lives and economical resources. It is widely recognized that inappropriate treatment is associated with a dramatic increase in mortality, especially within the first hours, therefore clinical and microbiological diagnosis are of pivotal importance in the management of septic patients. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Sepsis: Diagnostic Methods and Protocols seeks to serve both professionals and novices with its well-honed methodologies in an effort to further our knowledge of this life-threatening illness.

Although antiviral drugs have been successfully developed for some viral diseases, there remains a clear, unmet medical need to develop novel antiviral agents for the control and management of many viruses that currently have no or limited treatment options as well as a need to overcome the limitations associated with the existing antiviral drugs, such as adverse effects and emergence of drug-resistant mutations. The second edition of Antiviral Methods and Protocols features: All chapters are new and written by experts in the field, reflecting the major recent technical advances in antiviral research and discovery. This edition focuses on many important human viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis viruses (hepatitis B and C viruses), herpes viruses, human respiratory syncytial virus (RSV), and influenza virus, while also featuring some important emerging viruses, such as dengue virus, West Nile virus, and chikungunya virus. As a volume in the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Antiviral Methods and Protocols, Second Edition will serve as an excellent laboratory reference for pharmaceutical and academic biologists, medicinal chemists, and pharmacologists as well as for virologists in the field of antiviral research and drug discovery.

Origin and General Nature of Retroviruses; H.M. Temin. Structure and Classification of Retroviruses; J.M. Coffin. Evolutionary Potential of Complex Retroviruses; G.M. Myers, G.N. Pavlakis. Retroelements in Microorganisms; D.J. Garfinkel. Biology of Avian Retroviruses; L.N. Payne. Retroviruses in Rodents; C.A. Kozak, S. Ruscetti. 1 additional article. Index.