This book provides a comprehensive overview of the genetic basis underlying endocrine diseases. It covers both the molecular and clinical consequences of these genetic defects, as well as the relevance for clinical care, highlighting issues of genetic counseling. Several endocrine diseases have a genetic background, and contemporary research in the field plays a crucial role in the clinical care of endocrine diseases. In recent years, there have been major developments in our understanding of the genetic basis of endocrine diseases. Several novel genes and mutations predisposing individuals to monogenic endocrine diseases have been discovered, and with the advent of next generation sequencing, a huge amount of new data has become available. Further, novel molecular mechanisms, such as genomic imprinting, have been implicated in the pathogenesis of endocrine diseases. A better understanding of the genetic background of these diseases is relevant not only from the research perspective, but also in terms of clinical care. As such, this book is an essential read for both researchers and clinicians working in the field.

The germfree animal is reared in the laboratory to be bacteria free; its counterpart, the gnotobiotic animal, is exposed to select microorganisms. The need for such an animal model for use in biomedical studies was first expressed by Pasteur in the late 1800s. Subsequent development of germfree and gnotobiotic animals led to an explosion of studies on the effects of microflora and its components on the physiology and metabolism of the host. Germfree and Gnotobiotic Animal Models brings together the most notable points of early and recent studies and gives reference to the most pertinent literature.

This is the first book devoted exclusively to the subject of immunogold-silver staining. This volume is authored by 47 distinguished scientist representing 12 countries. The primary objective of this book is to discuss principles, methods, and applications of IGSS.

Examining the strengths and limitations of various standards of accuracy in clinical laboratory analyses, this detailed reference presents an in-depth study of important theoretical and empirical issues concerning the description, collection, and application of reference values in laboratory medicine.

Based on the presentations given by well-known specialists at a recent multidisciplinary conference of developmental psychobiologists, obstetricians, and physiologists, this book is the first exhaustive attempt to synthesize the present scientific knowledge on fetal behavior. Utilizing a psychobiological analytic approach, it provides the reader with an overview of the perspectives, hypotheses, and experimental results from a group of basic scientists and clinicians who conduct research to elucidate the role of fetal behavior in development. Experimental and clinical as well as human and animal data are explored via comparative developmental analysis. The ontogeny of fetal spontaneous activity -- via the maturation of "behavioral states" -- and of fetal responsiveness to sensory stimulation is studied in detail. Results are provided from studies of embryonic/fetal and newborn behavior in chicks, rats, sheep, primates, and humans. Knowledge of fetal behavior is crucial to the obstetrician, neonatologist, developmental psychologist, and even the future parents, in order to follow and assess the gradual development of spontaneous responsive movements of the fetus. While assessing this important information, this text also examines the neuro-behavioral events taking place during the fetal period as an aid to understanding normal and pathological life span development.

This is a review of what needs to be done to realize the potential of monoclonal antibodies. It assesses the competing technologies with advice on the best approach for a particular situation. Monoclonal antibodies have revolutionized immunology and are now promising to have a similar impact on clinical medicine. Recent developments should overcome many of the difficulties experienced in the past which has seen a great deal of talk about the therapeutic applications of monoclonal antibodies, but very little routine therapy.

Phage Display in Biotechnology and Drug Discovery, Second Edition provides a comprehensive view of the impact and promise of phage display in drug discovery and biotechnology. Building on the success of its previous edition, the book discusses current theories, principles, and methods in the field and demonstrates applications for peptide phage display, protein phage display, and the development of novel antibodies. The book provides readers with an overview of the amazing breadth of the impact that phage display technology has had on the study of proteins in general as well as the development of proteins. It will be a valuable resource for those interested in using phage display and recombinant antibodies in basic research and drug discovery. Key Features: Describes the basic principles of phage display and the methods and systems that have been developed for key applications Outlines applications for peptide phage display in the development of vaccines and high- throughput screens as well as the exploration of protein-protein interactions and enzyme substrate characteristics Details the use of phage display in the engineering of protein stability, the identification and mapping of protein-protein interactions, and the development of catalysts Provides broad coverage of the impact of phage display technology on the development of protein therapeutics Presents expert opinions on future challenges in the field

In 1993, the genetic mutation responsible for Huntington's disease (HD) was identified. Considered a milestone in human genomics, this discovery has led to nearly two decades of remarkable progress that has greatly increased our knowledge of HD, and documented an unexpectedly large and diverse range of biochemical and genetic perturbations that seem to result directly from the expression of the mutant huntingtin gene. Neurobiology of Huntington's Disease: Applications to Drug Discovery presents a thorough review of the issues surrounding drug discovery and development for the treatment of this paradigmatic neurodegenerative disease. Drawing on the expertise of key researchers in the field, the book discusses the basic neurobiology of Huntington's disease and how its monogenic nature confers enormous practical advantages for translational research, including the creation of robust experimental tools, models, and assays to facilitate discovery and validation of molecular targets and drug candidates for HD. Written to support future basic research as well as drug development efforts, this volume: Covers the latest research approaches in genetics, genomics, and proteomics, including high-throughput and high-content screening Highlights advances in the discovery and development of new drug therapies for neurodegenerative disorders Examines the practical realities of preclinical testing, clinical testing strategies, and, ultimately, clinical usage While the development of effective drug treatments for Huntington's disease continues to be tremendously challenging, a highly interactive and cooperative community of researchers and clinical investigators now brings us to the threshold of potential breakthroughs in the quest for therapeutic agents. The impressive array of drug discovery resources outlined in the text holds much promise for treating this devastating disease, providing hope to long-suffering Huntington's disease patients and their families.

Bioengineering is the application of engineering principles to address challenges in the fields of biology and medicine encompassing the principles of engineering design to the full spectrum of living systems. In surgery, recent advances in minimal invasive surgery and robotics are the culmination of the work that both engineers and surgeons have achieved in the medical field through an exciting and challenging interface. This interface rests on the medical curiosity and engineering solutions that lead eventually to collaboration and development of new ideas and technologies. Most recently, innovation by surgeons has become a fundamental contribution to medical research in the surgical field, and it is through effective communication between surgeons and biomedical engineers and promoting collaborative initiatives that translational research is possible. Bioengineering for Surgery explores this interface between surgeons and engineers and how it leads to innovation processes, providing clinical results, fundraising and prestige for the academic institution. This book is designed to teach students how engineers can fit in with their intended environment and what type of materials and design considerations must be taken into account in regards to medical ideas.

Overall, this book illustrates the complexities of the regulation and deregulation of genes mediated through epigenetics in the development and progression of human malignancies. All the articles have been carefully chosen to represent several cancer systems with state of our knowledge on the role of epigenetic deregulation of microRNAs (miRNAs) and their target mRNAs along with epigenetic deregulation of mRNAs. This book also illustrates the role of several dietary agents, collectively called nutraceuticals or natural agents in modulating the epigenetic reprogramming of miRNAs and mRNAs for the prevention and/or treatment of human malignancies. It is well known that genetic aberrations, especially inherited through parents (somatic genetic alterations) contribute to the development of less than 10% of all cancer yet epigenetic alterations in genes especially through selective methylation and acetylation appears to be responsible for the development and progression of the vast majority of all cancers. Therefore, understanding the role of epigenetics in the regulation of genes especially through deregulated expression of miRNAs as presented in this book will allow scientists to devise targeted therapeutic strategies for re-expression of the lost genes or down-regulate the genes that are over-expressed in order to eradicate cancer. It is hoped that targeting epigenetics will not only target cancer cells but it will also target the tumor microenvironment (more like the entire tumor environment such as the entire host) for achieving better treatment outcomes for patients diagnosed with cancer which will lead to achieve the long-term objective for complete eradication of cancer. This book contains fifteen chapters which begins with the concept of systems and network biology for investigating the epigenetics of cancer followed by a series of articles on the role of miRNAs and their target genes in the biology of pancreatic cancer and other cancers such as breast, kidney, prostate and and colon. Since it is becoming increasingly clear that cancer stem cells (CSCs) are important in the development and progression of cancer, and CSCs are important in therapeutic resistance, treatment failure and tumor recurrence, thus the importance of CSCs and epigenetics has been highlighted by a very timely article on epigenetic variations of stem cell markers in cancer including miRNAs. Moreover, just targeting heterogeneous cancer cell populations may not be optimal to eradicate tumors and for which one must take a holistic approach for developing drugs that could also target the tumor microenvironment and tumor dormancy that are regulated through epigenetics. Keeping abreast with this thought process the concluding chapter provides a concept towards curative cancer therapy with maspin, which could be a unique window of opportunity to target tumor dormancy. Therefore, it suggest that targeting the tumor dormancy and the tumor microenvironment using novel therapeutics specifically by targeting epigenetics would become the future of medicine.

Evidence from randomized controlled clinical trials is widely accepted as the only sound basis for assessing the efficacy of new medical treatments. Statistical methods play a key role in all stages of these trials, including their justification, design, and analysis. This second edition of Introduction to Randomized Controlled Clinical Trials provides a concise presentation of the principles applied in this area. It details the concepts behind randomization and methods for designing and analyzing trials and also includes information on meta-analysis and specialized designs, such as cross-over trials, cluster-randomized designs, and equivalence studies. This latest edition features new and revised references, examples, exercises, and a new chapter dedicated to binary outcomes and survival analysis. It also presents numerous examples taken from the medical literature, contains exercises at the end of each chapter, and offers solutions in an appendix. The author uses Minitab and R software throughout the text for implementing the methods that are presented. Comprehensive and accessible, Introduction to Randomized Controlled Clinical Trials is well-suited for those familiar with elementary statistical ideas and methods who want to further their knowledge of the subject.

This monograph contains six chapters, each of which provides details about recent advancements in the field of medicine and biology. Chapter One describes the discovery of AZQ, a drug specifically designed to shut off genes that cause brain cancer. Chapter Two analyses the structure, stability, adaptation to extreme environments and the catalytic mechanism of I+/--helical membrane proteins. Chapter Three provides an up-to-date overview of artificial intelligence (AI) in assisted reproductive treatment (ART) clinics and explores how AI learns and develops a dataset to provide clinical guidance. Chapter Four consists of a study focused on the etiopathogenesis of primary open angle glaucoma using laboratory mice. Chapter Five presents and comments on the current evidence regarding diagnostics in patients with metastatic breast cancer based on circulating tumour cells (CTCs). Lastly, Chapter Six reviews the pathogenetic and clinical features of inner ear involvement in congenital cytomegalovirus (cCMV), the most frequent non-genetic cause of permanent sensorineural hearing loss in childhood.

Handbook of Mouse Mutations with Skin and Hair Abnormalities presents 48 mouse mutations that are all available to the biomedical community. Many of the mouse mutations with dermatological diseases are reviewed and illustrated in detail. This popular reference book gives you a single source to use when determining which mouse mutation will best serve your needs as a biomedical tool for sophisticated research projects.

The book also includes an overview of domestic animal genodermatoses to provide alternatives to mouse models that do not exist or to complement those that do. A detailed section written by renowned experts compares the biology of human and mouse skin and skin diseases in the areas of development and the use of animal models, mammalian genetics, keratin biochemistry, epidermal and hair follicle cycles and kinetics, cytokines and growth factors, keratinocyte culture systems, cutaneous carcinogenesis, cutaneous immune system, and skin changes associated with mutations of the endocrine system.

Metalloproteins comprise approximately 30% of all known proteins, and are involved in a variety of biologically important processes, including oxygen transport, biosynthesis, electron transfer, biodegradation, drug metabolism, proteolysis, and hydrolysis of amides and esters, environmental sulfur and nitrogen cycles, and disease mechanisms. EPR spectroscopy has an important role in not only the geometric structural characterization of the redox cofactors in metalloproteins but also their electronic structure, as this is crucial for their reactivity. The advent of x-ray crystallographic snapshots of the active site redox cofactors in metalloenzymes in conjunction with high-resolution EPR spectroscopy has provided detailed structural insights into their catalytic mechanisms.

This volume was conceived in 2005 at the Rocky Mountain Conference on Analytical Chemistry (EPR Symposium) to highlight the importance of high-resolution EPR spectroscopy to the structural (geometric and electronic) characterization of redox active cofactors in metalloproteins. We have been fortunate to have enlisted internationally recognized experts in this joint venture to provide the scientific community with an overview of high-resolution EPR and its application to metals in biology. This volume, High-Resolution EPR: Applications to Metalloenzymes and Metals in Medicine, covers high-resolution EPR methods, iron proteins, nickel and copper enzymes, and metals in medicine. An eloquent synopsis of each chapter is provided by John Pilbrow in the Introduction.A second volume, Metals in Biology: Applications of High-Resolution EPR to Metalloenzymes, will appear later this year covering the complement of other metalloproteins.

One of the pioneers in the development of pulsed EPR and its application to metalloproteins was Arthur Schweiger, whose contribution we include in this volume. Unfortunately, he passed away suddenly during the preparation of this volume. The editors and coauthors are extremely honored to dedicate this volume to the memory of Arthur Schweiger in recognition of his technical advances and insights into pulsed EPR and its application to metalloproteins. Arthur was extremely humble and treated everyone with equal respect. He was a gifted educator with an ability to explain complex phenomena in terms of simple intuitive pictures, had a delightful personality, and continues to be sadly missed by the community.

It is an honor for the editors to facilitate the dissemination of these excellent contributions to the scientific community. Suggestions for future volumes are always appreciated."

Public health researchers and clinicians regularly work with people who have suffered physical and mental trauma. Knowing how to conduct a study or treat a patient while navigating deep emotional issues requires special skills and overall awareness of how trauma can impact the process and outcomes of participating in research and/or receiving health care. This book presents a diverse array of case examples from scholars of health-related topics, focusing on biographical narrative as a window into understanding key needs in trauma informed scholarship and medicine. Exploring stories from people of varied backgrounds, experiences, and contexts can help professionals within and beyond the academic research and clinical care spheres create rewarding experiences for patients. Negotiating the Emotional Challenges of Conducting Deeply Personal Research in Health will be of interest to public health practitioners, educators and researchers as well as students.

This book presents a comprehensive overview of important immune molecules and their structure-function relationships. The immune system is highly complex, consisting of a network of molecules, cells, tissues and organs, and the immune reaction is involved in various physiological as well as pathological processes, including development, self-tolerance, infection, immunity, and cancer. Numerous molecules participate in immune recognition, inhibition and activation, and these important immune molecules can be roughly divided into cell surface receptors, intracellular receptors and intracellular signaling molecules. The study of how these immune molecules function at molecular level has laid the foundation for understanding the immune system. The book provides researchers and students with the latest research advances concerning the structural biology of key immune molecules/pathways, and offers immunologists essential insights into how these immune molecules function.

If we will ever achieve Paul Ehrlich's "magic bullet," that is, a molecule which goes with high selectivity to the therapeutic target site, does what it needs to do, and is subsequently cleared from the body, the practice of safety assessment will have to change. Nonclinical Drug Administration: Formulations, Routes and Regimens for Solving Drug Delivery Problems in Animal Model Systems seeks to address a trio of objectives that, though separate, are linked and central to biomedical science and, ultimately, medicine. Rather seeing these as separate "silos," those working in nonclinical safety assessment will have to view these three in an integrated manner and to regularly and thoughtfully incorporate new information and technology. The trio of objectives this book explores are: first, to present how to deliver more of a drug product systemically to facilitate the regulatory need for evaluating safety and efficacy in animal species (at elevated exposure levels) prior to advancing the drug to human testing; second is to achieve better tolerance to therapeutics administration in test animals and humans which achieves objectives 1 and 3; and third, to explore ways to improve on therapeutic target receptor delivery performance, therefore improving both clinical pharmacodynamics bioavailability and specificity. The book's ten chapters assemble the basic concepts, principles and hypotheses involved in quantitative receptor and chronological organism interaction dynamics central to the successful development of new therapeutics which depend on systemic administration to achieve desired therapeutic goals and in so doing avoid outcomes which limit, marginalize, or preclude the therapeutic use of so many molecules.

This reference provides a comprehensive overview of recent developments in basic research that are relevant to the application of retinoids for cancer prevention and treatment.;Organized in a quick-referral format by specific disease site, this book: describes the effects of retinoids on squamous differentiation in normal, pre-malignant, and malignant epithelial tissues; addresses the mechanisms by which cultured keratinocytes respond to retinoids; considers the antitumor activity of combination therapy with retinoids and cytokines; reviews the toxicity profiles of the vitamin A molecule and the synthetically derived retinoid compounds and their effects on humans; examines the use of retinoids in the prevention of basal cell carcinoma and squamous cell carcinoma (SCC) and in the therapy of advanced SCC; and summarizes data on the potential of retinoids to prevent epithelial cancer, to act as adjuvants to current therapies in early stages of the disease and to aid in the management of both solid tumours and hematologic malignancies.;A guide for the many disciplines involved in the preclinical studies and direct care of cancer patients, this book serves as useful reading for clinical, surgical and radiation oncologists; clinical immunologists; dermatologists; obstetricians/gynaecologists; haematologists; otolaryngologists; internists; nutritionists; and pulmonary-disease specialists.

This book provides candidates with an easy-to-use exam-oriented text that covers most aspects of critical appraisal. It presents concepts in a user-friendly format, particularly for the benefit of those who find epidemiological and statistical concepts rather migraine-inducing.

Imaging Drug Action in the Brain is an outstanding reference that provides detailed methodological information and presents a current review of information obtained using various methods to delineate the neuroanatomy of drug action. It presents material covering selective lesioning and intracranial injections in intact animals. It examines various applications of receptor binding techniques and their importance in pharmacology. In vivo metabolic mapping studies to delineate the distributions of action of psychoactive drugs in animals are reviewed in detail. Imaging Drug Action in the Brain presents recent advances in extending these types of studies to human investigations, using positron emission tomography (PET) scanning and electrophysiological imaging techniques. Applications of immunocytochemical and molecular biology techniques in studies of drug action are explained. Imaging Drug Action in the Brain is the only book that encompasses all of these techniques with up-to-date examples of their applications. It is an essential resource for researchers in the fields of neuropharmacology, neuroanatomy, neurophysiology, and nuclear medicine.

Stem Cell Research takes a multi-disciplinary approach to the topic of human embryonic stem cell research, starting with the breakthrough discovery up through the present day controversy. The book invites the reader to join the conversation by providing a well balanced approach to many of the issues surrounding the development of this controversial scientific field. It includes the thoughts and experiences of scientists, journalists and ethicists as it tried to approach the topic through a variety of different academic disciplines. The book will help the non-scientist understand the biology, research regulations and funding; and simultaneously it will help the scientist better comprehend the full spectrum of ethical, religious, and policy debates.

Exercise and Disease reviews the role of exercise and physical fitness in the prevention or causation of cancer. Relevant mechanistic studies, particularly immunomodulation, are emphasized. The book also interprets effects of long-term exercise on immune functions and data that shows how exercise influences disease resistance. On the other hand, exercise may be involved in immune mediated motion injuries. Finally, exercise plays a potential role in cancer therapy. The book will be useful to researchers interested in the most recent developments and their interpretations.

Health care delivery is undergoing intense scrutiny and pressure for change: people have high expectations and want value for money. Research can do much to evaluate the effectiveness of health care, but deeply rooted disciplinary preconceptions - about what should be done and how, and about what is scientific - have hampered relevant research. "Researching Health Care" brings together an international team of health researchers from the fields of clinical care, clinical epidemiology, bio-statistics, sociology, health economics and health policy. The problem of research method is central to the evaluation of health care, and the contributors therefore focus on the three most important methods in use at present: experimental methods, surveys and other quantitative methods, and qualitative methods. The strengths and limitations of each method are spelled out, and the contributors show how some methods are more appropriate for evaluating the technical aspects of medicine, others for social and community issues. They argue that complex health care problems can be adequately addressed only by an equally broad range of research study designs, as well as by a willingness to co-operate. Th

Publisher's Note: Products purchased from Third Party sellers are not guaranteed by the publisher for quality, authenticity, or access to any online entitlements included with the product. The world-renowned experts at JAMA (R) explain statistical analysis and the methods used in medical research Written in the language and style appropriate for clinicians and researchers, this new JAMA Guide to Statistics and Methods provides explanations and expert discussion of the statistical analytic approaches and methods used in the medical research reported in articles appearing in JAMA and the JAMA Network journals. This addition to the JAMAevidence (R) series is particularly timely and necessary because today's physicians and other health care professionals must pursue lifelong learning to keep up with the ever-expanding universe of new medical science and evidence-based clinical information. Readers and users of research articles must have a firm grasp of the myriad new statistical, analytic, and methodologic approaches used in contemporary medical studies. To provide concrete examples, the explanations in the book link to research articles that incorporate the specific statistical test or methodological approach being discussed.

Meta-analysis is the application of statistics to combine results from multiple studies and draw appropriate inferences. Its use and importance have exploded over the last 25 years as the need for a robust evidence base has become clear in many scientific areas, including medicine and health, social sciences, education, psychology, ecology, and economics. Recent years have seen an explosion of methods for handling complexities in meta-analysis, including explained and unexplained heterogeneity between studies, publication bias, and sparse data. At the same time, meta-analysis has been extended beyond simple two-group comparisons of continuous and binary outcomes to comparing and ranking the outcomes from multiple groups, to complex observational studies, to assessing heterogeneity of effects, and to survival and multivariate outcomes. Many of these methods are statistically complex and are tailored to specific types of data. Key features Rigorous coverage of the full range of current statistical methodology used in meta-analysis Comprehensive, coherent, and unified overview of the statistical foundations behind meta-analysis Detailed description of the primary methods for both univariate and multivariate data Computer code to reproduce examples in chapters Thorough review of the literature with thousands of references Applications to specific types of biomedical and social science data Supplementary website with code, data, sample chapters, and errata This book is for a broad audience of graduate students, researchers, and practitioners interested in the theory and application of statistical methods for meta-analysis. It is written at the level of graduate courses in statistics, but will be of interest to and readable for quantitative scientists from a range of disciplines. The book can be used as a graduate level textbook, as a general reference for methods, or as an introduction to specialized topics using state-of-the art methods.