This book systematically summarizes the ideas and technologies used in urine proteome analysis. It argues that change is the core of biomarker definition since the body uses its homeostatic mechanisms to correct changes in the blood. This means that urine is probably a better source of biomarkers than blood. A roadmap to the urinary biomarker era is proposed, and researchers are reminded of the potential opportunities and risks in their study design. Kidney diseases are emphasized as they produce the most significant changes in urine. This book tries to show researchers and graduate students, who are in or entering the field, "all things considered" rather than "the current affair".

Since its inception 14 years ago, CAPRISA has conducted numerous clinical studies that have influenced international TB-HIV treatment guidelines as well as HIV prevention through innovations in the microbicide and vaccine fields. This book provides a historical account of how each of CAPRISA's high impact studies was created, developed, implemented, analysed and communicated. In doing so, the reader is taken on a journey that provides glimpses into the genesis of research ideas and how this ultimately leads to a range of HIV prevention and treatment studies that have impacted the global response to the HIV and TB epidemics. Comprised of 5 sections, the book details the following: HIV epidemic in South Africa and the establishment of a research centre to undertake clinical, epidemiological and laboratory research on HIV. CAPRISA's clinical trials on HIV and HSV-2 prevention. These studies investigated the impact of tenofovir gel as topical antiretroviral pre-exposure prophylaxis (PrEP), implementation of topical PrEP through family planning clinics, conditional cash incentives for HIV prevention, HIV vaccines, and passive immunisation with broadly neutralising antibodies. CAPRISA's research on the treatment of HIV and TB co-infection. A review of the major scientific findings from the CAPRISA studies on acute infection and genital mucosal immunology. Essential support activities for the conduct of clinical trials, including research laboratories and pharmacies, as well as establishing effective communication and sustainable structures for community engagement to maintain effective and respectful partnerships with participating communities. The book concludes with a chapter about the challenges facing future HIV prevention and treatment trials. The CAPRISA Clinical Trials: HIV Treatment and Prevention is a resource for undergraduate and postgraduate students, health care providers, doctors, decision-makers and researchers who are seeking guidance and insights on clinical trials - their creation, conduct and impact.

This combination manual and downloadable resources provide much-needed training on the proper handling of rats used in biomedical research. The downloadable resources include narrated video clips that demonstrate and describe each procedural technique. The manual contains handouts with color illustrations and descriptive text for each technique, including the purpose and application of the procedure, recommended skills, and necessary supplies. It can be used as a training resource and refresher for lab animal veterinarians, veterinary technicians, animal care staff, trainers, and research investigators and staff who work with rats.

Inside this book are reflections on the nature of vision and blindness. Further, there are explorations of interpretive research, and presentations of some seminal and contemporary publications in the field of blindness. The other major fodder for conversation with you the reader is an elaborated example of empirical research entitled Blind Online Learners. Each element of this inquiry is explicitly reflected upon as an example of interpretive research. This book is intended for four intersecting groups of readers. If you are a philosopher, closet or sanctioned, then you cannot ponder the nature of being without due consideration for vision, and cannot contemplate the role of seeing in our lives without listening to the stories of those who are blind. The tales within this text are particularly contemporaneous because they are contextualized by the cyber-phenomena of online learning. This segues to the second group of readers, as the described empirical research was originally intended to bring greater depth and breadth of understanding to the field of educational technology, particularly as it intersects with disability studies. There is a paucity of published literature that has inquired into disabled online learners, and this research study responds to that call. Third, this book may be used as a textbook on approaches to interpretive empirical research. It is as close as one may come to a recipe, walking students through a specific example. Because it is situated in actual empirical research, the intention was that it avoid the trap of being prescriptive or formulaic. Finally, the text is intended for readers interested in the field of blindness. The text reviews some of the seminal and contemporary research on blindness, and then presents an elaborated example of what we can and should expect to emerge in the knowledge production industry, changing what it means to be blind.

Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed: embryonic stem cells, induced pluripotent stem cells, human hair follicle stem cells, bone marrow-derived human mesenchymal stem cells, adipose-derived stem cells, periodontal/progenitor cells, cancer stem cells, and breast cancer stem cells. Because human embryonic stem cells possess the potential to produce unlimited quantities of any human cell type, considerable focus is placed on this type of stem cells in this volume. The role of cancer stem cells, specifically in breast cancer is explained. Transplantation of mesenchymal stem cells to aid the injured brain is included. Immune recovery after stem cells transplantation in severe combined immunodeficiency patients is described. The role of mesenchymal stem cells in enhancing the growth and metastasis of colon cancer is discussed. Clinical application of human follicle stem cells is presented. Treatment of malignant gliomas using genetically-modified neural stem cells as a marker is discussed. The impact of cancer stem cell hypothesis on designing new cancer therapies is explained. In the field of regenerative medicine, the use of stem cells in the repair of the central nervous system, tendon injury, and as a cardiac regenerative medicine is described. The role of DNA methylation in maintaining stemness induced pluripotent stem cells from human extraembryonic amnion cells is discussed. Insights on the understanding of molecular pathways involved in tumor biology are explained, which lead to the development of effective drugs. Information on pathways, such as hedgehog, facilitates targeted therapies in cancer.

Cell based impedance sensing is becoming a new biophysical and cellular technology in cell based analyses. The technology has been used in investigation of cellular growth and death, cell adhesion and migration, cell invasion and cell-cell interactions, cell toxicity, angiogenesis, cell permeability, signal transduction and cellular behaviour under flow conditions. It is a probe free, highly sensitive, and versatile technology platform. Recent development in the technology has also allowed high throughput, automated analyses. It has been widely explored in chemistry, toxicity, cell biology, cancer biology, and other areas of chemistry, medicinal chemistry, life and medical science. Written by experts in the area of cell impedance sensing, including the Nobel Laureate Dr Ivar Giaever, this books covers the background of electric cell-substrate impedance sensing, their applications in cell based investigations, particularly in the area of cancer biology. This book is the first on this technology platform and will be a highly useful reference for molecular and cell biologists, cancer biologists, chemists and biochemists, clinical researchers who work in the areas of cell biology, molecular biology, toxicology, pharmaceutical industry, life science and medical research.

Incidence and mortality of atherosclerosis and coronary heart disease (CHD) vary considerably among races, populations and ethnic groups. Some individuals with low levels of risk factors succumb early to disease while many others with a high risk profile do not. CHD clusters in families and is manyfold increased in first degree relatives of persons with an early onset of the disease. Such studies provide compelling evidence of the high degree of heritability of CHD and its risk factors. This book consolidates the available evidence for the roles of genetics in atherosclerosis, its correlates and its sequelae. It presents and discusses the methodology currently used to elucidate the role of genetics. Separate parts focus on evidence of familial aggregation and ethnic variability of the disease and on monogenic and polygenic inheritance modes including all the recent findings and innovation. The book also contains chapters on the genetic aspects of vessel wall processes, such as early structural findings in histological studies and the variability of coronary anatomic patterns. Polymorphisms at the DNA level (RFLP) are detailed and reviewed. Directions for future research in the exciting and fast developing realm of genetic epidemiology are outlined and the major preventive and public health implications are discussed. Genetic Factors in Coronary Heart Disease provides a systematic review of findings, integrated to offer a comprehensive summary and stepping stone for future research. It will be of interest to investigators in atherosclerosis, genetics, epidemiology, biostatistics, cardiology and public health.

The book provides easy-to-understand diverse specialized topics in toxicology using self- study questions and answers. The answers are in the form of text along with custom made diagrams and explanations that help the student audience to understand and grasp the matter easily. It is written specifically as a study guide for the toxicology board and other examinations.

This is the very first book to deal with sex and gender differences in drug therapy - an increasingly recognized medical need. It starts with an overview on S/G in clinical syndromes and a documentation of the medical and socioeconomic damage caused by gender specific adverse drug effects. Part I covers S/G differences in pharmacokinetics. Researchers will be satisfied by the detailed discussion of the mechanisms of S/G differences in drug effects that represents cutting edge science and includes interaction of drugs with sex hormones, genomic and epigenetic mechanisms. It also covers S/G in drug development, in animal models and clinical development and S/G in drug prescriptions. Part II targets S/G differences in drug effects in cardiovascular, pulmonary, CNS, neuromuscular, neuropsychiatric and metabolic diseases, in cancer, inflammation, and rheumatic diseases, in bacterial and retroviral infections, thrombosis, embolism. New drugs will be discussed.

Blockchain technology (BT) is quietly transforming the world, from financial infrastructure, to the internet-of-things, to healthcare applications. With increasing penetration of BT into various areas of our daily lives, the need arises for better awareness and greater knowledge about the capabilities, benefits, risks, and alternatives to distributed ledger applications. It is hoped that current book will be one of the pioneering collections focusing on blockchain implementations in the area of healthcare, with specific aim to present content in an easy-to-understand and readily accessible way for typical end-users of blockchain-based applications. There are important areas within the fabric of modern healthcare that stand to benefit from implementations of BT. These areas include electronic medical records, quality control, patient safety, finance, device tracking, biostamping/biocertification, redundant storage of critical data, health and liability insurance, medication utilization tracking (including opioid and antibiotic misuse), financial transactions, academics/education, asset tokenization, public health and pandemics, healthcare provider credentialing, and many other potential applications. The ultimate goal of the proposed book would be to provide an integrative, easy-to-understand, and comprehensive picture of the current state of blockchain use in healthcare while actively engaging the reader in a forward-looking, exploratory approach toward future developments in this space. To accomplish this goal, an expert panel of contributors has been assembled, featuring scholars from top global universities and think-tanks.

"Methods in Pulmonary Research" presents a comprehensive review of methods used to study physiology and the cell biology of the lung. The book covers the entire range of techniques from those that require cell cultures to those using in vivo experimental models. Up-to-date techniques such as intravital microscopy are presented. Yet standard methods such as classical short circuit techniques used to study tracheal transport are fully covered. This book will be extremely useful for all who work in pulmonary research, yet need a practical guide to incorporate other established methods into their research programs. Thus the book will prove to be a valuable resource for cell biologists who wish to use organs in their research programs as well biological scientists who are moving their research programs into more cell related phenomena.

This book covers classic epidemiological designs that use a reference/control group, including case-control, case-cohort, nested case-control and variations of these designs, such as stratified and two-stage designs. It presents a unified view of these sampling designs as representations of an underlying cohort or target population of interest. This enables various extended designs to be introduced and analysed with a similar approach: extreme sampling on the outcome (extreme case-control design) or on the exposure (exposure-enriched, exposure-density, countermatched), designs that re-use prior controls and augmentation sampling designs. Further extensions exploit aggregate data for efficient cluster sampling, accommodate time-varying exposures and combine matched and unmatched controls. Self-controlled designs, including case-crossover, self-controlled case series and exposure-crossover, are also presented. The test-negative design for vaccine studies and the use of negative controls for bias assessment are introduced and discussed. This book is intended for graduate students in biostatistics, epidemiology and related disciplines, or for health researchers and data analysts interested in extending their knowledge of study design and data analysis skills. This book Bridges the gap between epidemiology and the more mathematically oriented biostatistics books. Assembles the wealth of epidemiological knowledge about observational study designs that is scattered over several decades of scientific publications. Illustrates the performance of methods in real research applications. Provides guidelines for implementation in standard software packages (Stata, R). Includes numerous exercises, covering simple mathematical proofs, consideration of proposed or published designs, and practical data analysis.

Neuropsychiatric disorders such as schizophrenia, mood disorders, Alzheimer s disease, epilepsy, alcoholism, substance abuse and others are one of the most debilitating illnesses worldwide characterizing by the complexity of the causes, and lacking the laboratory tests that may promote diagnostic and prognostic procedures. Recent advances in neuroscience, genomic, genetic, proteomic and metabolomic knowledge and technologies have opened the way to searching biomarkers and endophenotypes, which may offer powerful and exciting opportunity to understand the etiology and the underlying pathophysiological mechanisms of neuropsychiatric disorders. The challenge now is to translate these advances into meaningful diagnostic and therapeutic advances. This book offers a broad synthesis of the current knowledge about diverse topics of the biomarker and endophenotype strategies in neuropsychiatry. The book is organized into four interconnected volumes: Neuropsychological Endophenotypes and Biomarkers (with overview of methodological issues of the biomarker and endophenotype approaches in neuropsychiatry and some technological advances), Neuroanatomical and Neuroimaging Endophenotypes and Biomarkers, Metabolic and Peripheral Biomarkers and Molecular Genetic and Genomic Markers . The contributors are internationally and nationally recognized researchers and experts from 16 countries. This four-volume handbook is intended for a broad spectrum of readers including neuroscientists, psychiatrists, neurologists, endocrinologists, pharmacologists, clinical psychologists, general practitioners, geriatricians, health care providers in the field of neurology and mental health interested in trends that have crystallized in the last decade, and trends that can be expected to further evolve in the coming years. It is hoped that this book will also be a useful resource for the teaching of psychiatry, neurology, psychology and mental health. "

Cardiorespiratory function is prominently affected by oxidative stress. Cigarette smoking is the archetype of oxidative and nitrative stress and free radical formation. New adverse effects of smoking keep on propping up in research. The chapters provide the comprehensive view of new developments in this area regarding cardiovascular and lung function and muscle catabolism. Alterations in inflammatory cytokines and proteins as well as degradation of muscle proteins due to smoking, by far unrecognized, caused by oxidative stress also are presented. Much less is known about the effect of cognitive stress on vagally-mediated cardiorespiratory function and surprisingly, on vagal immune pathway. The experimental studies also show that clinically important meconium aspiration syndrome contains an oxidative trait which is amenable to antioxidative treatment. This volume creates a source of information on the damaging role of oxidative stress in cardiorespiratory function that has by far not been available.

One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously.
This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents.
Series Editor comments:
"The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

Humans have utilized the bioactive principles of different plants for various beneficial physiological properties including antimicrobial properties for many centuries. However, interests of using medicinal plants declined in the 20th century with the availability of effective synthetic antimicrobial drugs. The development of microbial resistance to various drugs has accelerated research interests towards the use of phytochemicals as alternatives to synthetic drugs in the recent years. This book presents an comprehensive reviews on the antimicrobial and antiviral properties of numerous recently reported phytochemicals, and their mechanisms of antimicrobial actions. Some of the chapters have critically discussed the beneficial and adverse effects of antibacterial, and stimulatory activities of dietary phytochemicals on rumen microbial populations, and gut microbial populations of humans and animals. Microbial adaptation and resistance of microbes to phytochemicals has also been highlighted. On the applied apects, the use of phytochemicals against drug resistance microbes, to treat microbial diseases, for food preservation, to inhibit methanogenic archaea in the rumen, and to modulate lipid biohydrogenating microbial populations to increase conjugated linoleic acids in animal-derived foods have been presented in different chapters.

This book demonstrates the beneficial effects in brain circuits involving memory and attention, reward and social values, decision making and coordination, creativity and persistence of the skills and expertise of continuing education and exposure to the Arts; including chess practice, music/counting, college education and watching movies. These activities were reviewed and investigated using full-spectrum, advanced quantitative imaging techniques. The book highlights extensive applications for this research in common diseases, together with cutting-edge and full-spectrum static and dynamic, functional and structural, regional and inter-network, imaging and phenotypic scales. It will capture the interest of researchers in the areas of neurodevelopmental, neuroplasticity and neuropsychiatric imaging and correlation, as well as disease diagnosis and treatment, and could help convey the methodological innovation and neuroscientific applications of important educational, health and arts/science-related topics.

Despite a half century of structural, biophysical and biochemical investigations of ribonucleic acids, they are still mysterious. RNAs stand at fertile crossroads of disciplines, integrating concepts from genomics, proteomics, dynamics as well as biochemistry and molecular biology. From 20 years it is clear, that genetic regulation of eukaryotic organisms has been misunderstood for the last years that the expression of genetic information is effected only by proteins. Basic understanding of nucleic acids has enhanced our foundation to probe novel biological functions. This is especially evident for RNA molecules whose functionality, maturation, and regulation require formation of correct secondary structure through encoded base-pairing interactions.

Beginning with the Escherichia coli co protein, or bacterial DNA topoisomerase I, an ever-increasing number of enzymes has been identified that catalyze changes in the linkage of DNA strands. DNA topoisomerases are ubiquitous in nature and have been shown to play critical roles in most p- cesses involving DNA, including DNA replication, transcription, and rec- bination. These enzymes further constitute the cellular targets of a number of clinically important antibacterial and anticancer agents. Thus, further studies of DNA topology and DNA topoisomerases are critical to advance our und- standing of the basic biological processes required for cell cycle progression, cell division, genomic stability, and development. In addition, these studies will continue to provide critical insights into the cytofoxic action of drugs that target DNA topoisomerases. Such mechanistic studies have already played an important role in the development and clinical application of antimicrobial and chemotherapeutic agents. The two volumes of DNA Topoisomerase Protocols are designed to help new and established researchers investigate all aspects of DNA topology and the function of these enzymes. The chapters are written by prominent investigators in the field and provide detailed background information and st- by-step experimental protocols. The topics covered in Volume I; DNA Topology and Enzymes, range from detailed methods to analyze various aspects of DNA structure, from linking number, knotting/unknotting, site-specific recombi- tion, and decatenation to the overexpression and purification of bacterial and eukaryotic DNA topoisomerases from a variety of cell systems and tissues.

about the involvement of signaling Transforming growth factor in tumor development and metastasis. plays a central role in the signaling network that controls morphogenesis, 2. THE BASICS OF growth and cell differentiation in SIGNALING multicellular organisms. The different members of this pleiotropic family of 2. 1. receptor signaling growth and differentiation factors seem to The family of growth factors regulate many processes in human disease consists of more than thirty members in and, in particular, tumor development. humans alone (15, 16). They cluster in Our understanding of how two major groups, the group composed of initiated signals are mediated has both the bone morphogenetic proteins increased dramatically in the last fifteen (BMP) and growth and differentiation years. Firstly, the prototype of factors (GDFs), and the group formed by this still constantly growing family, was the Activins, and Nodals. The two identified and cloned (1). Secondly, the groups differ in their use of receptors for family receptors were transmembrane receptors and the identified by expression cloning from subsequent activation of the mammalian tissue culture (2-7). Thirdly, transcriptional mediators (for recent genetic screens in Drosophila reviews see (13, 14, 17)).

Phosphoinositides (PIs) are minor components of cellular membranes that play critical regulatory roles in several intracellular functions. This book describes the main enzymes regulating the turnover of each of the seven PIs in mammalian cells, some of their intracellular functions and some evidence of their involvement in human diseases. Due to the complex inter-relation between the distinct PIs and the plethora of functions that they can regulate inside a cell, this book is not meant to be a comprehensive coverage of all aspects of PIs signalling but rather an overview on the current state of the field and where it could go from here. Phosphoinositide and inositol phosphates interact with and modulate the recruitment and activation of key regulatory proteins and in doing so control diverse functions including cell growth and proliferation, apoptosis, cytoskeletal dynamics, insulin action, vesicle trafficking and nuclear function. Initially, inositide signaling was limited to the PLC pathway; however, it is now clear that all the seven phosphoinositides and more than 30 different inositol phosphates likely have specific signaling functions. Moreover there is a growing list of proteins that are regulated by inositol signaling. This has raised the question as to how inositol signaling can control diverse processes and yet maintain signaling specificity. Controlling the levels of inositol signaling molecules and their subcellular compartmentalisation is likely to be critical. This meeting will bring together scientists from different backgrounds to discuss how understanding inositol signaling may be used to target complex human diseases that manifest themselves when inositol signaling is deregulated.

Machine learning is a novel discipline concerned with the analysis of large and multiple variables data. It involves computationally intensive methods, like factor analysis, cluster analysis, and discriminant analysis. It is currently mainly the domain of computer scientists, and is already commonly used in social sciences, marketing research, operational research and applied sciences. It is virtually unused in clinical research. This is probably due to the traditional belief of clinicians in clinical trials where multiple variables are equally balanced by the randomization process and are not further taken into account. In contrast, modern computer data files often involve hundreds of variables like genes and other laboratory values, and computationally intensive methods are required. This book was written as a hand-hold presentation accessible to clinicians, and as a must-read publication for those new to the methods.

The term epigenetics describes regulatory and information storing mechanisms of specific genes that do not involve any change of their DNA sequence. Epigenetics is closely related to the extensively folded state, in which the genome is packaged, known as chromatin. New genomic tools nowadays allow the genome-wide assessment of, for example, chromatin states and DNA modifications, and led to the discovery of unexpected new epigenetic principles, such as epigenomic memory. This was the start of the field of epigenomics, the relation of which to human health and disease is discussed in this textbook. This book aims to summarize, in a condensed form, the role of epigenomics in defining chromatin states that are representative of active genes (euchromatin) and repressed genes (heterochromatin). Moreover, this book discusses the principles of gene regulation, chromatin stability, genomic imprinting and the reversibility of DNA methylation and histone modifications. This information should enable a better understanding of cell type identities and will provide new directions for studies of, for example, cellular reprograming, the response of chromatin to environmental signals and epigenetic therapies that can improve or restore human health. In order to facilitate the latter, we favor a high figure-to-text ratio following the rule "a picture tells more than thousand words". The content of the book is based on the lecture course "Molecular Medicine and Genetics" that is given by one of us (C. Carlberg) in different forms since 2002 at the University of Eastern Finland in Kuopio. Thematically, this book is located between our textbooks "Mechanisms of Gene Regulation" (ISBN 978-94-017-7741-4) and "Nutrigenomics" (ISBN 978-3-319-30415-1), studying of which may also be interesting to our readers. The book is sub-divided into three sections and 13 chapters. Following the Introduction (section A), section B will explain the molecular basis of epigenomics, while section C will provide examples for the impact of epigenomics in human health and disease. The lecture course is primarily designed for Master level students of biomedicine, but is also frequented by PhD students as well as by students of other bioscience disciplines. Besides its value as a textbook, Human Epigenomics will be a useful reference for individuals working in biomedicine.

Lipids are functionally versatile molecules. They have evolved from relatively simple hydrocarbons that serve as depot storages of metabolites and barriers to the permeation of solutes into complex compounds that perform a variety of signalling functions in higher organisms. This volume is devoted to the polar lipids and their constituents. We have omitted the neutral lipids like fats and oils because their function is generally to act as deposits of metabolizable substrates. The sterols are also outside the scope of the present volume and the reader is referred to volume 28 of this series which is the subject of cholesterol. The polar lipids are comprised of fatty acids attached to either glycerol or sphingosine. The fatty acids themselves constitute an important reservoir of substrates for conversion into families of signalling and modulating molecules including the eicosanoids amongst which are the prostaglandins, thromboxanes and leucotrienes. The way fatty acid metabolism is regulated in the liver and how fatty acids are desaturated are subjects considered in the first part of this volume. This section also deals with the modulation of protein function and inflammation by unsaturated fatty acids and their derivatives. New insights into the role of fatty acid synthesis and eicosenoid function in tumour progression and metastasis are presented.

For most biomedical researchers and academics, preparing conference abstracts and posters is an important part of professional life. With good preparation and practice, all scientists can produce abstracts that act as effective ambassadors for their research. A well designed poster can help you to enhance your professional reputation in addition to communicating your data. This book aims to help you achieve these objectives. This book is designed for you to use when you are actually preparing a conference abstract or poster. It is intended to answer the most frequent questions, and to help you avoid the most common problems and pitfalls. Just dip into any chapter and you will find a range of tips relevant to the abstract or poster you are preparing right now. As a researcher and academic, you need to be able to disseminate and communicate your research work and findings. While many will view writing for peer-reviewed journals as the pinnacle of the academic communication hierarchy, being able to write and present conference abstracts and posters is also extremely important. Taking your work to conferences allows you to meet experts from all around the world, to exchange ideas in person and to network with potential employers and collaborators. 'This book is a gem of useful, practical tips covering the entire process - from reading the abstract submission guidelines, through to writing and laying out your poster and creating e-posters. If you are a novice this is the ideal book to guide you through every step. And, even if you consider yourself an expert, there is bound to be some useful information you can glean from the 500 or so tips. By reading this book, in sequence, or by dipping into relevant chapters, you will have all the necessary help with preparing abstracts and posters right at your fingertips' - Catherine Dunbar in her Foreword.