The auditory perception of sounds (environmental, vocal or music) is one of the 5 principal senses consciously monitored by our brains, and is crucial for many human endeavors as well as quality of life. Loss of optimal performance in this principal sensory system leads to loss of effective communication and intimacy, as well as increased risk of isolation, depression, cognitive decline, and greater vulnerability to predators. The vestibular system ensures that individuals remain upright and effectively monitor their posture within their spatial surroundings, move effectively, and remain focused on visual targets during motion. The loss of vestibular sensitivity results in postural instability, falls, inability to observe the environment during motion, and a debilitating incapacity to function effectively. The sensory cells for both auditory and vestibular systems are located within the inner ear of the temporal bulla. There are many causes of auditory and vestibular deficits, including congenital (or genetic) events, trauma, aging and loud sound exposures. Ototoxicity refers to damage of the auditory or vestibular structures or functions, as the result of exposure to certain pharmaceuticals, chemicals, and/or ionizing radiation exposure that damage the inner ear. Ototoxicity is a major contributor to acquired hearing loss and vestibular deficits, and is entirely preventable. In 2009, the United States Department of Defense initiated the Hearing Center of Excellence (HCE), headquartered in San Antonio, Texas, in response to the prevalence of acquired auditory and vestibular deficits in military and veteran populations. The knowledge shared in this eBook supports the HCE’s mandate to improve aural protection of military and civilian populations worldwide. The last few years have seen significant advances in understanding the cellular mechanisms underlying ototoxic drug-induced hearing loss and vestibular deficits. In this eBook, we present some of these advances and highlight gaps where further research is needed. Selected articles discuss candidate otoprotective agents that can ameliorate the effects of ototoxicity in the context of how they illustrate cellular mechanisms of ototoxicity. Our goal in illustrating these advances in mechanisms of ototoxicity is to accelerate the development of clinical therapies that prevent or reverse this debilitating disorder.

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 brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

Genetics of Deafness offers a journey through areas crucial for understanding the causes and effects of hearing loss. It covers such topics as the latest approaches in diagnostics and deafness research and the current status and future promise of gene therapy for hearing restoration. The book begins by bringing attention to how hearing loss affects the individual and society. Methods of hearing loss detection and management throughout the lifespan are highlighted as is a particularly new development in newborn hearing screening. The challenges of hearing loss, an extremely heterogeneous impairment, are addressed. Additional topics include current research interests, ranging from novel gene identification to their functional validation in the mouse and zebrafish. The book ends with a chapter on the state of the art of gene therapy—an area that is certain to gain increasing attention as molecular mechanisms of deafness are better understood. Genetics of Deafness, written by leading authors in the field, is a must read for clinicians, researchers, and students. It provides much needed insight into the diagnosis and research of hereditary hearing loss.

This compilation focuses on Ototoxicity, the adverse pharmacological reaction affecting the inner ear or auditory nerve, characterised by cochlear or vestibular dysfunction. Although ototoxic medications play an essential role in modern medicine, they can cause harm and lead to significant morbidity. The authors discuss aminoglycoside antibiotics, loop diuretics, platinum-based chemotherapeutic agents, macrolide antibiotics and antimalarial medications which are among the 600 frequently used ototoxic drugs. Next, an overview of cisplatin-associated ototoxicity, namely its clinical features, incidence rates, molecular and cellular mechanisms and risk factors is provided for health care practitioners managing patients with cancer. Ototoxicity and neurotoxicity are defined from the perspective of chemical agents, nicotine and cotinine, that individuals experience through cigarette smoking and environmental tobacco smoke exposure. Mechanisms for toxicity are described by review of animal and human studies revealing changes in peripheral and central auditory structures after exposure to nicotine. The mechanisms of ototoxicity induced by aminoglycoside are also discussed, as well as the usage of these drugs for treatment of several disorders such as Meniere disease, and possible protective agents. In closing, the authors highlight the serious issue of aminoglycoside mediated hearing loss in cystic fibrosis patients, and also discuss alternative approaches for avoiding aminoglycoside-induced cochleotoxicity.

Millions of Americans experience some degree of hearing loss. The Social Security Administration (SSA) operates programs that provide cash disability benefits to people with permanent impairments like hearing loss, if they can show that their impairments meet stringent SSA criteria and their earnings are below an SSA threshold. The National Research Council convened an expert committee at the request of the SSA to study the issues related to disability determination for people with hearing loss. This volume is the product of that study. Hearing Loss: Determining Eligibility for Social Security Benefits reviews current knowledge about hearing loss and its measurement and treatment, and provides an evaluation of the strengths and weaknesses of the current processes and criteria. It recommends changes to strengthen the disability determination process and ensure its reliability and fairness. The book addresses criteria for selection of pure tone and speech tests, guidelines for test administration, testing of hearing in noise, special issues related to testing children, and the difficulty of predicting work capacity from clinical hearing test results. It should be useful to audiologists, otolaryngologists, disability advocates, and others who are concerned with people who have hearing loss.

Biomarkers in Toxicology is a timely and comprehensive reference dedicated to all aspects of biomarkers that relate to chemical exposure and their effects on biological systems. This book includes both vertebrate and non-vertebrate species models for toxicological testing and development of biomarkers. Divided into several key sections, this reference volume contains chapters devoted to topics in molecular-cellular toxicology, as well as a look at the latest cutting-edge technologies used to detect biomarkers of exposure and effects. Each chapter also contains several references to the current literature and important resources for further reading. Given this comprehensive treatment, Biomarkers in Toxicology is an essential reference for all those interested in biomarkers across several scientific and biomedical fields. - Written by international experts who have evaluated the expansive literature to provide you with one resource covering all aspects of toxicology biomarkers - Identifies and discusses the most sensitive, accurate, unique and validated biomarkers used as indicators of exposure and effect of chemicals of different classes - Covers special topics and applications of biomarkers, including chapters on molecular toxicology biomarkers, biomarker analysis for nanotoxicology, development of biomarkers for drug efficacy evaluation and much more