Unravelling the Mechanisms of Menopause-induced Insulin Resistance: Novel Roles for Estradiol in Skeletal Muscle Mitochondrial Function

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ISBN 13 :
Total Pages : 139 pages
Book Rating : 4.:/5 (968 download)

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Book Synopsis Unravelling the Mechanisms of Menopause-induced Insulin Resistance: Novel Roles for Estradiol in Skeletal Muscle Mitochondrial Function by : Maria Jose Torres

Download or read book Unravelling the Mechanisms of Menopause-induced Insulin Resistance: Novel Roles for Estradiol in Skeletal Muscle Mitochondrial Function written by Maria Jose Torres and published by . This book was released on 2016 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt: Menopause results in a progressive decline in ovarian production of 17[beta]-estradiol (E2), increased adiposity and a higher risk for type-2 diabetes, but hormone replacement therapies containing E2 reverse most of these effects. However, we still lack a comprehensive understanding of the mechanism(s) by which E2 modulates insulin sensitivity (IS) and susceptibility to metabolic disease. By using a short-term ovariectomized mouse (surgical removal of ovaries, OVX) and pharmacological replacement of E2, here we have developed a model to study the short-term effects of menopause and E2 replacement therapies on mitochondrial function and IS, within a simplified context (i.e. in the absence of obesity). Given the primary role that skeletal muscle and liver play in glucose homeostasis, the aims of this work are two-fold. First, to determine whether decreased mitochondrial and cellular redox function represent the underlying molecular mechanisms for menopause-induced insulin resistance, and how E2 replacement can reverse these effects. Second, to determine the effects of ovarian E2 depletion and replacement on liver mitochondrial and redox functions, with a specific emphasis on NADH:ubiquinone oxidoreductase (mitochondrial complex I) kinetics and its associated H2O2 emitting potential. The studies herein provide evidence that E2 protects mitochondrial function and redox homeostasis in skeletal muscle by increasing complex I and IIII activities, enhancing electron transfer supercomplex assembly, preventing free radical leak, and decreasing lipid packing of mitochondrial membranes. We report, for the first time, the detection of E2 in skeletal muscle mitochondria, thus providing compelling evidence that E2 localizes to mitochondrial membranes and regulates mitochondrial function through the "fine-tuning" of electron transfer efficiency. Finally, while OVX by itself did not induce major changes on mitochondrial function in the liver (at least in a short-term OVX model), E2 treatment had detrimental effects on mitochondrial function, particularly targeted to complex I. This highlights the remarkably opposite effects E2 can exert on such critical organelles as the mitochondria across tissues with a different "bioenergetics signature", as well as at physiological versus pharmacological concentrations. Collectively, this study offers insights into novel molecular mechanisms by which menopause sets, and E2 replacement reverses, a pro-diabetogenic state, and further advances our knowledge on the mechanisms behind tissue-specific effects of estrogens. The present findings reveal new horizons in the development of novel pharmacological interventions to prevent metabolic dysfunction in naturally or surgically-induced post-menopausal women.

Mitochondria in Skeletal Muscle Health, Aging and Diseases

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ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (136 download)

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Book Synopsis Mitochondria in Skeletal Muscle Health, Aging and Diseases by :

Download or read book Mitochondria in Skeletal Muscle Health, Aging and Diseases written by and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Skeletal muscle is the most abudant tissue of the human body, making up to 40 to 50% of the human body mass. While the importance of optimal muscle function is well recognized in the athletic field, its significance for general health is often underappreciated. In fact, the evidence that muscle mass, strength and metabolism are essential for our overall health is overwhelming. As the largest protein reservoir in the human body, muscles are essential in the acute response to critical illness such as sepsis, advanced cancer, and traumatic injury. Loss of skeletal muscle mass has also been associated with weakness, fatigue, insulin resistance, falls, fractures, frailty, disability, several chronic diseases and death. As a consequence, maintaining skeletal muscle mass, strength and metabolism throughout the lifespan is critical to the maintenance of whole body health. Mitochondria are fascinating organelles regulating many critical cellular processes for skeletal muscle physiology, including for instance energy supply, reactive oxygen species production, calcium homeostasis and the regulation of apoptosis. It is therefore not surprising that mitochondrial dysfunction has been implicated in a large number of adverse events/conditions and pathologies affecting skeletal muscle health. While the importance of normal mitochondrial function is well recognized for muscle physiology, there are important aspects of mitochondrial biology that are still poorly understood. These include mitochondrial dynamics (fusion and fission processes), morphology and processes involved in mitochondrial quality control (mitophagy). Defining the mechanisms regulating these different aspects of mitochondrial biology, their importance for muscle physiology, as well as the interrelations will be critical for expanding understanding of the role played by mitochondria in skeletal muscle physiology and health. The present research topic provides readers with novel experimental approaches, knowledge, hypotheses and findings related to all aspects of mitochondrial biology in healthy and diseased muscle cells.Skeletal muscle is the most abudant tissue of the human body, making up to 40 to 50% of the human body mass. While the importance of optimal muscle function is well recognized in the athletic field, its significance for general health is often underappreciated. In fact, the evidence that muscle mass, strength and metabolism are essential for our overall health is overwhelming. As the largest protein reservoir in the human body, muscles are essential in the acute response to critical illness such as sepsis, advanced cancer, and traumatic injury. Loss of skeletal muscle mass has also been associated with weakness, fatigue, insulin resistance, falls, fractures, frailty, disability, several chronic diseases and death. As a consequence, maintaining skeletal muscle mass, strength and metabolism throughout the lifespan is critical to the maintenance of whole body health. Mitochondria are fascinating organelles regulating many critical cellular processes for skeletal muscle physiology, including for instance energy supply, reactive oxygen species production, calcium homeostasis and the regulation of apoptosis. It is therefore not surprising that mitochondrial dysfunction has been implicated in a large number of adverse events/conditions and pathologies affecting skeletal muscle health. While the importance of normal mitochondrial function is well recognized for muscle physiology, there are important aspects of mitochondrial biology that are still poorly understood. These include mitochondrial dynamics (fusion and fission processes), morphology and processes involved in mitochondrial quality control (mitophagy). Defining the mechanisms regulating these different aspects of mitochondrial biology, their importance for muscle physiology, as well as the interrelations will be critical for expanding understanding of the role played by mitochondria in skeletal muscle physiology and health. The present research topic provides readers with novel experimental approaches, knowledge, hypotheses and findings related to all aspects of mitochondrial biology in healthy and diseased muscle cells.

Hyperandrogenism in Women

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Publisher : Karger Medical and Scientific Publishers
ISBN 13 : 3318064718
Total Pages : 201 pages
Book Rating : 4.3/5 (18 download)

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Book Synopsis Hyperandrogenism in Women by : R. Pasquali

Download or read book Hyperandrogenism in Women written by R. Pasquali and published by Karger Medical and Scientific Publishers. This book was released on 2019-09-09 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hyperandrogenism profoundly affects women’s lives from lowering self-esteem to changing cognition and affective motivation. The polycystic ovary syndrome (PCOS) is the most common androgen excess disorder worldwide. While it is not the focus of this book, some aspects are discussed. The aim of this book is to improve understanding of androgen excess and its impact on several conditions. Topics include development of adipose tissue in females, insulin sensitivity, congenital adrenal hyperplasia, and Cushing’s disease/syndrome. There is also a discussion of PCOS with emphasis on in utero origins and specific genetic and epigenetic factors. This book provides a wealth of relevant information for every endocrinologist and gynecologist who wants to broaden their knowledge of androgens in various conditions.

Hormones, Metabolism and the Benefits of Exercise

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Publisher : Springer
ISBN 13 : 3319727907
Total Pages : 108 pages
Book Rating : 4.3/5 (197 download)

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Book Synopsis Hormones, Metabolism and the Benefits of Exercise by : Bruce Spiegelman

Download or read book Hormones, Metabolism and the Benefits of Exercise written by Bruce Spiegelman and published by Springer. This book was released on 2018-03-07 with total page 108 pages. Available in PDF, EPUB and Kindle. Book excerpt: The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel “myokines” that might act as new therapeutic agents in the future.

Osteosarcopenia: Bone, Muscle and Fat Interactions

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Publisher : Springer Nature
ISBN 13 : 3030258904
Total Pages : 383 pages
Book Rating : 4.0/5 (32 download)

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Book Synopsis Osteosarcopenia: Bone, Muscle and Fat Interactions by : Gustavo Duque

Download or read book Osteosarcopenia: Bone, Muscle and Fat Interactions written by Gustavo Duque and published by Springer Nature. This book was released on 2019-11-06 with total page 383 pages. Available in PDF, EPUB and Kindle. Book excerpt: This edited work presents the most current evidence on osteosarcopenia from bench to bedside, which is expected to facilitate the understanding of this syndrome and to develop preventive and therapeutic strategies. With our aging population, chronic diseases such as osteoporosis and sarcopenia are becoming highly prevalent. Fortunately, our understanding of the bone and muscle interactions has increased in recent years. This has allowed to the coining of the term osteosarcopenia to describe a syndrome in which these two diseases overlap. This overlap between osteoporosis and sarcopenia has major negative effects not only on our older adults but also on health systems worldwide. Readers will find a highly translational approach that starts with a summary of recent discoveries on stem cells biology, muscle and bone interactions – including the role of local bone and muscle fat – followed by comprehensive reviews on myokines (i.e. myostatin), osteokines (i.e. osteocalcin) and adipokines (i.e. interleukins) as major players and determinants of bone and muscle loss with aging. In addition, the role of sex steroids (i.e. estrogens, androgens), and calciotropic hormones (i.e. parathyroid hormone, vitamin D) in the pathogenesis of this syndrome is also reviewed. Moreover, using practical diagnostic and therapeutic tips, this book summarizes the clinical characteristics of osteosarcopenic patients thus facilitating the diagnosis and treatment of this syndrome in clinical practice. Finally, the book presents the case for the Falls and Fractures Clinic as the optimal model of care for this syndrome, aimed to avoid fragmentation and optimize osteosarcopenia care, and simultaneously prevent falls and fractures in older persons. This book offers relevant information on the mechanisms of osteosarcopenia, and a practical guide on how to identify and treat this geriatric syndrome and its adverse outcomes, which are dramatically affecting our aging population. The work is written by leaders in the field and is especially suited not only to any researcher in the musculoskeletal arena but also to medical specialists and allied health professionals involved in the care of older persons.

Sex Hormone Replacement Therapy

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Publisher :
ISBN 13 : 9781475765083
Total Pages : 152 pages
Book Rating : 4.7/5 (65 download)

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Book Synopsis Sex Hormone Replacement Therapy by : Henry Burger

Download or read book Sex Hormone Replacement Therapy written by Henry Burger and published by . This book was released on 2014-01-15 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Hormonal Pathology of the Uterus

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Publisher : Springer Nature
ISBN 13 : 3030384748
Total Pages : 190 pages
Book Rating : 4.0/5 (33 download)

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Book Synopsis Hormonal Pathology of the Uterus by : Liane Deligdisch-Schor

Download or read book Hormonal Pathology of the Uterus written by Liane Deligdisch-Schor and published by Springer Nature. This book was released on 2020-05-13 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hormonal influences, both natural and iatrogenic, are implicated in the most frequent health issues of women. Endometrial cancer is now the most common gynecologic cancer in the United States and the industrialized world. This cancer is strongly related to hormonal and metabolic factors. In addition, breast cancer treated with hormone therapy (Tamoxifen) may, in some cases, be associated with uterine pathology. Hormone therapy is used to improve the physiological effects and counteract abnormal and deleterious effects of “natural” hormonal activity. Millions of women receive hormone therapy at some point of their life: using oral contraceptives, reproductive technology, treatment for post-menopausal symptoms, among other uses. This book addresses a range of women’s health issues, from fertility to neoplasms, and their relationship with natural and iatrogenic hormonal effects. Chapters include clinical and pathological descriptions, theoretical and practical medical issues, and original studies and cases. Controversial issues in certain hormone therapies are presented with updated concepts based on clinical studies and novel statistical methods. The book will be useful for specialized and general physicians, oncologists, endocrinologists, researchers, medical students, and others in the field of women’s health.

Handbook on Immunosenescence

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Publisher : Springer Science & Business Media
ISBN 13 : 1402090633
Total Pages : 1693 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Handbook on Immunosenescence by : Tamas Fulop

Download or read book Handbook on Immunosenescence written by Tamas Fulop and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 1693 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.

Polycystic Ovary Syndrome

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Publisher : Springer Science & Business Media
ISBN 13 : 1597451088
Total Pages : 361 pages
Book Rating : 4.5/5 (974 download)

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Book Synopsis Polycystic Ovary Syndrome by : Andrea Dunaif

Download or read book Polycystic Ovary Syndrome written by Andrea Dunaif and published by Springer Science & Business Media. This book was released on 2008-01-12 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume includes the latest diagnostic criteria for PCOS and comprises the most up-to-date information about the genetic features and pathogenesis of PCOS. It critically reviews the methodological approaches and the evidence for various PCOS susceptibility genes. The book also discusses additional familial phenotypes of PCOS and their potential genetic basis. All four editors of this title are extremely prominent in the field of PCOS.

Diagnosis and Management of Polycystic Ovary Syndrome

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Publisher : Springer Science & Business Media
ISBN 13 : 038709718X
Total Pages : 275 pages
Book Rating : 4.3/5 (87 download)

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Book Synopsis Diagnosis and Management of Polycystic Ovary Syndrome by : NADIR R. FARID

Download or read book Diagnosis and Management of Polycystic Ovary Syndrome written by NADIR R. FARID and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diagnosis and Management of Polycystic Ovary Syndrome is a comprehensive clinical reference work for primary care physicians, internists, general endocrinologists, obstetricians, gynecologists and students. PCOS is a common but frequently misdiagnosed disease. Many symptoms can be alleviated by early intervention and effective management. Prominent endocrinologists are gathered to detail current research and treatment in this metabolic disorder, affecting a growing population. The chapters are comprehensive, providing cutting edge knowledge on pathogenesis, manifestations, diagnosis and treatment of PCOS. Each chapter will be concise concluding with cogent practice points. The variety of medical issues presenting in PCOS patients result in late referrals or in- appropriate advice. This title will be a tool in a further understanding of the metabolic and genetic basis of PCOS, while providing management strategies.

Oxidative Stress and Chronic Degenerative Diseases

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Publisher : BoD – Books on Demand
ISBN 13 : 953511123X
Total Pages : 516 pages
Book Rating : 4.5/5 (351 download)

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Book Synopsis Oxidative Stress and Chronic Degenerative Diseases by : Jose Antonio Morales-Gonzalez

Download or read book Oxidative Stress and Chronic Degenerative Diseases written by Jose Antonio Morales-Gonzalez and published by BoD – Books on Demand. This book was released on 2013-05-22 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work responds to the need to find, in a sole document, the affect of oxidative stress at different levels, as well as treatment with antioxidants to revert and diminish the damage. Oxidative Stress and Chronic Degenerative Diseases - a Role for Antioxidants is written for health professionals by researchers at diverse educative institutions (Mexico, Brazil, USA, Spain, Australia, and Slovenia). I would like to underscore that of the 19 chapters, 14 are by Mexican researchers, which demonstrates the commitment of Mexican institutions to academic life and to the prevention and treatment of chronic degenerative diseases.

Leptin and Reproduction

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Publisher : Springer Science & Business Media
ISBN 13 : 1461501571
Total Pages : 352 pages
Book Rating : 4.4/5 (615 download)

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Book Synopsis Leptin and Reproduction by : Michael C. Henson

Download or read book Leptin and Reproduction written by Michael C. Henson and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: The isolation of leptin in 1994 and its characterization as a factor influencing appetite, energy balance, and adiposity, immediately thrust the polypeptide into the rapidly growing body of literature centered on the physiology of obesity. The growing clinical awareness of obesity as a major health risk in developed societies dovetailed perfectly with any of a number of roles that leptin might play in this abenant physiological condition. Almost unnoticed amidst the excitement generated by early leptin publications was the suggestion that the "fat hormone" might also regulate a wide range of systems and events important to reproduction, including pubertal development, gonadal endocrinology, fettility, and pregnancy. Recognizing this potential, a relatively small cadre of researchers began to examine leptin specifically as a reproductive hormone, thus creating a new and fertile field of investigation. Interest in this area has since gained momentum and an increased number of participants have now made significant contributions to our understanding of many leptin-related mechanisms that are relevant to reproductive biology. Leptin and Reproduction is the first major volume to specifically address leptin as a reproductive hormone and closely examines the advances made in the short time since this field of interest developed. Preeminent researchers ti'om many of the subdisciplines working within this area present a welcomed compendium of the wealth of related literature and voice novel interpretations of cun'ent advances.

Sex Hormones in Neurodegenerative Processes and Diseases

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Publisher : BoD – Books on Demand
ISBN 13 : 1789230144
Total Pages : 360 pages
Book Rating : 4.7/5 (892 download)

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Book Synopsis Sex Hormones in Neurodegenerative Processes and Diseases by : Gorazd Drevensek

Download or read book Sex Hormones in Neurodegenerative Processes and Diseases written by Gorazd Drevensek and published by BoD – Books on Demand. This book was released on 2018-05-02 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book provides chapters on sex hormones and their modulation in neurodegenerative processes and pathologies, from basic molecular mechanisms, physiology, gender differences, to neuroprotection and clinical aspects for potential novel pharmacotherapy approaches. The book contains 14 chapters written by authors from various biomedical professions, from basic researchers in biology and physiology to medicine and veterinary medicine, pharmacologists, psychiatrist, etc. Chapters sum up the past and current knowledge on sex hormones, representing original new insights into their role in brain functioning, mental disorders and neurodegenerative diseases. The book is written for a broad range of audience, from biomedical students to highly profiled medical specialists and biomedical researchers, helping them to expand their knowledge on sex hormones in neurodegenerative processes and opening new questions for further investigation.

Mitochondria in Obesity and Type 2 Diabetes

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Publisher : Academic Press
ISBN 13 : 0128117524
Total Pages : 460 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Mitochondria in Obesity and Type 2 Diabetes by : Beatrice Morio

Download or read book Mitochondria in Obesity and Type 2 Diabetes written by Beatrice Morio and published by Academic Press. This book was released on 2019-04-12 with total page 460 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria in Obesity and Type 2 Diabetes: Comprehensive Review on Mitochondrial Functioning and Involvement in Metabolic Diseases synthesizes discoveries from laboratories around the world, enhancing our understanding of the involvement of mitochondria in the etiology of diseases, such as obesity and type 2 diabetes. Chapters illustrate and provide an overview of key concepts on topics such as the role of mitochondria in adipose tissue, cancer, cardiovascular comorbidities, skeletal muscle, the liver, kidney, and more. This book is a must-have reference for students and educational teams in biology, physiology and medicine, and researchers.

Advances in Geroscience

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Publisher : Springer
ISBN 13 : 3319232460
Total Pages : 637 pages
Book Rating : 4.3/5 (192 download)

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Book Synopsis Advances in Geroscience by : Felipe Sierra

Download or read book Advances in Geroscience written by Felipe Sierra and published by Springer. This book was released on 2015-11-10 with total page 637 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the first comprehensive overview of a new scientific discipline termed Geroscience. Geroscience examines the molecular and cellular mechanisms that might explain why aging is the main risk factor for most chronic diseases affecting the elderly population. Over the past few decades, researchers have made impressive progress in understanding the genetics, biology and physiology of aging. This book presents vital research that can help readers to better understand how aging is a critical malleable risk factor in most chronic diseases, which, in turn, could lead to interventions that can help increase a healthy lifespan, or ‘healthspan.’ The book begins with an analysis of the Geroscience hypothesis, as well as the epidemiological underpinnings that define aging as a candidate main risk factor for most chronic diseases. Next, each chapter focuses on one particular disease, or group of diseases, with an emphasis on how basic molecular and cellular biology might explain why aging is a major risk factor for it. Coverage in the book includes: cancer, cardiovascular disease, dementias, stroke, Parkinson's and Alzheimer’s diseases, osteoporosis, arthritis, diabetes asthma, emphysema, kidney disease, vision impairment, and AIDS/HIV. It finishes with a chapter on pain in the elderly and an overview of future steps needed to bring the newly acquired knowledge into the clinic and the public at large.

Textbook of Clinical Embryology

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Publisher : Cambridge University Press
ISBN 13 : 110727625X
Total Pages : 408 pages
Book Rating : 4.1/5 (72 download)

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Book Synopsis Textbook of Clinical Embryology by : Kevin Coward

Download or read book Textbook of Clinical Embryology written by Kevin Coward and published by Cambridge University Press. This book was released on 2013-10-31 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: The success of Assisted Reproductive Technology is critically dependent upon the use of well optimized protocols, based upon sound scientific reasoning, empirical observations and evidence of clinical efficacy. Recently, the treatment of infertility has experienced a revolution, with the routine adoption of increasingly specialized molecular biological techniques and advanced methods for the manipulation of gametes and embryos. This textbook – inspired by the postgraduate degree program at the University of Oxford – guides students through the multidisciplinary syllabus essential to ART laboratory practice, from basic culture techniques and micromanipulation to laboratory management and quality assurance, and from endocrinology to molecular biology and research methods. Written for all levels of IVF practitioners, reproductive biologists and technologists involved in human reproductive science, it can be used as a reference manual for all IVF labs and as a textbook by undergraduates, advanced students, scientists and professionals involved in gamete, embryo or stem cell biology.

Recapturing a Future for Space Exploration

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Publisher : National Academies Press
ISBN 13 : 0309163846
Total Pages : 464 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Recapturing a Future for Space Exploration by : National Research Council

Download or read book Recapturing a Future for Space Exploration written by National Research Council and published by National Academies Press. This book was released on 2012-01-30 with total page 464 pages. Available in PDF, EPUB and Kindle. Book excerpt: More than four decades have passed since a human first set foot on the Moon. Great strides have been made in our understanding of what is required to support an enduring human presence in space, as evidenced by progressively more advanced orbiting human outposts, culminating in the current International Space Station (ISS). However, of the more than 500 humans who have so far ventured into space, most have gone only as far as near-Earth orbit, and none have traveled beyond the orbit of the Moon. Achieving humans' further progress into the solar system had proved far more difficult than imagined in the heady days of the Apollo missions, but the potential rewards remain substantial. During its more than 50-year history, NASA's success in human space exploration has depended on the agency's ability to effectively address a wide range of biomedical, engineering, physical science, and related obstacles-an achievement made possible by NASA's strong and productive commitments to life and physical sciences research for human space exploration, and by its use of human space exploration infrastructures for scientific discovery. The Committee for the Decadal Survey of Biological and Physical Sciences acknowledges the many achievements of NASA, which are all the more remarkable given budgetary challenges and changing directions within the agency. In the past decade, however, a consequence of those challenges has been a life and physical sciences research program that was dramatically reduced in both scale and scope, with the result that the agency is poorly positioned to take full advantage of the scientific opportunities offered by the now fully equipped and staffed ISS laboratory, or to effectively pursue the scientific research needed to support the development of advanced human exploration capabilities. Although its review has left it deeply concerned about the current state of NASA's life and physical sciences research, the Committee for the Decadal Survey on Biological and Physical Sciences in Space is nevertheless convinced that a focused science and engineering program can achieve successes that will bring the space community, the U.S. public, and policymakers to an understanding that we are ready for the next significant phase of human space exploration. The goal of this report is to lay out steps and develop a forward-looking portfolio of research that will provide the basis for recapturing the excitement and value of human spaceflight-thereby enabling the U.S. space program to deliver on new exploration initiatives that serve the nation, excite the public, and place the United States again at the forefront of space exploration for the global good.