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Cardiovascular Genome Editing

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Genome Editing in Cardiovascular and Metabolic Diseases

Genome Editing in Cardiovascular and Metabolic Diseases Book
Author : Junjie Xiao
Publisher : Springer
Release : 2022-10-30
ISBN : 9789811956416
Language : En, Es, Fr & De

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Book Description :

This book provides the latest research progress on genome editing in cardiovascular and metabolic diseases and includes bioinformatics research methodology of genome editing. Genome editing is a genetic engineering technique precisely modified specific target genes of organism genome, which has been applied to basic theoretical research and production applications from plants and animals to gene therapy of human beings. Cardiovascular and metabolic diseases have become major factors affecting human health worldwide. This book contains information about bioinformatics, genome editing in cardiovascular diseases, genome editing in metabolic diseases and therapeutic effects. It will be useful for biologist, cardiologist, cardiovascular surgeons, endocrinologist, internists, nurses, undergraduate and graduate students in medicine and cell biology and others interested in cardiovascular and metabolic medicine.

Genome Editing

Genome Editing Book
Author : Kiran Musunuru
Publisher : Academic Press
Release : 2021-03-05
ISBN : 0128236477
Language : En, Es, Fr & De

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Book Description :

Genome Editing: A Practical Guide to Research and Clinical Applications is geared towards investigators interested in learning how to use CRISPR-Cas9-based technologies, with a focus on cardiovascular research and clinical applications. Covering a range of topics from the basics of genome editing to design considerations, to assessments and applications, this reference allows readers to get started and establish a full workflow from the beginning of the project to its full completion. With worked examples drawn from real-life experiments, as well as troubleshooting and pitfalls to avoid, the book serves as an essential reference for researchers and investigators in both cardiovascular and biomedical research. Help readers familiarise with the variety of genome-editing approaches that are being applied in cardiovascular research and medicine, i.e., both research applications and clinical applications Understand the use of genome editing through worked examples (based on real-life experiments) in which CRISPR-Cas9 is employed, online tools to design CRISPR-Cas9 reagents, methods to interpret data from genome-editing experiments, the downsides of genome-editing technology - both the scientific and ethical pitfalls to avoid Written in an easy-to-follow manner, guiding readers from the design of the project to its completion Includes unpublished and new methods

Translational Cardiometabolic Genomic Medicine

Translational Cardiometabolic Genomic Medicine Book
Author : Annabelle Rodriguez-Oquendo
Publisher : Academic Press
Release : 2015-09-07
ISBN : 0128004746
Language : En, Es, Fr & De

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Book Description :

Translational Cardiometabolic Genomic Medicine, edited by Dr. Annabelle Rodriguez-Oquendo, is an important resource to postgraduate (medical, dental and graduate) students, postdoctoral fellows, basic scientists, and physician scientists seeking to understand and expand their knowledge base in the field of genomic medicine as it is applied to cardiometabolic diseases. This handbook integrates cutting-edge experimental approaches such as chromatin immunoprecipitation paired end tagging (CHIA-PET), to population studies such as the Multi-Ethnic Study of Atherosclerosis. It encompasses a range of book chapters that highlight bioinformatic approaches to better understanding functionality of the noncoding regions of the human genome to the use of molecular diagnostic testing in predicting increased risk of cardiovascular diseases. Where applicable, this reference also includes chapters related to therapeutic options specifically aligned to molecular targets. Provides comprehensive research on translational genomic medicine Explains state-of-the-art genome editing for stem cells and mouse models with significant relevance to human cardiometabolic disease Includes discussions on the functional effects of single nucleotide polymorphisms and cardiometabolic diseases, stratified by sex and race Encompasses a range of book chapters that highlight bioinformatic approaches to better understanding functionality of the noncoding regions of the human genome

Human Genome Editing

Human Genome Editing Book
Author : National Academies of Sciences, Engineering, and Medicine,National Academy of Medicine,National Academy of Sciences,Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations
Publisher : National Academies Press
Release : 2017-08-13
ISBN : 0309452880
Language : En, Es, Fr & De

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Book Description :

Genome editing is a powerful new tool for making precise alterations to an organism's genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions. Human Genome Editing considers important questions about the human application of genome editing including: balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. This report proposes criteria for heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents 7 general principles for the governance of human genome editing.

Cardiovascular Genomics

Cardiovascular Genomics Book
Author : Mohan K. Raizada,Julian F. R. Paton,Michael J. Katovich,Sergey Kasparov
Publisher : Springer Science & Business Media
Release : 2008-02-24
ISBN : 1592598838
Language : En, Es, Fr & De

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Book Description :

Recognized scientists and clinicians from around the world discuss the most recent molecular approaches to understanding the cardiovascular system in both health and disease. The authors focus on all components of the system, including blood vessels, heart, kidneys, and the brain, and cover disease states ranging from vascular and cardiac dysfunction to stroke and hypertension. The methods described for identifying the genes that cause susceptibility to cardiovascular diseases emphasize the possibility of discovering new drug targets. Authoritative and ground-breaking, Cardiovascular Genomics offers an unprecedented examination of both the cutting-edge scientific approaches now possible and the results obtained from them in the new science of cardiovascular genomics.

Cardiovascular Diseases

Cardiovascular Diseases Book
Author : Nikolaos Papageorgiou
Publisher : Academic Press
Release : 2016-08-05
ISBN : 0128033134
Language : En, Es, Fr & De

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Book Description :

Cardiovascular Diseases: Genetic Susceptibility, Environmental Factors and Their Interaction covers the special heritability characteristics and identifying genetic and environmental contributions to cardiovascular health. This important reference provides an overview of the genetic basis of cardiovascular disease and its risk factors. Included are important topics, ranging from lifestyle choices, risk factors, and exposure, to pollutants and chemicals. Also covered are the influences of Mendelian traits and familial aggregation and the interactions and interrelationships between genetics and environmental factors which, when compared, provide a sound understanding of the interplay between inherited and acquired risk factors. The book provides a much needed reference for this rapidly growing field of study. By combining the latest research within the structured chapters of this reference, a better understanding of genetic and environmental contribution to cardiovascular disease is found, helping to substantiate further investigations in the field and design prevention and treatment strategies. Provides an overview of the genetic basis of cardiovascular disease and its risk factors Reviews several large population-based studies which indicate that exposure to several environmental factors may increase CVD morbidity and mortality, exploring the plausibility of this association by data from animal studies Reflects on future studies to help understanding the role of genes and environmental factors in the development and progression of cardiovascular disease

Cardiovascular Genetics and Genomics for the Cardiologist

Cardiovascular Genetics and Genomics for the Cardiologist Book
Author : Victor J. Dzau, MD,Choong-Chin Liew, PhD
Publisher : John Wiley & Sons
Release : 2008-04-15
ISBN : 0470765941
Language : En, Es, Fr & De

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Book Description :

Until recently, a modest knowledge of genetics was more than adequate for the daily practice of clinical cardiology, but advances in genetics and genomics are changing cardiovascular medicine in fundamental ways. The identification of the genetic basis of several forms of dyslipidemia, hypertension, diabetes, cardiomyopathies, and vascular diseases signalled the new importance of genetics in clinical medicine. In this timely volume, Drs. Dzau and Liew – both pioneers in the area – help cardiologists understand: • how cardiovascular genetics may remodel the way cardiovascular medicine is practiced • what material has immediate relevance to the practicing clinician • how to incorporate genetics and genomics in your practice to ensure up-to-date patient care The book opens with introductory chapters, then discusses: • cardiovascular single gene disorders • cardiovascular polygenic disorders • therapies and applications Outstanding contributors write on their areas of expertise, making Cardiovascular Genetics and Genomics for the Cardiologist both authoritative and comprehensive. If you want to gain a better appreciation of how genetics and genomics are already shaping current practice and may potentially revolutionize cardiology, look no further than this dependable reference.

Genome Editing

Genome Editing Book
Author : Kursad Turksen
Publisher : Springer
Release : 2016-08-09
ISBN : 3319341480
Language : En, Es, Fr & De

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Book Description :

This timely volume explores the use of CRISPR-Cas9 for genome editing, presenting cutting-edge techniques and their applications in treatment of disease. The chapters describe latest methods such as use of targetable nucleases, investigation of the non-coding genome, mouse genome editing, increasing of knock-in efficiency in mouse zygotes, and generation of reporter stem cells; the text contextualizes these methods in treatment of cardiovascular disease, diabetes mellitus, retinitis pigmentosa, and others. The final chapters round out the book with a discussion of controversies and future directions. Genome Editing is an essential, of-the-moment contribution to this rapidly growing field. Drawing from a wealth of international perspectives, it presents novel techniques and applications for the engineering of the human genome. This book is essential reading for all clinicians and researchers in stem cells, regenerative medicine, genomics, biochemical and biomedical engineering- especially those interested in learning more about genome editing and applying it in a targeted, specific way.

Genome Editing and Engineering

Genome Editing and Engineering Book
Author : Krishnarao Appasani
Publisher : Cambridge University Press
Release : 2018-08-23
ISBN : 1107170370
Language : En, Es, Fr & De

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Book Description :

A complete guide to endonuclease-based genomic engineering, from basic science to application in disease biology and clinical treatment.

Human Flourishing in an Age of Gene Editing

Human Flourishing in an Age of Gene Editing Book
Author : Erik Parens,Josephine Johnston
Publisher : Oxford University Press
Release : 2019-07-29
ISBN : 0190940387
Language : En, Es, Fr & De

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Book Description :

International uproar followed the recent announcement of the birth of twin girls whose genomes had been edited with a breakthrough DNA editing-technology. This technology, called clustered regularly interspaced short palindrome repeats or CRISPR-Cas9, can alter any DNA, including DNA in embryos, meaning that changes can be passed to the offspring of the person that embryo becomes. Should we use gene editing technologies to change ourselves, our children, and future generations to come? The potential uses of CRISPR-Cas9 and other gene editing technologies are unprecedented in human history. By using these technologies, we eradicate certain dreadful diseases. Altering human DNA, however, raises enormously difficult questions. Some of these questions are about safety: Can these technologies be deployed without posing an unreasonable risk of physical harm to current and future generations? Can all physical risks be adequately assessed, and responsibly managed? But gene editing technologies also raise other moral questions, which touch on deeply held, personal, cultural, and societal values: Might such technologies redefine what it means to be healthy, or normal, or cherished? Might they undermine relationships between parents and children, or exacerbate the gap between the haves and have-nots? The broadest form of this second kind of question is the focus of this book: What might gene editing--and related technologies--mean for human flourishing? In the new essays collected here, an interdisciplinary group of scholars asks age--old questions about the nature and well-being of humans in the context of a revolutionary new biotechnology--one that has the potential to change the genetic make-up of both existing people and future generations. Welcoming readers who study related issues and those not yet familiar with the formal study of bioethics, the authors of these essays open up a conversation about the ethics of gene editing. It is through this conversation that citizens can influence laws and the distribution of funding for science and medicine, that professional leaders can shape understanding and use of gene editing and related technologies by scientists, patients, and practitioners, and that individuals can make decisions about their own lives and the lives of their families.

Isogenic Human Pluripotent Stem Cell Models of Cardiovascular Disease Associated Genetic Variation

Isogenic Human Pluripotent Stem Cell Models of Cardiovascular Disease Associated Genetic Variation Book
Author : Derek Tilghman Peters
Publisher : Unknown
Release : 2016
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The properties of human pluripotent stem cells (hPSCs) make them uniquely suited to address this challenge - they retain a normal human genome in culture, can be genetically modified, and can be differentiated into multiple cell types. The work presented in this thesis demonstrates the use of hPSCs and genome editing technology to generate human disease models in vitro. We developed a genome editing system optimized for hPSCs that can be used to efficiently generate hPSC lines with targeted genetic modifications. Modified and isogenic control hPSCs are then differentiated into a relevant cell type for phenotypic characterization. We applied this approach to investigate the functional effects of human genetic variation underlying plasma lipid concentrations.

Using Single Cell Epigenomic Analysis to Reveal Mechanisms of Complex Disease

Using Single Cell Epigenomic Analysis to Reveal Mechanisms of Complex Disease Book
Author : James Hocker
Publisher : Unknown
Release : 2022
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Complex diseases, and cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, are leading causes of morbidity and mortality worldwide. These diseases arise from interactions between lifestyle factors, environmental influences, and multiple disease associated genes. Efforts to identify the driving genes underlying complex diseases have culminated in genome-wide association studies (GWAS), which measure associations between common human sequence variants and disease phenotypes in large population cohorts. To date, GWAS have identified tens of thousands of sequence variants associated with cardiovascular diseases and a spectrum of other complex diseases. However, the vast majority of these variants reside in the noncoding regions of the genome, and do not directly disrupt protein-coding sequences in genes. Cis-regulatory elements (CREs) are noncoding sequences that regulate the expression levels of neighboring genes in a cell type-specific fashion. Observations that disease associated variants from GWAS are enriched in CREs led to the hypothesis that a major mechanism by which these variants influence disease is by disrupting the regulation of gene expression in specific cell types. However, we still lack comprehensive maps of CREs, not only in the cell types of the human heart, but also in the majority of tissues in the human body. The absence of such maps has posed a key challenge to discovery of the cell types through which disease-associated variants act and the interpretation of their detailed molecular mechanisms. These challenges, reviewed in Chapter 1, led me to ask the following questions which form the backbone of my thesis research: 1) how do individual human cell types utilize CREs to regulate gene expression, and 2) how do disease-associated noncoding sequence variants from GWAS influence cell type-specific gene regulation to cause disease? In this dissertation, I set out to address these questions in projects of progressively more expansive scope. First, in Chapter 2, I used single cell epigenomic and transcriptomic methods to define the regulation of gene expression by candidate CREs (cCREs) in nine cell types from the adult human heart. By localizing risk variants for cardiovascular diseases to these cCREs, I uncovered strong enrichments of variants associated with complex cardiovascular diseases in cCREs from individual cardiac cell types, such as atrial fibrillation (AF) variants in cardiomyocyte cCREs. Next, I examined the specific AF risk variants underlying these enrichments, linked them to putative target genes, and tested their molecular mechanisms in human iPSC derived cardiomyocytes using luciferase reporter assays and CRISPR-Cas9 mediated genome editing. Results from these experiments showed that a cardiomyocyte-specific enhancer containing noncoding AF risk variants is necessary for KCNH2 expression and regulation of action potential repolarization in cardiomyocytes. Using this work as a foundation, in Chapter 3, I next applied single cell epigenomic methods to 30 different tissue types from across the entire adult human body. Integrating these datasets with corresponding data from 15 fetal tissue types revealed the cell type-specificity of over 1 million cCREs in 222 distinct human cell types. Moving beyond cardiovascular diseases and cardiac cell types, I next localized risk variants from the spectrum of complex human diseases and traits to body wide maps of cCREs in human cell types. This analysis resulted in thousands of significant enrichments of risk variants for complex diseases in cCREs of specific cell types. To link specific variants to putative molecular functions, I created a framework that incorporates statistical fine mapping, target gene linkage, and measurements of transcription factor binding site disruption to yield candidate molecular functions for hundreds of distinct noncoding risk variants. I lastly highlight examples of specific variants that may disrupt the activity of cell type-specific cCREs to contribute to complex diseases. Finally, in Chapter 4 I summarize future directions of this research. First, I outline technological developments that will greatly enhance the utility of these data and frameworks for interpreting the functions of complex disease risk variants. Second, I describe ongoing work to use the healthy tissue datasets I generated as a springboard for uncovering cell type-specific gene regulatory programs in diseased human tissues, with a focus on ischemic heart failure.

Reprogramming the Genome CRISPR Cas based Human Disease Therapy

Reprogramming the Genome  CRISPR Cas based Human Disease Therapy Book
Author : Anonim
Publisher : Elsevier
Release : 2021-06-29
ISBN : 0323853234
Language : En, Es, Fr & De

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Book Description :

Reprogramming the Genome: CRISPR-Cas-based Human Disease Therapy, presents the collation of chapters written by eminent scientists worldwide. CRISPR-Cas9 is a key technology for targeted genome editing and regulation in a number of organisms including mammalian cells. It is a rapid, simple, and cost-effective solution. CRISPR-Cas system has recently gained much scientific and public attention. This volume covers CRISPR-Cas9 based mammalian genome editing, creating disease models, cancer therapy, neurological, heredity, blood disorders, defective gene correction, stem cells therapy, epigenetic modifications, patents, ethics, biosafety and regulatory issues challenges and opportunities. This book is a key source of information on mammalian genome editing available in a single volume. This book will be useful for beginners in mammalian genome editing and also students, researchers, scientists, policymakers, clinicians and stakeholders interested in genome editing in several areas. Offers basic understanding and a clear picture of mammalian genome editing through CRISPR-Cas systems Discusses how to create mammalian disease models, stem cell modification, epigenetic modifications, correction of defective gene in blood disorders, heredity, neurological disorders and many more Discusses the application of CRISPR-Cas9 systems in basic sciences, biomedicine, molecular biology, translational sciences, neurobiology, neurology, cancer, stem cells, and many more

Heritable Human Genome Editing

Heritable Human Genome Editing Book
Author : The Royal Society,National Academy of Sciences,National Academy of Medicine,International Commission on the Clinical Use of Human Germline Genome Editing
Publisher : National Academies Press
Release : 2021-01-16
ISBN : 0309671132
Language : En, Es, Fr & De

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Book Description :

Heritable human genome editing - making changes to the genetic material of eggs, sperm, or any cells that lead to their development, including the cells of early embryos, and establishing a pregnancy - raises not only scientific and medical considerations but also a host of ethical, moral, and societal issues. Human embryos whose genomes have been edited should not be used to create a pregnancy until it is established that precise genomic changes can be made reliably and without introducing undesired changes - criteria that have not yet been met, says Heritable Human Genome Editing. From an international commission of the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the U.K.'s Royal Society, the report considers potential benefits, harms, and uncertainties associated with genome editing technologies and defines a translational pathway from rigorous preclinical research to initial clinical uses, should a country decide to permit such uses. The report specifies stringent preclinical and clinical requirements for establishing safety and efficacy, and for undertaking long-term monitoring of outcomes. Extensive national and international dialogue is needed before any country decides whether to permit clinical use of this technology, according to the report, which identifies essential elements of national and international scientific governance and oversight.

Precision Medicine for Investigators Practitioners and Providers

Precision Medicine for Investigators  Practitioners and Providers Book
Author : Joel Faintuch,Salomao Faintuch
Publisher : Academic Press
Release : 2019-11-16
ISBN : 0128191791
Language : En, Es, Fr & De

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Book Description :

Precision Medicine for Investigators, Practitioners and Providers addresses the needs of investigators by covering the topic as an umbrella concept, from new drug trials to wearable diagnostic devices, and from pediatrics to psychiatry in a manner that is up-to-date and authoritative. Sections include broad coverage of concerning disease groups and ancillary information about techniques, resources and consequences. Moreover, each chapter follows a structured blueprint, so that multiple, essential items are not overlooked. Instead of simply concentrating on a limited number of extensive and pedantic coverages, scholarly diagrams are also included. Provides a three-pronged approach to precision medicine that is focused on investigators, practitioners and healthcare providers Covers disease groups and ancillary information about techniques, resources and consequences Follows a structured blueprint, ensuring essential chapters items are not overlooked

Genome Editing Applications in Animal Research

Genome Editing Applications in Animal Research Book
Author : Jun Song,Bradford Daigneault,Zhanjun Li,Huaqiang Yang
Publisher : Frontiers Media SA
Release : 2022-02-18
ISBN : 2889744426
Language : En, Es, Fr & De

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Book Description :

Download Genome Editing Applications in Animal Research book written by Jun Song,Bradford Daigneault,Zhanjun Li,Huaqiang Yang, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Reprogramming the Genome CRISPR Cas based Human Disease Therapy

Reprogramming the Genome  CRISPR Cas based Human Disease Therapy Book
Author : Anonim
Publisher : Academic Press
Release : 2021-06-12
ISBN : 0323853242
Language : En, Es, Fr & De

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Book Description :

Reprogramming the Genome: CRISPR-Cas-based Human Disease Therapy, presents the collation of chapters written by eminent scientists worldwide. CRISPR-Cas9 is a key technology for targeted genome editing and regulation in a number of organisms including mammalian cells. It is a rapid, simple, and cost-effective solution. CRISPR-Cas system has recently gained much scientific and public attention. This volume covers CRISPR-Cas9 based mammalian genome editing, creating disease models, cancer therapy, neurological, heredity, blood disorders, defective gene correction, stem cells therapy, epigenetic modifications, patents, ethics, biosafety and regulatory issues challenges and opportunities. This book is a key source of information on mammalian genome editing available in a single volume. This book will be useful for beginners in mammalian genome editing and also students, researchers, scientists, policymakers, clinicians and stakeholders interested in genome editing in several areas. Offers basic understanding and a clear picture of mammalian genome editing through CRISPR-Cas systems Discusses how to create mammalian disease models, stem cell modification, epigenetic modifications, correction of defective gene in blood disorders, heredity, neurological disorders and many more Discusses the application of CRISPR-Cas9 systems in basic sciences, biomedicine, molecular biology, translational sciences, neurobiology, neurology, cancer, stem cells, and many more

Stem Cells and Cardiovascular Diseases

Stem Cells and Cardiovascular Diseases Book
Author : Shijun Hu,Lei Ye,Mingtao Zhao,Feng Lan
Publisher : Frontiers Media SA
Release : 2022-03-17
ISBN : 2889747212
Language : En, Es, Fr & De

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Book Description :

Download Stem Cells and Cardiovascular Diseases book written by Shijun Hu,Lei Ye,Mingtao Zhao,Feng Lan, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Genome Plasticity in Health and Disease

Genome Plasticity in Health and Disease Book
Author : Anonim
Publisher : Academic Press
Release : 2020-04-08
ISBN : 0128178205
Language : En, Es, Fr & De

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Book Description :

Genome Plasticity in Health and Disease provides a fully up-to-date overview on genome plasticity and its role in human physiology and disease. Following an introduction to the field, a diverse range of chapters cover genomic and epigenomic analysis and the use of model organisms and genomic databases in studies. Specific molecular and biochemical mechanisms of genome plasticity are examined, including somatic variants, De Novo variants, founder variations, isolated populations dynamics, copy-number variations, mobile elements, DNA methylation, histone modifications, transcription factors, non-coding RNAs, telomere dynamics and RNA editing. Later chapters explore disease relevance for cancer, as well as cardiovascular, neuropsychiatric, inflammatory, and endocrine disease, and associated pathways for drug discovery. Examines the role of genome plasticity across a range of disease types, from cardiovascular disease, to cancer and neuropsychiatric disorders Adopts an interdisciplinary approach, with expert contributions across the spectrum of basic science and disease relevance to drug discovery

Clinical and Molecular Aspects of Cardiomyopathies On the road from gene to therapy An Issue of Heart Failure Clinics E Book

Clinical and Molecular Aspects of Cardiomyopathies  On the road from gene to therapy  An Issue of Heart Failure Clinics  E Book Book
Author : Giuseppe Limongelli
Publisher : Elsevier Health Sciences
Release : 2018-04-02
ISBN : 0323610471
Language : En, Es, Fr & De

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Book Description :

This issue of Heart Failure Clinics--edited by Drs. Giuseppe Limongelli, Sharlene Day, and Perry Elliott--will cover Clinical and Molecular Aspects of Cardiomyopathies: On the Road from Gene to Therapy. Topics include, but are not limited to, Epidemiology and Clinical aspects of Genetic Cardiomyopathies, Existing and New therapies, Gene editing and gene-based therapeutics, Controversies surrounding exercise in genetic cardiomyopathies, Genetic infiltrative cardiomyopathies, LV Noncompaction, Clinical presentation and natural history of hypertrophic cardiomyopathy in Rasopathies, and Moelcular basis and new treatments of cardiac diseases in Rasopathies.