More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
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We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
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Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
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Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
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\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8644",leadTitle:null,fullTitle:"Accounting and Finance - New Perspectives on Banking, Financial Statements and Reporting",title:"Accounting and Finance",subtitle:"New Perspectives on Banking, Financial Statements and Reporting",reviewType:"peer-reviewed",abstract:"Accounting and finance are common terms for users of financial information. Nowadays the reporting of financial as well as non-financial information of an entity, and efficiency in the banking system, are considered to be important issues by creditors, investors, and managers of financial markets.Over four sections this book addresses topics including national accounting standards and financial statement disclosure; foreign direct investment and the roles of accounting valuations and earnings management during the global financial crisis; and bankruptcy risk, banking efficiency, and debt restructuring in the United Nations General Assembly Resolution.",isbn:"978-1-83968-198-1",printIsbn:"978-1-83968-197-4",pdfIsbn:"978-1-83968-199-8",doi:"10.5772/intechopen.79593",price:119,priceEur:129,priceUsd:155,slug:"accounting-and-finance-new-perspectives-on-banking-financial-statements-and-reporting",numberOfPages:148,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"05150c3d097ed7178a67213166db89b6",bookSignature:"Reza Gharoie Ahangar and Can Öztürk",publishedDate:"December 18th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8644.jpg",numberOfDownloads:6883,numberOfWosCitations:1,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:9,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 18th 2018",dateEndSecondStepPublish:"July 9th 2018",dateEndThirdStepPublish:"September 7th 2018",dateEndFourthStepPublish:"November 26th 2018",dateEndFifthStepPublish:"January 25th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"91081",title:"Dr.",name:"Reza",middleName:null,surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar",profilePictureURL:"https://mts.intechopen.com/storage/users/91081/images/system/91081.jpg",biography:"Reza Gharoie Ahangar is a Ph.D. student in Decision Science with a minor in Economics and a teaching fellow and research assistant in G. Brint Ryan College of Business, University of North Texas, USA. He is a member of the American Finance Association (AFA), Decision Sciences Institute (DSI), Production and Operations Management Society (POMS), Institute for Operations Research and the Management Sciences (INFORMS), and Association of Scientists, Developers, and Faculties (ASDF). Mr. Ahangar is a teaching assistant at UNT for six years and has authored eight books and book chapters as well as several journal and conference publications in finance and business analytics, with more than forty technical publications. His research works are cited by the top 0.1% of most-read authors in academia. He serves as an editorial board member for several scientific journals. His current research interests include investment, forecasting, optimization, FinTech, and the application of artificial intelligence in financial areas.",institutionString:"University of North Texas",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of North Texas",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:{id:"280253",title:"Dr.",name:"Can",middleName:null,surname:"Ozturk",slug:"can-ozturk",fullName:"Can Ozturk",profilePictureURL:"https://mts.intechopen.com/storage/users/280253/images/system/280253.jpg",biography:"Dr. Can Öztürk is an associate professor of financial, international and comparative accounting at the Department of Management, Çankaya University, Ankara, Turkey. He received his first Bachelor’s in Banking and Finance (2001) from Bilkent University, his second Bachelor\\'s in Finance (2003) and Master’s in Business Administration (2004) from the University of Massachusetts Dartmouth, USA as well as his Ph.D. in Accounting and Finance in 2011 from Başkent University, Turkey. His primary research interests are IFRS, IFRS for SMEs, Financial Reporting Standards for Non-Publicly Accountable Entities, ISAs, and Corporate Social Responsibility Reporting. He has published several articles in prestigious journals at the national and international context such as Accounting in Europe, Accounting and Management Information Systems, Emerging Markets Journal and The World of Accounting Science. He speaks English and French in addition to Turkish.",institutionString:"Çankaya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Çankaya University",institutionURL:null,country:{name:"Turkey"}}},equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1416",title:"Public Finance",slug:"public-finance"}],chapters:[{id:"70035",title:"Introductory Chapter: Some Current Issues on Accounting and Finance",doi:"10.5772/intechopen.90190",slug:"introductory-chapter-some-current-issues-on-accounting-and-finance",totalDownloads:844,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Reza Gharoie Ahangar and Can Öztürk",downloadPdfUrl:"/chapter/pdf-download/70035",previewPdfUrl:"/chapter/pdf-preview/70035",authors:[{id:"91081",title:"Dr.",name:"Reza",surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar"},{id:"280253",title:"Dr.",name:"Can",surname:"Ozturk",slug:"can-ozturk",fullName:"Can Ozturk"}],corrections:null},{id:"65655",title:"National Accounting Standards in Turkey",doi:"10.5772/intechopen.84364",slug:"national-accounting-standards-in-turkey",totalDownloads:1262,totalCrossrefCites:3,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This study describes the accounting standards being implemented in Turkey. Uniform Accounting System and Uniform Chart of Accounts, Turkish Financial Reporting Standards (TFRS), and Financial Reporting Standards for Large- and Medium-Sized Enterprises (FRS for LMEs) are simultaneously applied in Turkey. TFRS are a direct translation of the International Financial Reporting Standards (IFRS). Enterprises that are subject to independent audit apply TFRS. FRS for LMEs is a financial reporting framework that is subject to independent audit and is valid for financial statements presented to general assemblies of enterprises that do not apply the TFRS. Enterprises that are not subject to independent audit apply Uniform Accounting System. Uniform Chart of Accounts is used by all these businesses. Despite these new practices, a revision has not been carried out in Uniform Chart of Accounts. Because of these applications, it is necessary to define the new accounts needed and to review Uniform Chart of Accounts. Banks, insurance and pension companies, finance companies, financial leasing and factoring companies, and asset management companies are required to use a different account plan despite the application of TFRS.",signatures:"Birsel Sabuncu",downloadPdfUrl:"/chapter/pdf-download/65655",previewPdfUrl:"/chapter/pdf-preview/65655",authors:[{id:"282962",title:"Dr.",name:"Birsel",surname:"Sabuncu",slug:"birsel-sabuncu",fullName:"Birsel Sabuncu"}],corrections:null},{id:"67509",title:"CSR Training and Financial Statement “Disclosure”: The Case of Italy",doi:"10.5772/intechopen.86688",slug:"csr-training-and-financial-statement-disclosure-the-case-of-italy",totalDownloads:898,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The objective of the chapter is to analyse the impact that CSR (corporate social responsibility) training had on non-financial information that is contained in financial statements following the EU directive 2014/95/EU and the Italian law: 254/2016. Literature review is based on institutional theory and social and environmental accounting as emancipatory tool to ameliorate the quality of life. The case analysed is the territory of Rimini, Italy. The case has been chosen because Rimini represents one of the most important concentrations within the hospitality and tourism industry in Europe. Another reason is that in the area of Rimini, 13 years ago, CSR training courses had been promoted for profit-making enterprises by the Chamber of Commerce along with public and private organisations. These training courses created a very important background for collocating the new EU directive regarding non-financial information that must necessarily be contained within the financial statements of enterprises. The objective of the chapter is to analyse the impact that the CSR training had on non-financial information that is contained in financial statements following the EU directive 2014/95/EU and Italian law: 254/2016.",signatures:"Maria-Gabriella Baldarelli",downloadPdfUrl:"/chapter/pdf-download/67509",previewPdfUrl:"/chapter/pdf-preview/67509",authors:[{id:"289002",title:"Prof.",name:"Maria Gabriella",surname:"Baldarelli",slug:"maria-gabriella-baldarelli",fullName:"Maria Gabriella Baldarelli"}],corrections:null},{id:"66881",title:"Nonlinear Effect of Financial Development and Foreign Direct Investment in Integration Economies Among ASEAN-5 Countries Following IFRS Adoption",doi:"10.5772/intechopen.86104",slug:"nonlinear-effect-of-financial-development-and-foreign-direct-investment-in-integration-economies-amo",totalDownloads:462,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter examines the role of financial development on foreign direct investment (FDI) inflows in ASEAN-5 countries over the period of 1980–2017. The ASEAN-5 countries include Malaysia, Thailand, Indonesia, Singapore, and the Philippines. The panel cointegration of second generation is used in order to address the existence of economic integration among ASEAN-5 as proven in cross-sectional dependency test. The results from fully modified ordinary least square (FMOLS) and cross-sectional dependency autoregressive distributed lag (CS-ARDL) consistently shows that the financial development has a nonlinear relationship with FDI of U-shape, whereby the financial development will benefit the FDI after it beyond the threshold point at 70% of total GDP. Investors will make decision based on the financial status as shown in the financial accounting report, whereby the quality of financial accounting representing transparent information that leads on reducing asymmetric information between investor and the financial institutions in host countries. In addition, the causality analysis based on panel vector error correction model (VECM) confirms the presence of both long-run relationship and short-run dynamic among FDI, financial development, consumer price index, and real gross domestic product per capita.",signatures:"Elya Nabila Abdul Bahri and Nor Hakimah Haji Mohd Nor",downloadPdfUrl:"/chapter/pdf-download/66881",previewPdfUrl:"/chapter/pdf-preview/66881",authors:[{id:"283039",title:"Dr.",name:"Elya Nabila",surname:"Abdul Bahri",slug:"elya-nabila-abdul-bahri",fullName:"Elya Nabila Abdul Bahri"},{id:"292430",title:"Dr.",name:"Nor Hakimah",surname:"Haji Mohd Nor",slug:"nor-hakimah-haji-mohd-nor",fullName:"Nor Hakimah Haji Mohd Nor"}],corrections:null},{id:"69473",title:"The Roles of Accounting Valuations and Earnings Management in the Survivorship of Technology Firms during the Global Financial Crisis",doi:"10.5772/intechopen.85395",slug:"the-roles-of-accounting-valuations-and-earnings-management-in-the-survivorship-of-technology-firms-d",totalDownloads:703,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This study examines the survivorship of technology firms listed on the NASDAQ market during the immediate and post-2008 global financial crisis period. Underpinned by contingency theory, this study demonstrates the varying roles of accounting valuation and earnings management metrics in the technology industry. Findings in this chapter show during the global financial crisis periods, technology firms have greater survivorships when they are undervalued, and possess a lesser degree of discretionary earnings (DA). The DA factor is a double-edged sword for technology firms since it has positive and negative effects on the returns and survivorships, respectively. The research and development (R&D) variable remains a positive component for both returns and survivorships of these firms.",signatures:"Oliver Neoh and Matthias Nnadi",downloadPdfUrl:"/chapter/pdf-download/69473",previewPdfUrl:"/chapter/pdf-preview/69473",authors:[{id:"289136",title:"Dr.",name:"Matthias",surname:"Nnadi",slug:"matthias-nnadi",fullName:"Matthias Nnadi"},{id:"289137",title:"Mr.",name:"Oliver",surname:"Neoh",slug:"oliver-neoh",fullName:"Oliver Neoh"}],corrections:null},{id:"66043",title:"Banks Financial State Analysis and Bankruptcy Risk Forecasting with Application of Fuzzy Neural Networks",doi:"10.5772/intechopen.82534",slug:"banks-financial-state-analysis-and-bankruptcy-risk-forecasting-with-application-of-fuzzy-neural-netw",totalDownloads:822,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The problem of banks bankruptcy risk forecasting under uncertainty is considered. For its solution, the application of computational intelligence methods fuzzy neural networks ANFIS and TSK and inductive modeling method FGMDH was suggested and explored. Experimental investigations were carried out and estimation of the efficiency of the suggested methods was performed at the problems of bankruptcy risk forecasting for Ukrainian and leading European banks. The efficiency comparison with classic statistical methods such as ARMA, logit, and probit models was fulfilled. The comparative experiments with rating system CAMELS and matrix method were carried out. In general, the comparative analysis had shown that fuzzy forecasting methods and techniques give better results than conventional crisp methods for forecasting bankruptcy risk. On the whole, the conclusions of experiments with European banks completely confirmed the conclusions of experiments with Ukrainian banks. But at the same time, the crisp methods are more simple in implementation and demand less time for their adjustment. The set of informative bank financial factors for bankruptcy risk forecasting was determined and estimated.",signatures:"Yuriy Zaychenko, Michael Zgurovsky and Galib Hamidov",downloadPdfUrl:"/chapter/pdf-download/66043",previewPdfUrl:"/chapter/pdf-preview/66043",authors:[{id:"67789",title:"Prof.",name:"Michael",surname:"Zgurovsky",slug:"michael-zgurovsky",fullName:"Michael Zgurovsky"},{id:"268119",title:"Prof.",name:"Yuriy",surname:"Zaychenko",slug:"yuriy-zaychenko",fullName:"Yuriy Zaychenko"}],corrections:null},{id:"65768",title:"The Colombian Banking Sector: Analysis from Relative Efficiency",doi:"10.5772/intechopen.84585",slug:"the-colombian-banking-sector-analysis-from-relative-efficiency",totalDownloads:1056,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The banking sector is that sector of the modern economy that is primarily called upon to play the important role of intermediation between the surplus agents and the deficit agents. Based on this fact, this research presents and analyzes the behavior of banks in Colombia since 2002 and up to 2016 (15 years) through the application of data envelopment analysis, a nonparametric methodology of advanced linear programming, which generates a single efficiency indicator for each unit studied in each period, optimizing multiple resources (inputs) and multiple products (outputs). One aspect of the results shows that for the year 2014, 71% of the banks were efficient, this being the highest result within the period studied.",signatures:"Gloria Rodriguez-Lozano",downloadPdfUrl:"/chapter/pdf-download/65768",previewPdfUrl:"/chapter/pdf-preview/65768",authors:[{id:"266828",title:"Ph.D.",name:"Gloria",surname:"Rodriguez-Lozano",slug:"gloria-rodriguez-lozano",fullName:"Gloria Rodriguez-Lozano"}],corrections:null},{id:"66626",title:"Sustainability in Indebtedness: A Proposal for a Treaty-Based Framework in Sovereign Debt Restructuring",doi:"10.5772/intechopen.82470",slug:"sustainability-in-indebtedness-a-proposal-for-a-treaty-based-framework-in-sovereign-debt-restructuri",totalDownloads:838,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The debate concerning reforms in sovereign debt restructuring (SDR) ranges from those which maximize flexibility (e.g. adoption of clauses in debt contracts) to those which maximize uniformity and predictability (e.g. enacting a fixed framework similar to a domestic bankruptcy regime). This paper proposes that the principles of SDR in the United Nations General Assembly Resolution 69/319 be broadly codified into a treaty. This includes the principle of sustainability which emphasizes “inclusive growth and sustainable development” of stakeholders in SDR. In the current unsystematized regime of SDR, this proposal seeks to bridge the value of flexibility in ex post negotiations and the values of uniformity and predictability in ex ante rules under fixed bankruptcy regimes.",signatures:"Maximo Paulino T. Sison III",downloadPdfUrl:"/chapter/pdf-download/66626",previewPdfUrl:"/chapter/pdf-preview/66626",authors:[{id:"264901",title:"Mr.",name:"Maximo Paulino Iii",surname:"Sison",slug:"maximo-paulino-iii-sison",fullName:"Maximo Paulino Iii Sison"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8148",title:"Investment Strategies in Emerging New Trends in Finance",subtitle:null,isOpenForSubmission:!1,hash:"3b714d96a68d2acdfbd7b50aba6504ca",slug:"investment-strategies-in-emerging-new-trends-in-finance",bookSignature:"Reza Gharoie Ahangar and Asma Salman",coverURL:"https://cdn.intechopen.com/books/images_new/8148.jpg",editedByType:"Edited by",editors:[{id:"91081",title:"Dr.",name:"Reza",surname:"Gharoie Ahangar",slug:"reza-gharoie-ahangar",fullName:"Reza Gharoie Ahangar"}],equalEditorOne:{id:"206443",title:"Prof.",name:"Asma",middleName:null,surname:"Salman",slug:"asma-salman",fullName:"Asma Salman",profilePictureURL:"https://mts.intechopen.com/storage/users/206443/images/system/206443.png",biography:"Professor Asma Salman is a blockchain developer and Professor of Finance at the American University in the Emirates, UAE. An Honorary Global Advisor at the Global Academy of Finance and Management, USA, she completed her MBA in Finance and Accounting and earned a Ph.D. in Finance from an AACSB member, AMBA accredited, School of Management at Harbin Institute of Technology, China. Her research credentials include a one-year residency at the Brunel Business School, Brunel University, UK. Prof. Salman also served as the Dubai Cohort supervisor for DBA students under the Nottingham Business School, UK, for seven years and is currently a Ph.D. supervisor at the University of Northampton, UK, where she is a visiting fellow. She also served on the Board of Etihad Airlines during 2019–2020. One of her recent articles on “Bitcoin and Blockchain” gained wide visibility and she is an active speaker on Fintech, blockchain, and crypto events around the GCC. 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1. Introduction
Intracellular and blood potassium levels have crucial effects on cardiovascular system homeostasis. At the most fundamental level, the potassium concentration gradient across cardiac muscle cell (cardiomyocyte) cell membranes is a chief determinant of cardiomyocyte resting membrane potentials. Indeed, disruptions to this concentration gradient (e.g. via increasing or decreasing extracellular blood potassium levels) can lead to altered cardiomyocyte contractility and excitability. Potassium is also vasoactive, with different effects at different extracellular concentrations. At low (5-8 mM) to moderate (8-16 mM) extracellular levels, potassium relaxes the smooth muscle in blood vessel walls by promoting hyperpolarization of vascular smooth muscle. However, at higher levels (16-25 mM and above) (e.g. cardioplegic concentrations), potassium promotes vasoconstriction by facilitating depolarization. Moreover, potassium is released by vascular endothelial cells in response to various chemical mediators and shear stress, thereby contributing to the action of endothelium-derived hyperpolarizing factor [1]. For all of these reasons and more, keeping track of daily potassium intake is often recommended as a lifestyle modification for chronic cardiovascular diseases such as hypertension.
Harnessing the pivotal role of potassium in cardiovascular physiology has proved quite useful for cardiovascular surgery, namely in the form of hyperkalemic (high potassium) cardioplegia. Indeed, throughout the past several decades, a large body of research has testified to the ability of externally administered hyperkalemic solutions to arrest cardiac contractility [2]. This, in conjunction with the development of cardiopulmonary bypass (CPB, also known as the “heart-lung machine”), revolutionized cardiac surgery [3]. These days, many highly invasive procedures like coronary artery bypass grafting are routine with minimal risk of postoperative mortality.
However, hyperkalemic cardioplegia is not without its consequences. Hyperkalemic cardioplegia and reperfusion following CPB have been associated with perioperative and postoperative tissue damage and microvascular dysfunction across several different vascular beds. Moreover, hyperkalemic cardioplegia is also associated with postoperative myocardial dysfunction and reduced cardiac output. Furthermore, blood potassium abnormalities after hyperkalemic cardioplegia-reperfusion, chiefly hypokalemia (but also hyperkalemia, to a lesser degree) are common postoperative challenges in the cardiac ICU. Both abnormalities significantly elevate the risk of arrythmias and, if not managed properly, cardiac arrest and sudden death.
This chapter will discuss the basics of potassium cardioplegia with an emphasis on clinical relevance, beginning with a brief history. Subsequent sections will elaborate on the basic physiology, before considering several perioperative and postoperative adverse effects of hyperkalemic cardioplegia. When possible, information about treatment and clinical management is included. The chapter will conclude with a brief mention of up-and-coming alternatives to hyperkalemic cardioplegia.
2. Potassium and cardiac surgery
2.1 Brief history of potassium cardioplegia
As early as the late 1800s, physiologists were starting to become aware of the ability of potassium compounds to arrest cardiac contractility, beginning with individuals like Sidney Ringer who observed that potassium chloride froze the heart in diastole and calcium stimulated the heart during systole [2]. Moving into the start of the 20th century, further investigations revealed associations between high serum potassium and cardiac arrest following ventricular fibrillation; studies also revealed associations between cardioplegia and restoration of sinus rhythm following coronary artery administration of potassium chloride solution and subsequent washout [2]. However, in most of these cardioplegic experiments (often conducted in dogs), refractory ventricular fibrillation and post-procedure reperfusion damage to the myocardium limited discussion of the clinical usefulness of these findings.
During the 1950s, British physician Dennis Melrose hypothesized that the problem with potassium chloride cardioplegia was chloride; therefore, he created a cardioplegic solution using potassium citrate, and tested it on a canine model of cardiopulmonary bypass [4]. Injection of the “Melrose solution”, of potassium citrate plus warm oxygenated whole blood in a 9:1 blood:potassium ratio, into the aortic roots of hypothermic dogs, produced near-immediate cardiac arrest. Reperfusion and washout of cardioplegic solution resulted in restoration of heart function to pre-procedure levels [2]. Within a few years, the Melrose group successfully induced potassium citrate cardioplegia in humans.
Unfortunately, future studies would reveal that in many cases, the Melrose potassium citrate solution still produced post-cardioplegia ventricular fibrillation and myocardial dysfunction [5]. This led to a general pause in clinical application of potassium cardioplegia between the 1960s and early 1980s, in favor of other options mostly involving induction of hypothermic cardiac arrest, which turned out to be no better with respect to postoperative damage than the Melrose solution.
Eventually, research into techniques for potassium cardioplegia would pick up again, and the result would be development of novel solutions for cardioplegia and intraoperative organ preservation. Numerous studies in animal models have validated the principles of diastolic cardiac arrest due to depolarizing potassium cardioplegia [2, 3, 6, 7, 8, 9, 10]. In addition, invention and refinement of heart-lung machines to accompany cardioplegia in the operative room (CPB) opened many new possibilities for cardiac surgery. Today, potassium cardioplegia is an integral tool for cardiac surgeons performing a variety of highly invasive procedures such as coronary artery bypass grafting and aortic valve replacements.
2.2 Types and techniques of potassium cardioplegia
Despite variability in composition, delivery, and temperature, most cardioplegic solutions in use today involve some level of potassium chloride as the main inducer of cardiac arrest, along with ions such as magnesium, low-dose calcium and bicarbonate, the latter of which is particularly important for controlling solution pH [6]. The “original” hyperkalemic cardioplegic solution was the Melrose formula of the 1950s that was discussed earlier, consisting of potassium citrate and warm blood in a 9:1 blood:potassium ratio. However, due to the high incidence of postoperative complications including ventricular fibrillation, this solution is no longer in major clinical use.
2.2.1 Crystalloid vs. blood
In general, cardioplegic solutions fall under two broad umbrellas: crystalloid vs. blood, and warm vs. cold (Table 1). Two crystalloid cardioplegic solutions worth noting are the Custodiol (also known as Bretschneider) and St. Thomas solutions [7]. The St. Thomas solution, introduced first by Hearse and colleagues in 1975, is an example of a short acting cardioplegic solution involving potassium chloride concentrations between 10 and 30 mM [8]. In general, the St. Thomas solution requires repeat dosing, roughly every 20 minutes, to sustain cardioplegia for long durations [7, 9]. Furthermore, myocardial acidosis has been noted between doses of St. Thomas solution [10].
St. Thomas Cardioplegia
Custodiol Cardioplegia
Del Nido Cardioplegia
Buckberg Cardioplegia
Warm Calafiore Cardioplegia (one variant)
K+
16 mM
9 mM
26 mM
Cold induction: 36 mM Maintenance: 36 mM Reperfusion: 15 mM
18–20 mM for inducing arrest, repeat delivery every 20 min with decreasing K concentrations
Ca
1.2 mM
0.015 mM
1.3 mM
Mg
16 mM
4 mM
2 g of 50% magnesium sulfate
15.5 mM
Na
110 mM
15 mM
NaHCO3
10 mM
13 mM
Other Components
18 mM Histidine hydrochloride 18 mM histidine 2 mM tryptophan 30 mM mannitol 1 mM potassium hydrogen 2-ketoglutarate
13 mL of 1% lidocaine 3.2 g/L of 20% mannitol
Cold Induction: 392 mL 5% dextrose, 50 mL 0.3 M tromethamine, 30 mL citrate–phosphate-2-dextrose Maintenance: 798 mL 5% dextrose, 123 mL 0.3 M tromethamine, 61 mL citrate–phosphate-2-dextrose Reperfusion: 26 mL 50% dextrose; 56 mL 0.3 M tromethamine; 113 mL citrate–phosphate-2-dextrose 62.5 mL glutamate/aspartate
500 mL 5% dextrose 4 mM tris(hydroxymethyl)aminomethane Core body temperature maintained at 37 degrees Celsius
Blood vs. Crystalloid
Crystalloid
Crystalloid
4:1 crystalloid: blood ratio
4:1 crystalloid: blood ratio
Normothermic blood
Table 1.
Composition of common potassium-based cardioplegic solutions.
In contrast, the Custodiol solution is a form of long acting, single dose cardioplegia consisting primarily of potassium chloride, sodium chloride, and magnesium sulfate as the chief electrolytes [11]. Additional components of the Custodiol solution include tryptophan (membrane stabilization) and histidine buffer (to maintain pH and buffer against byproducts of anaerobic glycolysis that build up during cardioplegia). Curiously, the relatively low levels of potassium (9 mM) and sodium (15 mM) in Custodiol appear to induce cardioplegia through a form of hyperpolarized arrest as opposed to depolarized arrest, unlike most other potassium cardioplegic solutions that have potassium concentrations in the range of 16-36 mM and sodium concentrations in the range of 10-110 mM (see Table 1 for detailed solution ion concentrations).
The general rationale for blood-based cardioplegia has centered on the theory that cardioplegic solutions containing blood are more “physiologic” than crystalloid solutions. For example, blood can support aerobic respiration and may be able to preserve normal myocardial metabolism during surgery. Therefore, blood cardioplegia may reduce the negative consequences of prolonged ischemia during CPB [11]. However, insufficient evidence exists currently to verify that hypothesis, and so any purported advantages of blood over crystalloid cardioplegia are for the time being mainly speculative.
Three hyperkalemic cardioplegic solutions in clinical use that contain blood are the Del Nido, Buckberg, and Calafiore solutions. The Del Nido solution uses a crystalloid:blood ratio of 4:1, and like the Custodiol solution is a long-acting cardioplegic solution, with one dose of 20 ml/kg providing myocardial protection for up to 60–90 minutes [7, 12]. Chief ionic ingredients include potassium chloride for rapid depolarized arrest, sodium bicarbonate to scavenge protons and buffer intracellular pH, and magnesium to block calcium channels and prevent intracellular calcium accumulation during cardioplegic arrest, thereby promoting postoperative myocardial recovery [12, 13]. Lidocaine in the Del Nido solution acts as a sodium channel blocker to mitigate against the sodium “window current” and reduce intracellular sodium accumulation [14].
Buckberg’s cardioplegia is a dextrose and saline-based solution that, similar to the Del Nido solution, consists of a crystalloid:blood ratio of 4:1 [15]. Other components include potassium chloride as the primary depolarizing agent, a tromethamine buffer, and citrate phosphate double dextrose to serve as a calcium chelator. However, unlike the Del Nido solution, Buckberg cardioplegia must be given as three separate formulations, some of which must be administered in multiple doses [15]. First, an induction solution stops the heart, and additional infusions of induction solution must be given every 15 to 20 minutes throughout the procedure. Second, a maintenance solution must be administered to sustain cardiac arrest and provide oxygen and nutrients to the cardiomyocytes. Finally, a reperfusion solution containing glutamate and aspartate is administered prior to removal of the aortic cross clamp to provide the heart with nutrients prior to restarting myocardial contractions.
Calafiore cardioplegia differs from Buckberg and Del Nido in that blood forms the sole foundation of Calafiore cardioplegic solution [16]. Indeed, the original rational proposed by Calafiore et al. was that blood alone, without any crystalloid component, contained everything necessary to prevent ischemia–reperfusion damage. Therefore, simply administering a cardioplegic solution consisting of blood plus extra potassium would be enough to safely stop and later, restart the heart [16]. Moreover, unlike most other forms of cardioplegia in use, the original Calafiore solution was normothermic throughout administration; however, some subsequent variations of Calafiore cardioplegia have used cold blood [16, 17].
2.2.2 Warm vs. cold
Most current methods for administering cardioplegic solutions involve cold cardioplegia, most often cold crystalloid solutions delivered after reducing core body temperature to hypothermic levels [18]. For example, the induction and maintenance solutions for Buckberg cardioplegia are delivered at 4 degrees Celsius after cooling core temperature to below 30 degrees Celsius, with reperfusion solution delivered at 37 degrees Celsius [15]. Similarly, del Nido and Custodiol cardioplegia are often given at 4 degrees Celsius after induction of systemic hypothermia [15, 19].
This practice stems from experimental evidence suggesting that mild hypothermia can protect the myocardium from ischemic damage during cardioplegia [20]. Hypothermia reduces the basal metabolic rate of the heart, which in turn reduces oxygen consumption—an effect augmented by potassium-induced arrest during hyperkalemic cardioplegia [21]. A variety of potential mechanisms may be at play. In animal models of cardiac arrest, mild hypothermia (32–35 degrees Celsius) has been shown to reduce post-arrest infarct size, possibly through various signal transduction pathways, such as Akt and mTOR signaling, both of which are altered during the course of hypothermia [20]. Another potential cardioprotective mechanism of hypothermia may be reduced phosphorylation of various mitogen activated protein kinases (MAPK) like ERK1/2 that normally activate pro-inflammatory mediators like COX-2 (arachidonic acid metabolism) [18]. In general, many details concerning mechanisms of hypothermic myocardial protection during cardioplegia remain to be elucidated.
However, cold hyperkalemic cardioplegia may also inhibit myocardial enzymes that are important for the metabolic and functional recovery of the heart after surgery [22, 23]. Moreover, sustained systemic hypothermia (especially at temperatures below 20 degrees Celsius) during cardiac surgery has also been associated with ventricular fibrillation after rewarming [21]. Given these negative consequences, an increasing amount of attention has been given to the possibility of warm hyperkalemic cardioplegia, primarily warm blood hyperkalemic cardioplegia. Unlike cold hyperkalemic cardioplegic solutions, warm cardioplegic solution is typically administered at between 30 and 35 degrees Celsius under normothermic, as opposed to hypothermic, CPB [24]. Potential advantages of warm blood hyperkalemic cardioplegia over cold crystalloid may include improved myocardial restoration, reduced intracellular swelling, improved membrane stabilization, and reduced hypoxic red blood cell deformation [25].
Of course, warm hyperkalemic cardioplegia is not without its own consequences. Some studies have reported increased likelihoods of perioperative strokes and encephalopathy [26]. Moreover, warm hyperkalemic cardioplegia may contribute to vasodilation during cardiopulmonary bypass, requiring increased use of alpha agonists during operation to maintain stable arterial perfusion pressures [25]. There are also several variations of warm cardioplegia; one common technical variant is “hot shot” cardioplegia, which involves warm induction and subsequent cold cardioplegia, followed by a warm reperfusion [27].
Comparing the effectiveness of warm vs. cold hyperkalemic cardioplegia remains an inconclusive subject of intense debate. A meta-analysis by Fan et al., reported no differences between length of stay, stroke incidence, and atrial fibrillation between patients undergoing warm vs. cold cardioplegia [28]. However, warm cardioplegia correlated with better postoperative cardiac indices and lower peak creatine kinase MB concentrations than cold cardioplegia [28]. The latter findings, along with reduced postoperative cardiac troponin levels, have been replicated in other studies [29, 30]. Meanwhile, other studies comparing warm blood and cold crystalloid hyperkalemic cardioplegia do not show significant differences with respect to perioperative myocardial infarction and low cardiac output syndrome [31].
2.2.3 Anterograde vs. retrograde
In general, administration of hyperkalemic cardioplegic solution can be done in either retrograde or anterograde fashion. Prior to both, IV heparin is administered, and the patient’s core body temperature is lowered to hypothermic levels, after which the aortic cross-clamp is placed and cardiopulmonary bypass is initiated [7]. Anterograde cardioplegia refers to delivering cardioplegic solution through a cannula inserted just proximal to the aortic cross-clamp. From there, the solution can flow into the left and right coronary arteries that supply the myocardium [32]. With anterograde cardioplegia, arrest usually occurs within 30 to 60 seconds. Retrograde cardioplegia may be considered in patients with complications such as severe coronary artery damage (e.g. severe stenosis) or aortic valve damage. Unlike anterograde administration, in retrograde administration the cardioplegia catheter is inserted into the coronary sinus from the right atrium, and solution is injected at a lower pressure (given the lower tolerance of the coronary sinus walls to turbulent flow) to avoid coronary sinus perforation [32].
2.3 Physiology of potassium cardioplegia during cardiac surgery
2.3.1 Physiology of cardiac muscle contraction
Under physiological circumstances, the cardiomyocyte resting membrane potential is largely determined by two key factors: action of the sodium-potassium ATPase, and the high resting permeability of cardiomyocyte cell membranes to potassium [33]. First, the sodium-potassium ATPase hydrolyzes ATP to continuously pump potassium into the cell and sodium out of the cell, with a relative ratio of 3Na out/2 K in per molecule of ATP. Because it is the primary ion pump active while the cell is at rest, the sodium-potassium ATPase plays a critical role in generating the characteristic sodium and potassium electrochemical gradients across the cardiomyocyte cell membrane (high potassium and low sodium inside the cell relative to out). Second, at rest the cardiomyocyte cell membrane is most permeable to potassium while being relatively impermeable to other ions. This results in a resting membrane potential for cardiomyocytes that is close to the Nernst equilibrium potential for potassium, roughly −85 to -90 mV.
During cardiac muscle contraction, sinoatrial node stimulation induces a transient increase in the resting membrane potential of cardiomyocytes, which in turn opens voltage-gated sodium channels once the membrane potential surmounts -65 mV. Due to the high inward ion driving force on sodium (based on the considerable difference between the Nernst potential for sodium and the resting membrane potential), sodium ions flow through the sodium channels into the cardiomyocyte and further depolarize the cell until it reaches about 20 mV. At this point, sodium channels inactivate and L-type voltage gated calcium channels take over the maintenance of the action potential, allowing influx of calcium ions and producing the classic plateau depolarization of cardiac ventricular action potentials. Eventually, as calcium channels close and membrane potential begins to dip, delayed rectifier potassium channels open and restore membrane potential to the resting state. By this point, enough calcium has entered the cardiomyocyte to promote calcium-induced calcium release from intracellular calcium stores in the cardiomyocyte sarcoplasmic reticula, allowing muscle contraction to occur.
2.3.2 Physiology of potassium cardioplegia
Extracellular hyperkalemia is the core principle underpinning most warm blood and cold crystalloid cardioplegic solutions. Essentially, administration of hyperkalemic solution takes advantage of the pivotal role of the potassium electrochemical gradient in determining cardiomyocyte resting membrane potential in order to elevate the resting membrane potential to a less negative value than typical baseline level. For example, physiologic extracellular potassium levels are often in the range of 3.5–5 mM, producing a resting membrane potential around -85 mV. During cardiac surgery involving cardioplegia, hyperkalemic solutions often raise extracellular potassium to the range of 10-40 mM (often midway in this range, around the 25 mM level), elevating cardiomyocyte resting membrane potentials to anywhere between −65 to -40 mV [34]. Arresting cardiomyocytes at this new range of elevated membrane potentials promotes fast sodium channel inactivation, thereby blocking myocardial action potential conduction. It also blocks repolarization, which is why hyperkalemic cardioplegia induces what is called “depolarized arrest.” Finally, it is important to note that cardioplegic arrest also significantly reduces cardiomyocyte oxygen consumption in a manner reminiscent of how severe ischemia depletes cellular ATP reserves [33].
2.4 Side effects of high potassium cardioplegia
2.4.1 Myocardial calcium loading
Despite its clinical usefulness in reversibly arresting the heart during cardiac surgery, sustained depolarized hyperkalemic cardioplegia is not without some negative perioperative consequences. First, while most voltage-gated “fast” sodium channels are inactivated at membrane potentials above -50 mV (a frequent target cardiomyocyte membrane potential for potassium cardioplegia), resulting in generally poor membrane sodium conductance, not all sodium channels are inactivated. Moreover, during hyperkalemic cardioplegia the ion driving force on sodium is still quite high, even at the new depolarized cell membrane potentials. Ultimately, this situation produces a small but significant sodium influx into cardiomyocytes through the small fraction of sodium channels that remain open during potassium cardioplegia, a phenomenon known as the sodium “window current” [35].
Similarly, ATP depletion and reduced myocardial oxygen consumption during hyperkalemic cardioplegia leads to myocardial ischemia. Ischemia forces myocardial cells to resort to anaerobic glycolysis for energy production, which generates lactate as a byproduct. Increasing lactate levels in cardiomyocytes produces a metabolic acidosis and promotes increased activity of the H+/Na antiporter to move protons out of the cells at the expense of bringing in more sodium [36]. Finally, the combination of high extracellular potassium, intracellular acidosis, and hypothermia due to cold cardioplegic solution inhibits action of the sodium-potassium ATPase, which further facilitates the buildup of intracellular sodium [34].
Note that -50 mV is also in the vicinity of the reversal potential of the sodium/calcium exchanger [37, 38]. Under normal circumstances, the sodium/calcium exchanger moves 3 Na in for every 1 Ca moved out of the cell. However, due to the sodium window current and depolarized arrest in hyperkalemic cardioplegia, the sodium/calcium exchanger eventually begins operating in reverse, moving 3 Na out for every 1 Ca in, producing a so-called calcium “window current.” Moreover, if the hyperkalemic cardioplegic solution holds cardiomyocyte membrane potentials above -50 mV, e.g. at around -40 mV, then voltage-gated slow calcium channels will begin to activate, causing further calcium influx [39]. All of these reasons help explain why many hyperkalemic cardioplegic solutions in clinical practice are also hypocalcemic relative to physiological extracellular calcium levels (or contain calcium channel blockers), to attempt to mitigate the severity of myocardial calcium loading [34].
Cytosolic calcium loading during hyperkalemic cardioplegia contributes to cardiomyocyte damage through several mechanisms [40]. Enhanced activation of calcium dependent proteases and lipases (e.g. phospholipases) contributes to plasma membrane phospholipid degradation, ultrastructural changes in the sarcolemmal membrane, and accumulation of pathological catabolic byproducts. Enhanced activation of calcium-dependent ATPases accelerates depletion of intracellular ATP stores that have already been lowered following hypothermic arrest. This further perturbs cardiomyocyte sarcolemmal calcium transport channels that rely on ATP to maintain intracellular calcium homeostasis. Moreover, hypoxia during hyperkalemic cardioplegia increases mitochondrial calcium uptake via reversal of mitochondrial sodium/calcium exchangers in a manner akin to reversal of cardiomyocyte cell membrane sodium/calcium exchangers [41].
Mitochondria can only endure so much calcium uptake before the onset of irreversible damage. Indeed, following reperfusion after hyperkalemic cardioplegia arrest, mitochondria exhibit increased oxygen free radical production and reduced superoxide dismutase activity, indicative of heightened oxidative stress [41]. Sustained oxidative stress can lead to opening of mitochondrial permeability transition pores (MPTP), which promote mitochondrial swelling and mitochondrial membrane rupture. An assortment of mitochondrial enyzmes and molecules, such as cytochrome c, leak out into the cytosol through the MPTPs [41]. Cytochrome c is implicated in intrinsic apoptotic pathways through activation of cytosolic caspases and subsequent formation of myocardial apoptosomes [41].
2.4.2 Myocardial apoptosis
Myocardial apoptosis during hyperkalemic cardioplegic ischemia–reperfusion merits further consideration for two major reasons. First, several studies have shown associations between hyperkalemic cardioplegic arrest and endothelial cell and cardiomyocyte apoptosis [42, 43, 44]. Second, several independent pathways of myocardial cell injury converge on apoptosis. Examples include mitochondrial oxidative stress and activation of an intrinsic apoptotic pathway (introduced earlier), or an extrinsic pathway driven by elevated humoral factors such as Fas or TNF-alpha acting on pro-apoptosis cell membrane receptors [44, 45]. Both intrinsic and extrinsic pathways converge upon a similar final common pathway that is chiefly regulated by two key protein groups: the Bcl-2 and cysteine protease caspase families [46, 47].
Within the Bcl-2 family, two proteins are particularly significant: Bcl-2 itself, and Bad. The former is anti-apoptotic while the latter is pro-apoptotic. Phosphorylation inhibits Bad, blocking it from inactivating Bcl-2 [48]. Farther downstream in apoptotic signaling, cleavage of caspase 3 and poly ADP-ribose polymerase (PARP) is essential for ensuring final progression towards apoptosis. Meanwhile, apoptosis may also proceed via a caspase-independent pathway involving release of the mitochondrial flavoprotein apoptosis-inducing factor (AIF) from the mitochondria into the cytosol through MPTPs [49, 50].
A possible framework for understanding myocardial apoptosis after hyperkalemic CPB is as follows [48]. Activation of the intrinsic (mitochondrial) pathway leads to increased Bad activation/decreased Bcl-2 activation, which initiates the caspase cascade. Activation of the extrinsic pathway bypasses Bcl-2/Bad to directly activate the caspase cascade. As more and more caspases become activated, eventually terminal caspases, such as caspase 3, will be cleaved, leading to PARP cleavage. By this point, apoptosis has been irreversibly induced; DNA fragmentation and cell death quickly follow. In contrast, AIF translocation from the mitochondria to the cytosol may directly activate downstream/terminal caspases, bypassing initial/intermediary constituents of the caspase cascade.
Studies have shown that caspase 3 cleavage and Bcl-2/Bad phosphorylation are significantly increased in myocardial tissue following hyperkalemic cold-blood cardioplegia and reperfusion, even as total protein levels do not change [48]. Meanwhile, myocardial AIF levels increase slightly, accompanied by a trend towards nuclear translocation, consistent with a model of AIF induced chromatin condensation and DNA fragmentation as a mechanism of cell injury [48]. Note that both pro-apoptotic (e.g. caspase 3) and anti-apoptotic (e.g. phosphorylated Bad) mediators are activated—nevertheless, given the downstream terminal position of caspase 3, the overall balance in myocardial cells appears to be tipped in favor of pro-apoptotic signaling.
Different formulations of hyperkalemic cardioplegia (e.g. cold crystalloid, warm blood, etc.) may exhibit differing degrees of myocardial protection and prevention of apoptosis. Indeed, evidence exists suggesting that cold blood hyperkalemic cardioplegia is superior to warm blood, warm crystalloid, and cold crystalloid cardioplegia, in terms of increased Bad phosphorylation and decreased caspase 3 activation [51]. Taken together, this combination of events appears to result in less apoptosis. In addition, these effects are associated with improved left ventricular function following cardioplegic arrest. However, this is not a universal finding in the literature. More work must be done to verify these conclusions and confirm if there truly is a definitive benefit to any one technique of hyperkalemic cardioplegia with respect to prevention of apoptosis.
2.4.3 Coronary vasomotor dysfunction
An extensive body of research has established that hyperkalemic solutions induce significant vasoconstriction when experimentally applied to coronary artery and aortic ring preparations [2]. Thus, it is no surprise that hyperkalemic cardioplegia induces significant functional changes to the microcirculation, especially the coronary circulation [52]. For example, a sizeable number of patients undergoing hyperkalemic cardioplegia experience coronary artery spasm [52].
Potassium can influence coronary vasoconstriction in several ways. Holding coronary vascular smooth muscle membrane potentials at sustained depolarization during hyperkalemic cardioplegia increases the likelihood of generating contractions [53]. Potassium may also act indirectly to cause vasospasm through action on the coronary endothelium. Indeed, endothelial vasoconstrictive and vasorelaxant factors govern homeostatic regulation of coronary vasomotor tone. These factors influence vascular smooth muscle through modulation of various cell membrane potassium channels, including calcium-activated potassium channels and ATP-activated potassium channels [54, 55]. Important endothelial-derived relaxing factors include nitric oxide, endothelial-derived hyperpolarizing factor (EDHF), and cyclooxygenase enzymes. Important endothelial-derived constricting factors include endothelin-1 and thromboxane A2.
Porcine models of hyperkalemic cardioplegia showed that hyperkalemia significantly attenuated EDHF-mediated relaxation in coronary artery preparations [56, 57]. Moreover, hyperkalemic vasoconstriction has also been linked with impaired nitric oxide release [58] and impaired acetylcholine-dependent vascular relaxation [59, 60]. Potential mechanisms at play may involve potassium-induced inhibition of G protein and non-G protein signal transduction pathways, increased reactive oxygen and nitrogen species generation, decreased activity of endothelial nitric oxide synthase, and increased arachidonic acid metabolism [2]. Curiously, hyperkalemic cardioplegia has also been associated with decreased responsiveness of human coronary arterioles to the endothelial vasoconstrictors endothelin-1 and thromboxane A2 [61, 62]. These findings testify to the complexity of mechanisms underpinning coronary vasomotor dysfunction following hyperkalemic cardioplegia, most of which remain to be elaborated.
2.4.4 Myocardial and coronary endothelial dysfunction
Despite its cardioprotective effects, hyperkalemic cardioplegia-reperfusion can exert detrimental effects on the myocardial and coronary endothelium, promoting endothelial dysfunction [63, 64]. One aspect of endothelial dysfunction—production of various endothelium-derived relaxing and contracting factors—was discussed earlier due to its relevance in coronary vasospasm. Other important features of endothelial dysfunction during hyperkalemic cardioplegic arrest include endothelial injury, inflammation, reactive oxygen species production, coagulation cascade dysfunction, and endothelial tight junction degradation [52, 65, 66, 67]. All these adverse effects may occur with potassium levels as low as 10 mM, well within the realm of most hyperkalemic cardioplegic solutions [2]. To elaborate, potassium concentrations of 30 mM in St. Thomas and Custodiol cardioplegic solutions proved considerably more damaging to the vascular endothelium than potassium concentrations of 20 mM, demonstrating the importance of strict potassium limits in hyperkalemic cardioplegic solutions [6].
A variety of structural changes to the vascular endothelium have been observed in experimental models of hyperkalemic cardioplegia. Key examples include endothelial intracellular vacuolization, membrane blebbing, adventitial fibrosis, and overall reduced viability [68, 69]. Furthermore, hyperkalemic cardioplegia promotes increased lipid uptake and cholesterol deposition in vascular intimae in primate models of post-graft venous atherosclerosis [70]. In addition, compromised endothelial adherens junctions during hyperkalemic cardioplegia mediate increased vascular permeability and tissue edema [67]. Indeed, animal models of cardioplegia/CPB show increased post-procedure VE cadherin, beta-catenin, and gamma-catenin fragments, all of which are important structural components of adherens junctions [71]. In humans, increased endothelial cadherin phosphorylation, and decreased overall beta-catenin levels, have been observed in atrial tissue following hyperkalemic cardioplegia/CPB [72].
Details of specific mechanisms underlying these endothelial disturbances remain largely unclear; however, many possibilities exist. For example, it is generally agreed that depolarization induced by hyperkalemic cardioplegia is a critical initiating step of the underlying pathophysiology [2]. Endothelial depolarization increases activation of neutrophils, inflammation, voltage sensitive NAPDH oxidases, and platelets [62, 63, 73, 74]. Inflammation and neutrophil activation often reinforce each other, as pro-inflammatory cytokines like IL-1, IL-6, and TNF-alpha further stimulate endothelial changes that promote neutrophil extravasation. NADPH oxidase catalyzes formation of important reactive oxygen species such as superoxide anions, which if left unchecked are severely cytotoxic. The amount of superoxide production during hyperkalemic cardioplegia has been linked to the extent of endothelial depolarization and translocation of the small G protein Rac from the cytosol to plasma membrane [75].
With respect to coagulation, potassium depolarization appears to have a direct stimulatory effect via enhancing ADP and collagen-induced platelet aggregation, along with an indirect effect through increased superoxide production [76, 77]. The latter appears to act through inhibition of endothelial NTPDases [78]. Membrane hyperpolarization reverses all these actions.
When left unchecked, sustained myocardial dysfunction following hyperkalemic cardioplegia-reperfusion may lead to myocardial stunning, a form of postoperative left ventricular dysfunction [1]. Myocardial stunning often manifests as markedly reduced cardiac output without obvious evidence of infarction or injury (e.g. no signs of elevated troponin or CKMB in blood). Like myocardial apoptosis, myocardial stunning represents another final common pathway of convergence for several different pathophysiological mechanisms of hyperkalemic cardioplegia, chiefly dysregulated free radical production, coagulation imbalances, and excessive catecholamine release [1]. However, unlike with apoptosis, in this scenario injury results from abnormal myocardial contractility as opposed to myocardial cell death.
2.5 Postoperative potassium abnormalities: physiology and management
Postoperative imbalances in a variety of different electrolytes, including calcium, magnesium, potassium, and phosphate, have been observed following cardioplegia/CPB. Here, we will focus on potassium, beginning with hypokalemia. Hypokalemia can be defined as a serum potassium level that is less than 3.5 mEq/L [78]. Postoperative hypokalemia is a common finding after cardiac surgery involving hyperkalemic cardioplegia and CPB, and manifests almost immediately after the patient is weaned off the bypass circuitry [79]. Hence IV potassium supplementation during cardioplegia is extremely important to mitigate against the most severe manifestations [80].
However, even with electrolyte supplementation in the operating room, CPB poses a high risk of post-procedure electrolyte depletion [81]. The pivotal role of potassium in normal cardiac contractility means that disturbances in potassium homeostasis significantly increase the risk of arrythmias and, in severe cases, sudden cardiac arrest. Indeed, arrythmias, especially atrial tachyarrhythmias (e.g. atrial fibrillation, atrial flutter) and, less frequently, ventricular arrhythmias, are a major source of morbidity and mortality following cardiac surgery [82, 83].
Specific mechanisms underpinning this phenomenon remain largely unclear; however, a variety of possibilities exist [78]. For example, poor oral intake of potassium-rich foods prior to cardiac surgery may contribute to enhanced depletion during surgery. In addition, prolonged preoperative use of digoxin, along with thiazide and loop diuretics may play a role. These agents may cause hypomagnesemia (low magnesium levels), which can contribute to extracellular potassium depletion. Under normal circumstances, intracellular magnesium binds to and blocks the pores of renal outer medullary potassium (ROMK) channels in the distal nephron, preventing outward flux of potassium into the renal tubular network [78]. Thus hypomagnesemia may remove this physiologic limiter, leading to increased renal clearance of potassium.
A hyperactive aldosterone response to stress may also be implicated, particularly in the context of congestive heart failure [78, 80]. Moreover, increased catecholamine (norepinephrine and epinephrine) release during cardiopulmonary bypass may facilitate hypokalemia given the influence of catecholamines on plasma potassium [84, 85]. Animal models have shown that elevated catecholamine levels can produce first, a transient hyperkalemia due to activation of hepatic calcium-dependent potassium channels by alpha adrenergic stimulation and second, a sustained hypokalemia by stimulation of skeletal muscle Na-K ATPase [86]. Such studies need to be replicated in humans undergoing cardiopulmonary bypass-hyperkalemic cardioplegia in order to verify the applicability of these putative mechanisms.
Because glucose is often given during cardioplegia, insulin may also be administered to minimize the chances of hyperglycemia. However, given that insulin acts as a regulator of potassium distribution between intracellular and extracellular fluid compartments by stimulating Na-K ATPase activity, it is possible that insulin administration during and after cardioplegia may contribute to potassium depletion [87]. Next, given that many cardioplegic solutions in current practice are cold hyperkalemic solutions, any potential impact of hypothermia on potassium homeostasis during cardiac surgery cannot be ignored. As with insulin, hypothermia has been linked to an intracellular shift of potassium away from the extracellular space through as-yet unelaborated mechanisms [88]. Finally, the CPB circuit itself has been shown to significantly dilute overall blood plasma protein concentrations, which may also affect plasma ion homeostasis [89].
In general, treatment of postoperative hypokalemia largely centers on administration of potassium chloride (KCl) solution to elevate extracellular potassium concentrations to physiologic levels. Indeed, in the case of pediatric cardiac ICU patients for whom enteral potassium supplementation is contraindicated, IV KCl administration is one of the only available tools for correcting hypokalemia [90]. For most patients, this proves sufficient to correct the imbalance and stave off the development of hypokalemia-induced arrhythmias. However, in a small minority, external KCl solution does not reverse the hypokalemia—and so in these patients, the chances of arrhythmias increase exponentially.
Although hypokalemia is the most common potassium electrolyte abnormality following hyperkalemic cardioplegia-CPB, postoperative hyperkalemia may occur under certain, albeit rarer, circumstances. In general, postoperative hyperkalemia is a concern mainly in patients with renal failure undergoing CPB, most likely due to renal tubular dysfunction [91]. Severe hyperkalemia may be treated with IV calcium gluconate, an insulin-dextrose regimen, and diuretics [92]. If a patient has end-stage renal disease, dialysis may be the best option to treat hyperkalemia, along with IV calcium to stabilize the myocardium and IV insulin to shift potassium into cells [93].
2.6 Alternatives to hyperkalemic cardioplegia
Hyperkalemic cardioplegia is by far the most widely used method of cardioplegia in current clinical practice. However, because of the numerous perioperative repercussions of hyperkalemic cardioplegia, a variety of attempts have been made to explore alternative approaches. Given that many adverse effects of hyperkalemic cardioplegia stem from its induction of depolarized arrest, one popular avenue of investigation has been the possibility of hyperpolarized arrest. Hyperpolarization is the natural resting state of cardiomyocytes, so in theory, arresting the heart at its baseline hyperpolarized state may better preserve physiological integrity. In isolated animal heart models, hyperpolarized arrest has been achieved via pharmacologic activation of ATP-sensitive potassium channels [94, 95]. Following reperfusion, this form of hyperpolarized arrest appeared to lead to improved postischemic functional recovery when compared to hearts protected with depolarized arrest.
Meanwhile, so-called “polarized arrest” has been proposed as another alternative to hyperkalemic cardioplegia. The core principle behind this concept is administration of sodium channel blockers, such as procaine in humans or tetrodotoxin in animal models [96]. Sodium channel blockade prevents depolarization-induced activation of calcium currents, which normally carry out the bulk of the cardiomyocyte action potential. Overall, in animal models, tetrodotoxin-induced polarized arrest reduces metabolic demands during ischemia, including myocardial oxygen consumption, more so than hyperkalemic cardioplegia [96]. Furthermore, polarized arrest may produce less significant postoperative ionic imbalances, with further protection provided by coincident administration of sodium/potassium/chloride transporter and sodium/proton exchanger inhibitors [96]. Nonetheless, more work needs to be done to verify the broader clinical applicability of these alternatives to hyperkalemic cardioplegia.
3. Conclusions
By taking advantage of the pivotal role of potassium in cardiomyocyte physiology, hyperkalemic cardioplegia has become an integral tool for cardiac surgery. From the early days of Dennis Melrose’s simple potassium citrate solution to complex modern-day formulations such as the Del Nido and Buckberg media, approaches to developing and administering hyperkalemic cardioplegic solutions have evolved considerably, with a continuing focus on developing the most cardioprotective and least damaging solutions possible. While initial approaches to hyperkalemic cardioplegia revolved around hypothermic solutions, normothermic/“warm” solutions, along with blood as opposed to crystalloid-based solutions, are gaining momentum as potential alternatives to mitigate adverse perioperative consequences of cold hyperkalemic cardioplegia. Some of those consequences include myocardial calcium loading, myocardial apoptosis, coronary vasomotor dysfunction, myocardial endothelial dysfunction, and myocardial stunning. With any form of hyperkalemic cardioplegia, plasma potassium abnormalities following reperfusion, mainly postoperative hypokalemia, remain a persistent clinical concern. And while most patients respond well to IV KCl supplementation, some do not and proceed to develop fatal arrythmias, underscoring the need for further research to understand the mechanisms at play and develop new treatments. In the future, it is possible that other approaches such as hyperpolarized or polarized arrest may challenge the widespread use of depolarized hyperkalemic cardioplegic arrest. Nevertheless, for the time being, hyperkalemic cardioplegia remains dominant in cardiac surgery, and will likely continue to be so for some time to come.
Acknowledgments
The authors have no acknowledgements.
Conflict of interest
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Notes/thanks/other declarations
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\n',keywords:"potassium, hypokalemia, hyperkalemia, low potassium, high potassium, hyperkalemic cardioplegia, cardiopulmonary bypass, cardiac surgery, open heart surgery, postoperative arrhythmias, perioperative arrhythmias",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78193.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78193.xml",downloadPdfUrl:"/chapter/pdf-download/78193",previewPdfUrl:"/chapter/pdf-preview/78193",totalDownloads:203,totalViews:0,totalCrossrefCites:1,dateSubmitted:"July 8th 2021",dateReviewed:"July 30th 2021",datePrePublished:"August 26th 2021",datePublished:null,dateFinished:"August 21st 2021",readingETA:"0",abstract:"Potassium homeostasis affects cardiac rhythm and contractility, along with vascular reactivity and vascular smooth muscle proliferation. This chapter will focus on potassium dynamics during and after cardiac surgery involving cardioplegic arrest and cardiopulmonary bypass (CPB). Hyperkalemic, hypothermic solutions are frequently used to induce cardioplegic arrest and protect the heart during cardiac surgery involving CPB. Common consequences of hyperkalemic cardioplegic arrest and reperfusion include microvascular dysfunction involving several organ systems and myocardial dysfunction. Immediately after CPB, blood potassium levels often drop precipitously due to a variety of factors, including CPB -induced electrolyte depletion and frequent, long-term administration of insulin during and after surgery. Meanwhile, some patients with pre-existing kidney dysfunction may experience postoperative hyperkalemia following cardioplegia. Any degree of postoperative hyper/hypokalemia significantly elevates the risk of cardiac arrythmias and subsequent myocardial failure. Therefore, proper management of blood potassium levels during and after cardioplegia/CPB is crucial for optimizing patient outcomes following cardiac surgery.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78193",risUrl:"/chapter/ris/78193",signatures:"Shawn Kant, Frank W. Sellke and Jun Feng",book:{id:"10794",type:"book",title:"Potassium in Human Health",subtitle:null,fullTitle:"Potassium in Human Health",slug:null,publishedDate:null,bookSignature:"Dr. Jie Tang",coverURL:"https://cdn.intechopen.com/books/images_new/10794.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-78985-732-0",printIsbn:"978-1-78985-731-3",pdfIsbn:"978-1-83880-835-8",isAvailableForWebshopOrdering:!0,editors:[{id:"181267",title:"Dr.",name:"Jie",middleName:null,surname:"Tang",slug:"jie-tang",fullName:"Jie Tang"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Potassium and cardiac surgery",level:"1"},{id:"sec_2_2",title:"2.1 Brief history of potassium cardioplegia",level:"2"},{id:"sec_3_2",title:"2.2 Types and techniques of potassium cardioplegia",level:"2"},{id:"sec_3_3",title:"Table 1.",level:"3"},{id:"sec_4_3",title:"2.2.2 Warm vs. cold",level:"3"},{id:"sec_5_3",title:"2.2.3 Anterograde vs. retrograde",level:"3"},{id:"sec_7_2",title:"2.3 Physiology of potassium cardioplegia during cardiac surgery",level:"2"},{id:"sec_7_3",title:"2.3.1 Physiology of cardiac muscle contraction",level:"3"},{id:"sec_8_3",title:"2.3.2 Physiology of potassium cardioplegia",level:"3"},{id:"sec_10_2",title:"2.4 Side effects of high potassium cardioplegia",level:"2"},{id:"sec_10_3",title:"2.4.1 Myocardial calcium loading",level:"3"},{id:"sec_11_3",title:"2.4.2 Myocardial apoptosis",level:"3"},{id:"sec_12_3",title:"2.4.3 Coronary vasomotor dysfunction",level:"3"},{id:"sec_13_3",title:"2.4.4 Myocardial and coronary endothelial dysfunction",level:"3"},{id:"sec_15_2",title:"2.5 Postoperative potassium abnormalities: physiology and management",level:"2"},{id:"sec_16_2",title:"2.6 Alternatives to hyperkalemic cardioplegia",level:"2"},{id:"sec_18",title:"3. Conclusions",level:"1"},{id:"sec_19",title:"Acknowledgments",level:"1"},{id:"sec_22",title:"Conflict of interest",level:"1"},{id:"sec_19",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Haddy, F. J., Vanhoutte, P. M., & Feletou, M. (2006). Role of potassium in regulating blood flow and blood pressure. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 290(3). https://doi.org/10.1152/ajpregu.00491.2005'},{id:"B2",body:'Dobson, G. P., Faggian, G., Onorati, F., & Vinten-Johansen, J. (2013). Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era? Frontiers in Physiology, 4. https://doi.org/10.3389/fphys.2013.00228'},{id:"B3",body:'Sarkar, M., & Prabhu, V. (2017). Basics of cardiopulmonary bypass. Indian Journal of Anaesthesia, 61(9), 760. https://doi.org/10.4103/ija.ija_379_17'},{id:"B4",body:'Maruyama, Y., Chambers, D. J., & Ochi, M. (2013). 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(1999). Polarization and myocardial protection. Current Opinion in Cardiology, 14(6), 495. https://doi.org/10.1097/00001573-199911000-00008'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Shawn Kant",address:null,affiliation:'
Division of Cardiothoracic Surgery, Department of Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA
'},{corresp:null,contributorFullName:"Frank W. Sellke",address:null,affiliation:'
Division of Cardiothoracic Surgery, Department of Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA
Division of Cardiothoracic Surgery, Department of Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA
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The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
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The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Permanent and unrestricted online access to your work
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
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Open Access Funding
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To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Choosing to publish with IntechOpen ensures the following benefits:
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+5,700 OA books published
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Lakka and Chandrasekar Kuppan",authors:[{id:"304950",title:"Prof.",name:"Chandrasekar",middleName:null,surname:"Kuppan",slug:"chandrasekar-kuppan",fullName:"Chandrasekar Kuppan"},{id:"309984",title:"Mr.",name:"Narasimha S",middleName:null,surname:"Lakka",slug:"narasimha-s-lakka",fullName:"Narasimha S Lakka"}]},{id:"33046",title:"Affinity Chromatography: Principles and Applications",slug:"affinity-chromatography-principles-and-applications",totalDownloads:48609,totalCrossrefCites:8,totalDimensionsCites:21,abstract:null,book:{id:"1490",slug:"affinity-chromatography",title:"Affinity Chromatography",fullTitle:"Affinity Chromatography"},signatures:"Sameh Magdeldin and Annette Moser",authors:[{id:"123648",title:"Dr.",name:"Sameh",middleName:null,surname:"Magdeldin",slug:"sameh-magdeldin",fullName:"Sameh Magdeldin"},{id:"136483",title:"Dr.",name:"Annette",middleName:"C.",surname:"Moser",slug:"annette-moser",fullName:"Annette Moser"}]},{id:"50574",title:"Bioinformatics for RNA‐Seq Data Analysis",slug:"bioinformatics-for-rna-seq-data-analysis",totalDownloads:5930,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"While RNA sequencing (RNA‐seq) has become increasingly popular for transcriptome profiling, the analysis of the massive amount of data generated by large‐scale RNA‐seq still remains a challenge. RNA‐seq data analyses typically consist of (1) accurate mapping of millions of short sequencing reads to a reference genome, including the identification of splicing events; (2) quantifying expression levels of genes, transcripts, and exons; (3) differential analysis of gene expression among different biological conditions; and (4) biological interpretation of differentially expressed genes. Despite the fact that multiple algorithms pertinent to basic analyses have been developed, there are still a variety of unresolved questions. In this chapter, we review the main tools and algorithms currently available for RNA‐seq data analyses, and our goal is to help RNA‐seq data analysts to make an informed choice of tools in practical RNA‐seq data analysis. In the meantime, RNA‐seq is evolving rapidly, and newer sequencing technologies are briefly introduced, including stranded RNA‐seq, targeted RNA‐seq, and single‐cell RNA‐seq.",book:{id:"5160",slug:"bioinformatics-updated-features-and-applications",title:"Bioinformatics",fullTitle:"Bioinformatics - Updated Features and Applications"},signatures:"Shanrong Zhao, Baohong Zhang, Ying Zhang, William Gordon,\nSarah Du, Theresa Paradis, Michael Vincent and David von Schack",authors:[{id:"176364",title:"Dr.",name:"Shanrong",middleName:null,surname:"Zhao",slug:"shanrong-zhao",fullName:"Shanrong Zhao"}]},{id:"49873",title:"An Introduction to Actinobacteria",slug:"an-introduction-to-actinobacteria",totalDownloads:8089,totalCrossrefCites:29,totalDimensionsCites:101,abstract:"Actinobacteria, which share the characteristics of both bacteria and fungi, are widely distributed in both terrestrial and aquatic ecosystems, mainly in soil, where they play an essential role in recycling refractory biomaterials by decomposing complex mixtures of polymers in dead plants and animals and fungal materials. They are considered as the biotechnologically valuable bacteria that are exploited for its secondary metabolite production. Approximately, 10,000 bioactive metabolites are produced by Actinobacteria, which is 45% of all bioactive microbial metabolites discovered. Especially Streptomyces species produce industrially important microorganisms as they are a rich source of several useful bioactive natural products with potential applications. Though it has various applications, some Actinobacteria have its own negative effect against plants, animals, and humans. On this context, this chapter summarizes the general characteristics of Actinobacteria, its habitat, systematic classification, various biotechnological applications, and negative impact on plants and animals.",book:{id:"5056",slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Ranjani Anandan, Dhanasekaran Dharumadurai and Gopinath\nPonnusamy Manogaran",authors:[{id:"48914",title:"Dr.",name:"Dharumadurai",middleName:null,surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}]},{id:"72074",title:"The Chemistry Behind Plant DNA Isolation Protocols",slug:"the-chemistry-behind-plant-dna-isolation-protocols",totalDownloads:3691,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Various plant species are biochemically heterogeneous in nature, a single deoxyribose nucleic acid (DNA) isolation protocol may not be suitable. There have been continuous modification and standardization in DNA isolation protocols. Most of the plant DNA isolation protocols used today are modified versions of hexadecyltrimethyl-ammonium bromide (CTAB) extraction procedure. Modification is usually performed in the concentration of chemicals used during the extraction procedure according to the plant species and plant part used. Thus, understanding the role of each chemical (viz. CTAB, NaCl, PVP, ethanol, and isopropanol) used during the DNA extraction procedure will benefit to set or modify protocols for more precisions. A review of the chemicals used in the CTAB method of DNA extraction and their probable functions on the highly evolved yet complex to students and researchers has been summarized.",book:{id:"8912",slug:"biochemical-analysis-tools-methods-for-bio-molecules-studies",title:"Biochemical Analysis Tools",fullTitle:"Biochemical Analysis Tools - Methods for Bio-Molecules Studies"},signatures:"Jina Heikrujam, Rajkumar Kishor and Pranab Behari Mazumder",authors:[{id:"74521",title:"Dr.",name:"Rajkumar",middleName:null,surname:"Kishor",slug:"rajkumar-kishor",fullName:"Rajkumar Kishor"},{id:"309357",title:"Prof.",name:"Pranab Behari",middleName:null,surname:"Mazumder",slug:"pranab-behari-mazumder",fullName:"Pranab Behari Mazumder"},{id:"318351",title:"Ph.D. Student",name:"Jina",middleName:null,surname:"Heikrujam",slug:"jina-heikrujam",fullName:"Jina Heikrujam"}]}],onlineFirstChaptersFilter:{topicId:"6",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82531",title:"Abnormal Iron Metabolism and Its Effect on Dentistry",slug:"abnormal-iron-metabolism-and-its-effect-on-dentistry",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.104502",abstract:"Iron is a necessary micro-nutrient for proper functioning of the erythropoietic, oxidative and cellular metabolism. The iron balance in the body adversely affects the normal physiologic functioning of the body and structures in the oral cavity. Various abnormalities develop owing to improper iron metabolism in the body which reflects in the oral cavity. The toxicity of iron has to be well understood to immediately identify the hazardous effects which arise owing to it and to manage it. It has been very well mentioned in the chapter. The manifestations of defects of iron metabolism in the oral cavity should be carefully studied to improve the prognosis of the treatment of the same. Disorders related to iron metabolism should be managed for improvement in the quality of life of the patient.",book:{id:"10842",title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg"},signatures:"Chinmayee Dahihandekar and Sweta Kale Pisulkar"},{id:"82291",title:"The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration",slug:"the-role-of-oxidative-stress-in-the-onset-and-development-of-age-related-macular-degeneration",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.105599",abstract:"Age-related macular degeneration (AMD) is a complex, degenerative and progressive chronic disease that leads to severe visual loss. The prevalence of early AMD accounts for 18% in the population between 65 and 74 years of age and even 30% in subjects older than 74 years. The articles published in the last decade point out to a significant role of oxidative stress in the onset and development of age-related macular degeneration. Generally, reactive oxygen species (ROS) are produced in the eye during light absorption and physiological metabolic processes. The level of oxidative stress is kept under control by the action of antioxidants and reparative enzymes. Excessive synthesis of ROS leads to increased oxidative modification of lipids, proteins and DNA, causing oxidative damage of cytoplasmic and nuclear cell elements and changes of the extracellular matrix. The accumulation of oxidatively modified compounds in drusen deposits will initiate the onset and development of AMD. The objective of this review was to highlight the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.",book:{id:"11671",title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg"},signatures:"Emina Čolak, Lepša Žorić, Miloš Mirković, Jana Mirković, Ilija Dragojević, Dijana Mirić, Bojana Kisić and Ljubinka Nikolić"},{id:"82517",title:"MicroRNAs and Pancreatic ß Cell Functional Modulation",slug:"micrornas-and-pancreatic-cell-functional-modulation",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105588",abstract:"Recent reports of diabetes susceptibility loci located on the non-coding regions of the genome highlight the importance of epigenetic control in health and disease. Specifically, microRNAs have shown to have an important regulatory role in pancreatic ß cell physiology. Human studies implicated that ß cell mass and function are regulated by microRNAs in health and disease. Further, the microRNAs are also implicated in ensuing diabetic complications. Delineating the peculiar role of microRNAs in ß cell physiology and pathophysiology will fill the missing gaps in our current knowledge and help to devise better treatment regimens for diabetes. This chapter will discuss multiple effects of different microRNAs on the ß cell physiology in the context of maintenance and function in Type 2 diabetes mellitus.",book:{id:"11353",title:"Recent Advances in Non-Coding RNAs",coverURL:"https://cdn.intechopen.com/books/images_new/11353.jpg"},signatures:"Shahzad Irfan, Farhat Jabeen and Haseeb Anwar"},{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105450",abstract:"Endoplasmic Reticulum (ER) is the largest and one of the most complex cellular structures, indicating its widespread importance and variety of functions, including synthesis of membrane and secreted proteins, protein folding, calcium storage, and membrane lipid biogenesis. Moreover, the ER is implicated in cholesterol, plasmalogen, phospholipid, and sphingomyelin biosynthesis. Furthermore, the ER is in contact with most cellular organelles, such as mitochondria, peroxisomes, Golgi apparatus, lipid droplets, plasma membrane, etc. Peroxisomes are synthesized from a specific ER section, and they are related to very-long-chain fatty acid metabolism. Similarly, lipid droplets are vital structures in lipid homeostasis that are formed from the ER membrane. Additionally, there is a specific region between the ER-mitochondria interface called Mitochondria-Associated Membranes (MAMs). This small cytosolic gap plays a key role in several crucial mechanisms from autophagosome synthesis to phospholipid transfer. Due to the importance of the ER in a variety of biological processes, alterations in its functionality have relevant implications for multiple diseases. Nowadays, a plethora of pathologies like non-alcoholic steatohepatitis (NASH), cancer, and neurological alterations have been associated with ER malfunctions.",book:{id:"11674",title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg"},signatures:"Raúl Ventura and María Isabel Hernández-Alvarez"},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105008",abstract:"SARS-CoV-2 virus infection causes the Covid-19 disease pandemic. Purinergic signaling is a form of extracellular signaling. Purinergic signaling plays significant role in the pathology of Covid-19. Purinergic system includes extracellular nucleotides, nucleosides, ectonucleotidases, and purinergic receptors. ATP, ADP, and adenosine are the main nucleotides, nucleosides. CD39 and CD73 are the main ectonucleotidases. There are two classes of purinergic receptors, P1 and P2. Each of them can be further divided, P1 into A1, A2A, A2B, and A3, P2 into P2X, and P2Y. In Covid-19, the purinergic system is disordered. SARS-CoV-2 viruses invading leads to extracellular ATP and ADP accumulation, purinergic receptor abnormally activation, tissue homeostasis balance is broken, which lead to inflammation even hyperinflammation with cytokine storm and thrombosis et al. symptoms. Currently, Covid-19 therapeutic medicine is still in shortage. Target purinergic system components is a promising way to treat Covid-19, which will help inhibit inflammation and prevent thrombosis. Currently, many relevant preclinical and clinical trials are ongoing. Some are very promising.",book:{id:"10801",title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg"},signatures:"Hailian Shen"},{id:"81708",title:"High Throughput Methods to Transfer DNA in Cells and Perspectives",slug:"high-throughput-methods-to-transfer-dna-in-cells-and-perspectives",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.104542",abstract:"Genome sequencing led to thousands of genes to study and their molecular cloning to provide ORF collection plasmids. The main approach to study their function involves analysis of the biological consequences of their expression or knockdown, in a cellular context. Given that, the starting point of such experiments is the delivery of the exogenous material, including plasmid DNA in cells. During the last decades, efforts were made to develop efficient methods and protocols to achieve this goal. The present chapter will first give a rapid overview of the main DNA transfer methods described so far: physical, chemical, and biological. Secondly, it will focus on the different methods having reached high-throughput nowadays. Finally, it will discuss the perspectives of this field in terms of future enhancements.",book:{id:"11356",title:"Molecular Cloning",coverURL:"https://cdn.intechopen.com/books/images_new/11356.jpg"},signatures:"Colin Béatrice and Couturier Cyril"}],onlineFirstChaptersTotal:62},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:16,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. In 2017, Usha was awarded the Marquis Who’s Who Lifetime Achiever Award.",institutionString:null,institution:{name:"RMIT University",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"91",title:"Sustainable Economy and Fair Society",coverUrl:"https://cdn.intechopen.com/series_topics/covers/91.jpg",isOpenForSubmission:!0,editor:{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo",profilePictureURL:"https://mts.intechopen.com/storage/users/181603/images/system/181603.jpg",biography:"Antonella Petrillo is a Professor at the Department of Engineering of the University of Naples “Parthenope”, Italy. She received her Ph.D. in Mechanical Engineering from the University of Cassino. Her research interests include multi-criteria decision analysis, industrial plant, logistics, manufacturing and safety. She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. She has over 160 Scientific Publications in International Journals and Conferences and she is the author of 5 books on Innovation and Decision Making in Industrial Applications and Engineering.",institutionString:null,institution:{name:"Parthenope University of Naples",institutionURL:null,country:{name:"Italy"}}},editorTwo:null,editorThree:null},{id:"92",title:"Health and Wellbeing",coverUrl:"https://cdn.intechopen.com/series_topics/covers/92.jpg",isOpenForSubmission:!0,editor:{id:"348225",title:"Prof.",name:"Ann",middleName:null,surname:"Hemingway",slug:"ann-hemingway",fullName:"Ann Hemingway",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035LZFoQAO/Profile_Picture_2022-04-11T14:55:40.jpg",biography:"Professor Hemingway is a public health researcher, Bournemouth University, undertaking international and UK research focused on reducing inequalities in health outcomes for marginalised and excluded populations and more recently focused on equine assisted interventions.",institutionString:null,institution:{name:"Bournemouth University",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"93",title:"Inclusivity and Social Equity",coverUrl:"https://cdn.intechopen.com/series_topics/covers/93.jpg",isOpenForSubmission:!0,editor:{id:"210060",title:"Prof. Dr.",name:"Ebba",middleName:null,surname:"Ossiannilsson",slug:"ebba-ossiannilsson",fullName:"Ebba Ossiannilsson",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6LkBQAU/Profile_Picture_2022-02-28T13:31:48.png",biography:"Professor Dr. Ebba Ossiannilsson is an independent researcher, expert, consultant, quality auditor and influencer in the fields of open, flexible online and distance learning (OFDL) and the 'new normal'. Her focus is on quality, innovation, leadership, and personalised learning. She works primarily at the strategic and policy levels, both nationally and internationally, and with key international organisations. She is committed to promoting and improving OFDL in the context of SDG4 and the future of education. Ossiannilsson has more than 20 years of experience in her current field, but more than 40 years in the education sector. She works as a reviewer and expert for the European Commission and collaborates with the Joint Research Centre for Quality in Open Education. Ossiannilsson also collaborates with ITCILO and ICoBC (International Council on Badges and Credentials). She is a member of the ICDE Board of Directors and has previously served on the boards of EDEN and EUCEN. Ossiannilsson is a quality expert and reviewer for ICDE, EDEN and the EADTU. She chairs the ICDE OER Advocacy Committee and is a member of the ICDE Quality Network. She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. 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In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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