\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\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:"10548",leadTitle:null,fullTitle:"Lean Manufacturing",title:"Lean Manufacturing",subtitle:null,reviewType:"peer-reviewed",abstract:"Lean manufacturing is a process used in production to maximize efficiency and minimize waste by considering sustainability and the environment. This book presents a comprehensive overview of lean manufacturing in various enterprises, including manufacturing, construction, and the fabric and textile industry, among others. Chapters cover such topics as barriers to lean manufacturing, enterprise modeling, lean practices and circular economies, and more.",isbn:"978-1-83969-150-8",printIsbn:"978-1-83969-149-2",pdfIsbn:"978-1-83969-151-5",doi:"10.5772/intechopen.92922",price:119,priceEur:129,priceUsd:155,slug:"lean-manufacturing",numberOfPages:244,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7409b2acd5150a93004300800918b736",bookSignature:"Karmen Pažek",publishedDate:"November 3rd 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10548.jpg",numberOfDownloads:3491,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 20th 2020",dateEndSecondStepPublish:"November 17th 2020",dateEndThirdStepPublish:"January 16th 2021",dateEndFourthStepPublish:"April 6th 2021",dateEndFifthStepPublish:"June 5th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"179642",title:"Prof.",name:"Karmen",middleName:null,surname:"Pažek",slug:"karmen-pazek",fullName:"Karmen Pažek",profilePictureURL:"https://mts.intechopen.com/storage/users/179642/images/system/179642.jpg",biography:"Karmen Pažek was born in 1976. She graduated from the Faculty of Agriculture, University of Maribor, Slovenia, in 2000. In 2001 she was employed at the same faculty as an assistant for the field of grassland management. Between 2000 and 2003, she enrolled in the master\\'s study program in Agriculture Economics at the same faculty, and in 2003 she received her master\\'s degree. In the same year, she enrolled in a doctoral study in Agriculture Economics at the Faculty of Agriculture and obtained the status of a research assistant. In 2006 she successfully completed her Ph.D. in Agriculture Economics.\n\n\n\nSince 2006 she has been habilitated at the University of Maribor, and Life Sciences (she has been a full professor since 2016) for the field of Farm management. She holds several courses at all levels of study. She is currently the head of the 1st-degree study Agriculture Economics and Rural Development and the Vice Dean for Education.\n\n\n\nHer research includes the development of decision support tools and systems for farm management (simulation modeling, multicriteria decision analysis, option models, risk management), the economics of agricultural production, and other modern methods of operational research.",institutionString:"University of Maribor",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Maribor",institutionURL:null,country:{name:"Slovenia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1360",title:"Production Engineering",slug:"technology-industrial-engineering-production-engineering"}],chapters:[{id:"76130",title:"Application of Lean in a Small and Medium Enterprise",doi:"10.5772/intechopen.97059",slug:"application-of-lean-in-a-small-and-medium-enterprise",totalDownloads:199,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Application of lean principles in manufacturing as well as services has been revolutionizing the operations for more than five decades. Many large as well as small enterprises have implemented lean and reported benefits in both direct and indirect activities of business. Due to advent of digital technologies and better understanding of process improvement approaches made lean much more effective across many sectors. In this chapter, we highlight various elements of lean and its application to a small enterprise in food processing sector in India. We draw some useful insights based on the implementation of lean and challenges faced by SMEs.",signatures:"Venkataramanaiah Saddikuti, Saketh Saddikuti Venkat and Ganesh Babu Shanmugam",downloadPdfUrl:"/chapter/pdf-download/76130",previewPdfUrl:"/chapter/pdf-preview/76130",authors:[{id:"292211",title:"Associate Prof.",name:"Venkataramanaiah",surname:"Saddikuti",slug:"venkataramanaiah-saddikuti",fullName:"Venkataramanaiah Saddikuti"},{id:"337430",title:"Mr.",name:"Saketh",surname:"Saddikuti Venkat",slug:"saketh-saddikuti-venkat",fullName:"Saketh Saddikuti Venkat"},{id:"349737",title:"Mr.",name:"Ganesh Babu",surname:"Shanmugam",slug:"ganesh-babu-shanmugam",fullName:"Ganesh Babu Shanmugam"}],corrections:null},{id:"75200",title:"Lean and Kaizen: The Past and the Future of the Methodologies",doi:"10.5772/intechopen.96169",slug:"lean-and-kaizen-the-past-and-the-future-of-the-methodologies",totalDownloads:360,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Lean and Kaizen improvement methodologies have been in the entrepreneurship spotlight for a long time. They can be adopted by any kind of enterprise, and they succeed in producing better long-term results, improving their performance, but most important, influencing the philosophy of the organizations implemented. In this research, many case studies and success stories of companies implementing Kaizen or/and Lean methodologies, or even the new Lean Kaizen methodology, will be introduced. We attempt to evaluate the performance of Lean and Kaizen implemented companies and distinguish the elements that made the difference. Maybe, it is some specific tool, or an aspect in the culture that was enhanced, since the implementation of these business process improvement methodologies. Finally, thoughts and estimations will be presented, regarding the future of these methodologies, in the unstable and rapidly changing economic environment.",signatures:"Vasileios Ismyrlis",downloadPdfUrl:"/chapter/pdf-download/75200",previewPdfUrl:"/chapter/pdf-preview/75200",authors:[{id:"190036",title:"Dr.",name:"Vasileios",surname:"Ismyrlis",slug:"vasileios-ismyrlis",fullName:"Vasileios Ismyrlis"}],corrections:null},{id:"76432",title:"Introduction to Lean Waste and Lean Tools",doi:"10.5772/intechopen.97573",slug:"introduction-to-lean-waste-and-lean-tools",totalDownloads:277,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the turbulent and complex business environments, many Indian SMEs are facing stiff competition in the domestic as well as in the global market from their multinational counterpart. The concept of lean has gained prominence due to the fact that the resource based competitive advantages are no longer sufficient in this economy. Hence, lean is no longer merely an option but rather a core necessity for engineering industries situated in any part of the globe, if they have to compete successfully. Lean Manufacturing (LM) which provides new opportunities to create and retain greater value from the employee of the industry based on their core business competencies. The challenge of capturing, organizing, and disseminating throughout the aggregate business unit is a huge responsibility of the top management. The success of any industry depends on how well it can manage its resources and translate in to action. The adoption of lean manufacturing through effective lean practices depends on interpretations of past experiences and present information resides in the industry. Generally, in an industry, some tangible and intangible factors exist in the form of non-value adding activities which hinder the smooth lean implementation are known as lean manufacturing barriers (LMBs).",signatures:"Shyam Sunder Sharma and Rahul Khatri",downloadPdfUrl:"/chapter/pdf-download/76432",previewPdfUrl:"/chapter/pdf-preview/76432",authors:[{id:"311981",title:"Dr.",name:"Shyam Sunder",surname:"Sharma",slug:"shyam-sunder-sharma",fullName:"Shyam Sunder Sharma"},{id:"338090",title:"Mr.",name:"Rahul",surname:"Khatri",slug:"rahul-khatri",fullName:"Rahul Khatri"}],corrections:null},{id:"76093",title:"Effect of Lean Practices on Organizational Performance",doi:"10.5772/intechopen.96482",slug:"effect-of-lean-practices-on-organizational-performance",totalDownloads:129,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The study focuses on the analysis of the direct effect of Lean Manufacturing (LM) practices on operational performance in manufacturing industry. A model for evaluating the effect of LM is developed taking into consideration as a fundamental variable that affects the causal relationship between LM practices and operational performance. A structural equation model was proposed and investigated across the manufacturing industry in India. A structured survey questionnaire was used to collect empirical data from 400 Indian companies. A total of 203 usable responses were obtained giving a response rate of 53%. The data was analyzed using SPSS- AMOS software. The results revealed that LM practices directly and positively affected operational performance. The results indicated that the structural equation model remained invariant across the Industry. The study provides further evidence to managers and practitioner on the effect of LM practices on operational performance in developing countries like India.",signatures:"Lokpriya Mohanrao Gaikwad and Vivek K. Sunnapwar",downloadPdfUrl:"/chapter/pdf-download/76093",previewPdfUrl:"/chapter/pdf-preview/76093",authors:[{id:"246830",title:"Prof.",name:"Lokpriya Mohanrao",surname:"Gaikwad",slug:"lokpriya-mohanrao-gaikwad",fullName:"Lokpriya Mohanrao Gaikwad"},{id:"251857",title:"Dr.",name:"Vivek K.",surname:"Sunnapwar",slug:"vivek-k.-sunnapwar",fullName:"Vivek K. Sunnapwar"}],corrections:null},{id:"75353",title:"Enhancement of Textile Supply Chain Performance through Optimal Capacity Planning",doi:"10.5772/intechopen.96292",slug:"enhancement-of-textile-supply-chain-performance-through-optimal-capacity-planning",totalDownloads:233,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Manufacturing companies in the textile and apparel field face stiff competition due to the globalization of trade between suppliers, producers and customers. To meet this challenge, they need to be efficient by adopting new lean manufacturing approaches and new analysis and management tools leading to more flexible and agile production and distribution processes. For the textile and apparel industry, where products’ life cycle is short due to fashion changes, a new integrated approach of production and distribution planning is needed. Based on linear programming techniques and integrating subcontracting activities, our approach takes into account the characteristics of demand, including its short life cycle, seasonality and fashion effect. For these reasons, a sequential approach is adopted, combining tactical and operational decision levels for production and distribution activities, in order to satisfy customer needs at lower cost by reacting quickly to changes and delivering on time. The deployed approach is structured according to the DMAIC lean tool. Validated on real instances, this approach proves its efficiency by achieving cost reduction when internal production capacity is adequately and efficiently planned.",signatures:"Imen Safra and Kaouther Ghachem",downloadPdfUrl:"/chapter/pdf-download/75353",previewPdfUrl:"/chapter/pdf-preview/75353",authors:[{id:"336845",title:"Assistant Prof.",name:"safra",surname:"Imen",slug:"safra-imen",fullName:"safra Imen"},{id:"345868",title:"Dr.",name:"Kaouther",surname:"Ghachem",slug:"kaouther-ghachem",fullName:"Kaouther Ghachem"}],corrections:null},{id:"75657",title:"From Lean Manufacturing to Lean Construction: How Principles, Tools, and Techniques Evolved",doi:"10.5772/intechopen.96191",slug:"from-lean-manufacturing-to-lean-construction-how-principles-tools-and-techniques-evolved",totalDownloads:309,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Lean manufacturing first emerged in the automotive industry. However, low productivity and low efficiency in production are major problems for the majority of industries relying on a heavy workforce. Being one of these, the construction industry suffers from low productivity rates along with inefficient work practices. To prevent those, the industry has shifted its focus from the traditional approach to a more innovative one, which is called Lean construction. Lean construction aims to maximize value while minimizing waste. Therefore, it intends to create safer, smoother, and more efficient processes to eliminate waste. This chapter focuses on Lean construction and highlights the generic Lean tools and techniques practiced in the construction industry indicating its historical journey from Lean manufacturing. The chapter aims to raise awareness towards the efficiency of Lean methods in the construction industry with respect to practices observed in manufacturing.",signatures:"Sevilay Demirkesen",downloadPdfUrl:"/chapter/pdf-download/75657",previewPdfUrl:"/chapter/pdf-preview/75657",authors:[{id:"338001",title:"Assistant Prof.",name:"Sevilay",surname:"Demirkesen",slug:"sevilay-demirkesen",fullName:"Sevilay Demirkesen"}],corrections:null},{id:"75939",title:"Model-Based Enterprise Continuous Improvement",doi:"10.5772/intechopen.96856",slug:"model-based-enterprise-continuous-improvement",totalDownloads:224,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The enterprise reengineering based on enterprise modelling is usually carried out within the framework of conventional projects. This leads to relatively long projects that are not compatible with a highly variable economic environment. The objective of the evolution management presented here is to use enterprise modelling and all the benefits it brings in a framework that allows for more continuous improvement than is generally observed. The proposed architecture is made up of three levels: a strategic level based on performance measurement, a tactical level that manages system migration and is based on enterprise models, and an operational level consisting of managing a portfolio of evolution projects. Together, these allow a shorter set of projects to be carried out, while remaining coherent and aligned with the company’s strategy. This approach puts enterprise modelling methods and continuous improvement/Lean management approaches into perspective, allowing complementarities and opening up interesting perspectives concerning enterprise re-engineering methods.",signatures:"Bruno Vallespir and Anne Zouggar-Amrani",downloadPdfUrl:"/chapter/pdf-download/75939",previewPdfUrl:"/chapter/pdf-preview/75939",authors:[{id:"345188",title:"Prof.",name:"Bruno",surname:"Vallespir",slug:"bruno-vallespir",fullName:"Bruno Vallespir"},{id:"348617",title:"Dr.",name:"Anne",surname:"Zougar-Amrani",slug:"anne-zougar-amrani",fullName:"Anne Zougar-Amrani"}],corrections:null},{id:"75617",title:"Single Minute Exchange of Dies: Classical Tool of Lean Manufacturing",doi:"10.5772/intechopen.96665",slug:"single-minute-exchange-of-dies-classical-tool-of-lean-manufacturing",totalDownloads:251,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Effective utilization of the resources is the need of an hour particularly when it comes to the manufacturing industry. It is having a paramount importance to have a proper utilization of the resources, on the same line in any manufacturing industries to reduce the setup time is also one of the ways to do so. Single Minute Exchange of Dies (SMED) is one of the classical method which is normally used to reduce the setup time. In this technique complete videography of the existing changeover is done and then by analyzing it waste activities identified and other improvement plant has been done in each iteration. The chapter also showcases the SMED technique applications in a gear industry. Remarkable resources and results have been achieved through the implementation of classical tool of Lean manufacturing is made.",signatures:"Yash Dave",downloadPdfUrl:"/chapter/pdf-download/75617",previewPdfUrl:"/chapter/pdf-preview/75617",authors:[{id:"338618",title:"Dr.",name:"Yash",surname:"Dave",slug:"yash-dave",fullName:"Yash Dave"}],corrections:null},{id:"75408",title:"Lean Manufacturing as a Strategy for Continuous Improvement in Organizations",doi:"10.5772/intechopen.96427",slug:"lean-manufacturing-as-a-strategy-for-continuous-improvement-in-organizations",totalDownloads:324,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The implementation of lean manufacturing is one of the most discussed and studied topics in management; references are at the business, educational and public levels. However, the changes faced in the fourth industrial revolution generate challenges that will only encounter solution through innovative efforts and industrial improvements as well as a radical change in our way of interacting. In the current revolution, there are digital changes that cause ruptures in social, economic and political aspects, and the administrative process is part of it, this chapter proposes to analyze the implementation of lean manufacturing in the process of continuous improvement in business organizations through a literary review of the implementation of tools.",signatures:"María Marcela Solís-Quinteros, Carolina Zayas-Márquez, Luis Alfredo Ávila-López and Teresa Carrillo-Gutirrez",downloadPdfUrl:"/chapter/pdf-download/75408",previewPdfUrl:"/chapter/pdf-preview/75408",authors:[{id:"281004",title:"Dr.",name:"María Marcela",surname:"Solís-Quinteros",slug:"maria-marcela-solis-quinteros",fullName:"María Marcela Solís-Quinteros"},{id:"343581",title:"Dr.",name:"Luis Alfredo",surname:"Avila-Lopez",slug:"luis-alfredo-avila-lopez",fullName:"Luis Alfredo Avila-Lopez"},{id:"343697",title:"Dr.",name:"Carolina",surname:"Zayas-Márquez",slug:"carolina-zayas-marquez",fullName:"Carolina Zayas-Márquez"},{id:"343698",title:"Dr.",name:"Teresa",surname:"Carrillo-Gutiérrez",slug:"teresa-carrillo-gutierrez",fullName:"Teresa Carrillo-Gutiérrez"}],corrections:null},{id:"74769",title:"Development of Integrated Lean Six Sigma-Baldrige Framework for Manufacturing Waste Minimization: A Case of NAS Foods Plc",doi:"10.5772/intechopen.95279",slug:"development-of-integrated-lean-six-sigma-baldrige-framework-for-manufacturing-waste-minimization-a-c",totalDownloads:329,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The aim of this study objective is to develop an integrated constant quality improvement model so as to minimize unwanted biscuit processing industry wastes. The method used was lean- six- sigma elements to define measure and improve unwanted process company wastes. In other word, Baldrige with six-sigma were created to define, measure and improve management perspectives. The tasks were integrated using both quantitative and qualitative analyzing tools implementing mixed strategies. The result was improved by using FMEA analysis was carried out at each stage of the existing process used to determine the failure of the process and to analyses and improve the production quality. The SPSS software was also used. In the finding section, the correlation and regression analysis has shown that there is strong relationship between each variance. There are different wastes that identified in six sigma (DMAIC) on NAS food Plc as a result; the value of waste ratio indicated is 36.7%. This show non-lean of the food industry is practiced. The defect of the company also calculated and defect per million are 67,308. This shows that the biscuit production has a production capability with a failure of 67,308 every 1000,000 productions it high failure rate. The contribution of the paper has indicated that there are limited studies were conducted so far to implement waste minimization tools like six-sigma, lean and MBNQA framework approach integration for food processing industry.",signatures:"Kassu Jilcha Sileyew and Selamawit Gebreyohanis",downloadPdfUrl:"/chapter/pdf-download/74769",previewPdfUrl:"/chapter/pdf-preview/74769",authors:[{id:"292841",title:"Ph.D.",name:"Kassu",surname:"Jilcha Sileyew",slug:"kassu-jilcha-sileyew",fullName:"Kassu Jilcha Sileyew"},{id:"338417",title:"Ms.",name:"Selamawit",surname:"Gebreyohanis",slug:"selamawit-gebreyohanis",fullName:"Selamawit Gebreyohanis"}],corrections:null},{id:"75149",title:"Analysis, an Anathema: Is That a Fervent Diatribe of Lean?",doi:"10.5772/intechopen.96166",slug:"analysis-an-anathema-is-that-a-fervent-diatribe-of-lean-",totalDownloads:221,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Should there be an understanding that rigor in analysis must be out-of-bounds for Lean initiatives? Will this rigor not facilitate a benchmarking of Lean initiatives? Why not a Lean initiative cause-consequence assessment not performed for building future fault tolerance? The effectiveness of a company’s strategy is critical to its success or failure. Lean strategy seems to be claimed as a widely recognized factor for business success and competitive advantage. However, empirical evidences do not promote the idea that Lean has delivered results every time. Study results indicate that success or failure of lean initiatives strongly depends on how companies approach it and on whether company has created their own curated philosophy towards Lean. Then, success is not dependent alone on a strategy, but on how daily operations are aligned to strategy. This chapter aims to address the above questions and a greater number of questions that we experience on a day-to-day basis with regard to Lean applications in the real world. Chapter Learning Objectives: Understanding Lean, Lean failure modes, and Lean initiative precautions.",signatures:"Sajit Jacob and Krishnamurthy Kothandaraman",downloadPdfUrl:"/chapter/pdf-download/75149",previewPdfUrl:"/chapter/pdf-preview/75149",authors:[{id:"299036",title:"Mr.",name:"Sajit",surname:"Jacob",slug:"sajit-jacob",fullName:"Sajit Jacob"},{id:"299213",title:"Dr.",name:"Krishnamurthy",surname:"Kothandaraman",slug:"krishnamurthy-kothandaraman",fullName:"Krishnamurthy Kothandaraman"}],corrections:null},{id:"76883",title:"Lean Manufacturing towards Green Manufacturing Practices and Its Implementation in SME’s",doi:"10.5772/intechopen.97389",slug:"lean-manufacturing-towards-green-manufacturing-practices-and-its-implementation-in-sme-s",totalDownloads:171,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The manufacturing SMEs are facing the burden of non-equilibrium of the supply–demand chain along with the global change in the climate. Several SMEs are looking for a substitute that can create a balance between performance and the environment. In spite of numerous studies related to green and lean that has been evolved, none of them is able to clearly define the spheres of green and lean. Here in this chapter, there is an exploration of advancement of lean and green manufacturing and its impact on other sectors. It also highlights the methodology adopted in implementing the same. This chapter recognizes the commonalities between lean and green approaches, the collaboration and impact, techniques involved. Also, the impediments and perplexities confronted by the manufacturing sector are examined. Further, this gives a better understanding of the challenges before implementing lean with green. This chapter also recognizes possible gaps in the literature that will help to eliminate the barrier toward this Neo manufacturing.",signatures:"J.P. Rishi",downloadPdfUrl:"/chapter/pdf-download/76883",previewPdfUrl:"/chapter/pdf-preview/76883",authors:[{id:"339553",title:"Dr.",name:"J.P.",surname:"Rishi",slug:"j.p.-rishi",fullName:"J.P. Rishi"}],corrections:null},{id:"75839",title:"Lean Manufacturing Practices and Environmental Performance",doi:"10.5772/intechopen.96973",slug:"lean-manufacturing-practices-and-environmental-performance",totalDownloads:300,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Lean manufacturing is considered a rewarding production strategy due to its positive effects on organizational and economic efficiency in various industries. Given the growing ecological consciousness, environmental achievements of lean manufacturing also incorporate a strong economic relevance. The main objective of this chapter is, therefore, to investigate the impact of lean manufacturing practices on environmental performance and the existing coherences between Lean and ecologically oriented variables such as resource usage, energy consumption, and air pollution. The methodology is literature review evaluating the findings of research in this sphere. Besides the discussion of its principles and methods, current trends and challenges regarding lean production as a business model that supports eco-efficiency are presented. The implications of this study will allow executives to better recognize and simultaneously solve both the economic and environmental problems posed by their companies.",signatures:"Ruhet Genç",downloadPdfUrl:"/chapter/pdf-download/75839",previewPdfUrl:"/chapter/pdf-preview/75839",authors:[{id:"340234",title:"Prof.",name:"Ruhet",surname:"Genç",slug:"ruhet-genc",fullName:"Ruhet Genç"}],corrections:null},{id:"78284",title:"Circular and Lean Food Supply Chains",doi:"10.5772/intechopen.99769",slug:"circular-and-lean-food-supply-chains",totalDownloads:164,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Circular economy (CE) refers to the industrial economy that aims to achieve enriched sustainability through restorative objects and supply chain design. Many governments have put in place different initiatives in line with the CE. On the other hand, the term Lean operations refers to the reduction of the non-value adding activities and waste in a supply chain. The food sector has been criticized for its sustainability and circularity due to the high levels of food and packaging waste and at the same time the increasing costs. Although food supply chain entities have started to implement circular economy and lean practices, the current efforts do not seem to be sufficient to achieve a circular and lean food system. 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The approaches for the drug development of heart disease are majorly relying on the pathophysiology of the cellular mechanisms and inter and intracellular channels in the failing heart. Heart being an organ of extensively high energy demand and mitochondria being the powerhouse of the eukaryotic organisms, they are meant to be closely connected. Any change in mitochondrial function inevitably affects the health of the heart irrespective of the etiology. Recent advances in the field indicate that besides having a compromised powerhouse, mitochondrial malfunctioning accompanies certain pathogenic mechanisms leading to heart failure [2, 3]. Current therapies like ischemic pre- and postconditioning provide symptomatic benefit but do not address the abnormalities at a molecular level. Since the mitochondria play an important role in the pathophysiology of a failing heart, understanding its mechanism can potentially improve the approaches for the therapies for direct improvement of cardiac functions. Among the abnormalities shown by the mitochondria, ruptured electron transport chain, excessive formation of reactive oxygen species (ROS), perturbed ion homeostasis are the basic concerns [4]. An important and potential substrate for therapeutics in heart failure is mitochondrial channels [5]. In this chapter, we intend to discuss the available information about the mitochondrial channel with regards to its pathophysiological effects on heart health and their responses to the ischemic conditioning alongside the available agonist for the mitochondrial channel.
Due to high energy demand, the number of mitochondria in the heart cells is excessively high, with a daily production of approximately 65 kg ATP through oxidative phosphorylation [6]. In the neonatal cardiac myocytes, the mitochondria are highly motile in the cytosol generating energy through glycolysis and glucose metabolism. Whereas, in an adult myocyte the mitochondria have reduced motility, and energy generation occurs from the metabolism of fatty acid [7].
Mitochondria are known to arise billions of years ago through the engulfment of alpha proteobacteria by the precursors of modern eukaryotic cells and it evolved to become an essential multifunctional organelle [8]. Mitochondria are made up of an outer comparatively permeable and inner highly folded relatively impermeable lipid bilayer. The folded inner membrane with a high surface area contains the complexes for the generation and transportation of adenosine triphosphate (ATP) through oxidative phosphorylation. In the myocardial cells, the substrates are oxidized to produce acetyl coenzyme A, which in turn drives the Krebs cycle to produce nicotinamide adenine dinucleotide hydrogen (NADH) and flavin adenine dinucleotide (FADH2) in the mitochondrial matrix. The oxidation of NADH and FADH2 leads to the establishment of proton motive force later fetched by F1F0 ATP synthase to convert adenosine diphosphate (ADP) and inorganic phosphate to ATP [9].
In the process of energy production, approximately 2% of the electrons flowing in the electron transport cycle are reduced to form a superoxide anion which is reduced to H2O2 followed by H2O generation by antioxidant enzymes. Excessive production of these ROS is toxic to the cell, yet these natural byproducts of oxygen metabolism trigger a variety of oxygen sensing machinery including gene expression, however, the overload of ROS impairs the redox potential of the cell leading to various oxidative damages [10].
The dynamics of Ca2+, an important element to trigger various enzymatic processes and a second messenger for contractile functions, is also organized by mitochondria by either transmembrane Ca2+ transport or ROS-mediated signaling pathways [11]. In case of increased workload rapid mitochondrial Ca2+ uptake is facilitated by Ca2+ uptake channel for elevated ATP production. The elimination of Ca2+ from the mitochondrial matrix however is slower and mediated either directly by Na+/Ca2+ exchanger or indirectly by multiple mitochondrial K+ channels with unknown mechanisms [12].
Alongside the role as a life-supporting system, mitochondria can also trigger programmed cell death in the required conditions. The mitochondrial permeability transition pore (MPTP) opens in response to stress and leads to loss of membrane potential, which stops ATP production and release of cytochrome C and other mitochondrial protein causing necrosis and cell apoptosis [13]. In cases of heart failure mitochondria-induced cell death is an important mechanism. Here we intend to discuss important parameters of mitochondrial dysfunction which lead to heart failure, and therapeutic approaches to circumvent the situation.
In cardiac cells the energy consumption should meet the energy production rate on a beat-by-beat basis, failing which the stored energy cannot last more than a few seconds. In a pathological remodeling the oxidative metabolism switch from fatty acid metabolism to glycolysis, which only contributes less than 5% of the total ATP demand of an adult heart [14]. On the other hand, during pathological remodeling the required energy increases due to disturbed cardiac geometry, and impaired ATP homeostasis. Studies have shown that the mitochondrial mechanisms involved in pathological remodeling in efforts to restore the energy homeostasis eventually led to a vicious cycle that drives pathological remodeling towards heart failure. The most puzzling scenario suggests that in the failing heart the ATP content is largely maintained after an initial glitch, thus whether the heart failure occurs due to energy starvation or in efforts to fight that starvation is a question yet to be addressed. Further in-depth analysis of the mitochondrial mechanisms can clarify if the efforts of maintaining the energy hemostasis are either helpful or potentially worsen the failing heart.
The catalysis of degradative oxidation of the nutrients through anaerobic dehydrogenases is facilitated by the reduction of oxidized pyridine and flavin nucleotide like NAD(P+) and FAD. These coenzymes should be again reoxidized since they are non-replenishable and cannot permeate the cell membrane with the degradation rate. During an ischemic episode since the respiratory chain is impaired the oxidation of the above-stated substrates is also hampered, moreover, the NADH(H+) oxidation is carried out by lactate dehydrogenase. Therefore, the anaerobic glycolysis takes over as the only pathway for ATP synthesis provided the phosphocreatinine is depleted with the onset of ischemia. Therefore, in a failing heart the oxidative metabolism switch for alternative carbon sources such as glucose which can be beneficial due to increased ATP production and oxygen uptake but when it takes over the usual fatty acid metabolism the energy production is not sufficient for an adult heart [14]. Increased glycolysis causes anaplerosis, increased lactate production, triggers the heart to go into pathological remodeling, and also inhibits branched-chain amino acid (BCAA) catabolism, and causes the accumulation of BCAA. A hyperacetylation of mitochondrial protein has also been seen as a failing heart the cause of which is not clearly understood [15].
The decrease in ATP concentration causes an immense ionic imbalance across the cell cytoplasm leading to the lowering of the pH of the cell. The inhibition of Na+/K+ ATPase, Na+/H+, Na+/Ca2+ antiporters leads to an overload of Ca2+ inside the cells causing hypercontracture and triggering the irreversible opening of mitochondrial permeability transition pore (MPTP) [16]. The frequently converting ATP into ADP and phosphate seeps out of the cell which further contributes to reduced performance of the heart. Opening of only one pore causes frequent depolarization and triggers the opening of other pores, following which the rapid influx of small molecular weight solutes enters the mitochondrial matrix to compensate for the depolarization and causes the mitochondrial matrix to swell. The expansion of the inner mitochondrial membrane leads to the rupture of the outer membrane which releases proapoptotic proteins leading eventually to cell death. Therefore, it is believed that altering the MPTP pore opening can be helpful in the prevention of cardiac reperfusion and cell death [17].
During an ischemic episode, the release of ROS is formed under the physiological and pathological conditions within the mitochondria. In a regular respiratory chain reaction, 2–4% oxygen undergoes an univalent reaction and produces superoxide [4]. The superoxides that are formed at complex I and complex III level are rapidly transformed by metalloenzymes like superoxide dismutase into hydrogen peroxide. In the first minute, it is small but in a later stage, it increases dramatically, leading to the disruption of mitochondrial membrane potential. Therefore, the consequence of ROS formation has been linked to the opening of the MPTP channel leading to apoptosis. These episodes put together in series lead to a gradual and irreversible decline of the cell integrity.
The opening of MPTP can occur through all the factors mentioned here, such as an increase in Ca2+ ion, depolarization, increase in the ROS, and phosphate concentration [18]. Certain factors like a high concentration of H+, Mg2+, and ADP can counteract the MPTP opening and work as antagonists [19, 20]. On the contrary, in the condition of reperfusion, the change in the pH is recovered by the burst formation of ROS in the presence of Ca2+, which creates the most favorable condition for MPTP opening even though the antagonizing effect of membrane potential recovery occurred. In isolated mitochondria, the MPTP opens at a very high Ca2+ concentration which is practically not possible in vivo therefore the increased Ca2+ alone is not responsible for MPTP opening rather can be triggered by several processes like ROS generating Ca2+ dependent enzyme.
It is believed that to reduce the damage occurring in the heart cells in a prolonged ischemic episode, the heart cells can be trained beforehand through small and regulated episodes of either cardiac ischemia or reperfusion that resulted from ATP deprivation or concentration increase of ROS and Ca2+ (Figure 1). This method has been tested in dogs [21] and higher mammals including humans [22, 23]. This process is known as ischemic preconditioning (IpreC). Similarly, ischemic postcondition (IpostC) can also be done in a brief intermittent cycle after a severe event [24]. These are performed by natural or artificial biomolecules which will be discussed later in this chapter.
The ischemic/reperfused heart mitochondria in comparison to the cardioprotected mitochondria. In cardioprotected mitochondria MPTP and MCU channels are closed and mitoK channel is opened.
The process of IpreC and IpostC usually activates protein kinase C isozymes [25] and other kinases [26] whose roles in cardioprotection are very dicey, because as ε isozyme protects the mitochondrial function by activating ALDH2 aldehyde dehydrogenase which removes the lipid peroxidation products, Baines et al. showed that the translocation of ε isozyme prevents the opening of MPTP pore [27]. Whereas δ isozyme of protein kinase C increases the tissue injury by flawed perfusion of myocytes and inhibits ATP and pyruvate dehydrogenase regeneration [27]. Several mitochondrial pathways are activated in the conditioning process contributing significantly to the process of cardioprotection and therefore they are considered attractive pharmacological targets.
The multifaceted relationship of mitochondria with cell death makes it an ideal target for aiming to preserve cardiomyocytes viability. In the lack of oxygen during ischemia although the ATP synthesis cannot be restored yet can protect through decreasing ATP hydrolysis. Several self-defense mechanisms are triggered by ischemic preconditioning like the depolarization of mitochondrial matrix promotes F1F0 ATPase binding to its natural inhibiter Factor (IF) [29]. A similar effect has been shown by overexpressed the BCL-2 gene in mice hearts, to conclude that ATP hydrolysis is modulated by BCL-2 as well since the oligomycin addition did not possess any additional effect. BCL-2 is upregulated in the preconditioned heart and downregulated by ischemia and reperfusion [30]. However, the cardioprotective effect caused by preconditioning can be abolished by antisense nucleotide in a perfused rat heart [31]. Another way to prevent ATP hydrolysis is by MPTP inhibition, which presents a wide range of protective actions like maintaining Ca2+ homeostasis, NAD+ depletion prevention, and preventing the release of pro-apoptotic protein [20, 32, 33]. The preconditioned heart prevents the opening of MPTP pores conferring stress-tolerant condition of the cardiomyocytes [34, 35].
In addition to protective effects posed by MPTP inhibition, numerous studies have vouched for the supporting effect of the mitochondrial potassium channel, specially mitoKATP and calcium-dependent mitoKCa. The influx of K+ into the inner mitochondrial matrix causes depolarization, with pH increase and matrix swelling [36, 37, 38]. It is suggested that matrix swelling due to K+ uptake compensates for the contraction of the matrix caused by increased potential difference due to lack of oxygen. The K+ uptake and matrix swelling are suggested to increase the recovery of ATP concentration, by preventing the loss of substrate channeling which happened due to increased potential difference at the onset of reperfusion [39].
A sudden increase in the permeability of the solute in the inner mitochondrial membrane (IMM) is known as the permeability transition [16]. The MPTP was first described by Haworth and Hunter in 1979, who showed that the addition of high levels of calcium to bovine myocardial mitochondria induced a nonspecific increase in permeability of the inner mitochondrial membrane [40]. Although the occurrence of permeability transition and its inhibitor as adenine dinucleotide has been known since 1950 [41]. Our understanding of mitochondrial physiology and the acceptance of the pore theory of permeability transition is greatly attributed to the study of a mitochondrial channel.
The opening of the MPTP channel causes depolarization, blocks ATP synthesis, releases Ca2+, depletes pyridine nucleotide, inhibits respiration, causes matrix swelling, which subsequently leads to cytochrome C mobilization and outer mitochondrial membrane rupture which ultimately releases endonuclease G and apoptosis-inducing factor (AIF) and other proapoptotic protein to kill the cell (Figure 1) [42, 43]. It should be noted though, that this detrimental effect of MPTP opening occurs only when the pore opening is long-lasting [44]. Whereas the short-term opening, both in vivo and in vitro [45], is suggested to be involved in the physiological regulation of Ca2+ and the homeostasis of ROS [4], subsequently providing mitochondria a fast mechanism for Ca2+ release. According to a study performed on a mitochondria calcium uniporter (MCU), null mice had an equal I/R injury as the wildtype littermates overruling cyclophilin-D (CyPD) protection (Figure 1). It leads to challenging the established concept and awaits the molecular details of the myocardial reperfusion mechanism and the precise roles of the channels for answers to these contradicting observations. The potential role of MPTP opening in heart failure was recognized way before the discovery of the role of mitochondria in apoptosis.
Although the molecular nature and precise composition of MPTP remain unknown it is believed that some proteins regulate the function of MPTP like CyPD (Figure 1). After the observation that cyclosporin (CsA) is a potent inhibitor of MPTP opening [46, 47], Halestrap et al. demonstrated that it occurred due to an inhibition of a peptidyl-prolyl cis-trans isomerase PPIase in the matrix [48]. They further purified and demonstrated the protein to be CyPD, which is an 18 kDa matrix protein. A range of other CsA analogs and sanglifehrin A (SfA) that showed their potency in preventing MPTP opening also acted as inhibitors of PPIase of CyPD. On the other hand, the MPTP opening is also inhibited by ATP and ADP but their complexes with Mg2+ and other nucleotides like AMP, GTP, or GDP fail to show a similar effect, it is worth noting that none of them are transported by the adenine nucleotide translocase (ANT) [49]. Furthermore, the increased sensitivity of MPTP opening towards Ca2+ is attributed to the inhibition in the binding of the ATP and ADP with ANT either by depleting the matrix of adenine nucleotides or by modifying ANT by thiol [50]. Helstrap group developed a model for MPTP, where CyPD binds to ANT and they undergo conformational changes to induce pore formation under Ca2+ trigger, and they showed that matrix Ca2+ favored ‘C’ conformation for ANT. Several matrices facing glutamate and aspartate residues on ANT are present whose carboxyl groups might play the role of Ca2+ binding as there is no Ca2+ binding motif established on ANT [50]. Another data consistent with the model showed the coprecipitation of CyPD specifically with ANT and the bonding increases with rising oxidative stress and decreases with the introduction of CsA but not with inactive CsH analog [51, 52]. The crystal structure of bovine ANT1 [53] showed a constriction provided by 3 helices, block the channel and if these are rearranged by the change facilitated by CyPD, then an extensive conformational change might account for MPTP formation. Phosphate ion has been known as an MPTP activator and carboxyatractyloside (CAT) prevents ANT from binding the phenyl arsine oxide (PAO) column but still does not prevent MPTP activation, which suggests that PAO can have an additional MPTP activation site apart from the ANT. When CAT treated beef heart mitochondria was passed through the PAO column phosphate carrier protein (PiC) was bound to the column [54]. Pretreatment of the column with MPTP inhibitors like ubiquinone (UQo) prevents the PiC binding to the column which suggests a key role in MPTP formation. Other proteins have also been suggested to have the structural and regulatory role in MPTP formation like peripheral benzodiazepine receptor and voltage-dependent anion channel, hexokinase, creatinine kinase, BCL2 proteins, and Bcl 2 associated X (BAX) proteins may also be associated with MPTP, but which proteins eventually constitute the formation of the pore is still unknown [55, 56].
Recently, another theory of multiple pores in MPTP has been proposed. Studies have been supporting the potential roles of ANT, PiP, F1F0 ATP synthase, and CyPD to be inner membrane component but all of them has shown CsA sensitive permeability despite the genetic deletion of the responsible gene, which raises a question on the hypothesis and further investigation led to propose the multiple pore-forming mechanisms. Deletion of the C subunit of F1F0 ATP synthase showed that CsA induced MPTP synthesis showed much lower conductance as compared to wild-type MPTP [57]. This C-subunit lacking channel could be inhibited by an ANT inhibiter bongkrekic, therefore it was suggested that a classic MPTP was not formed in the knockout mitochondria. It was concluded that the MPTP formation could be enhanced through other proteins e.g. ANT in the lack of c-subunit. Another study proposed that dimer of F1F0 ATP synthase, ANT and PiC can assemble into synthasome complex, and it requires CyPD for disassembly into its components. They further suggest that ATP synthasome assembles and disassembles in high work conditions and MPTP formations respectively. Low ADP, high calcium enhancement leading to increase the membrane potential, and ROS formation trigger the disassembly of ATP synthasome leading to MPTP formation. Additional studies will be required to completely understand all the components of synthasome in generating MPTP [58].
As a result of its central role in myocardial infarction, MPTP poses itself as an obvious target for cardioprotection. A wide variety of cardioprotective protocols have been demonstrated to prevent MPTP opening during reperfusion. Certain drugs directly inhibit MPTP like CsA and SfA and their non-immunosuppressant derivatives like 4-methyl-val-CsA and D-3-MeAla-4-EtVal-CsA etc. and certain protocols that decrease oxidative stress and pH for inhibiting MPTP pore opening such as ischemic preconditioning [35] and ischemic postcondition [59], temperature preconditioning [60], Na+/H+ exchanger inhibiter like cariporide [61], mitochondrial ubiquinone antioxidants [62], the anesthetic propofol [63], urocortin [64], antioxidants including pyruvate [65].
The drugs that directly inhibit MPTP pose great value in protecting the heart during cardiac surgery, it has been shown that CsA improved cardiac performance following angioplasty treatment [66]. However, CsA and Sfa administration pose unwanted side effects because they interact with other cyclophilins like CypA moreover, their MPTP opening inhibition is overruled by the intensity of the pore opening stimulus [67]. This situation requires the development of new MPTP inhibitor drugs which can overcome these constraints. The development of new drugs requires structural insight into the MPTP pores.
The inner mitochondrial anion channel (IMAC) was the first mitochondrial channel to be identified using the patch-clamp method [68]. The pharmacological drug testing on the cardiomyocytes, for analysis of the mitochondrial matrix swelling, led to the discovery of its role in membrane potential perturbation. Its activity is promoted under stressed oxidizing conditions [69]. O’Rourke and co-workers proposed that the arrhythmias and electrophysiological alteration in cardiomyocytes are the results of disturbed membrane potential due to failed cellular mitochondrial network under oxidative stress [70]. The inhibition of IMAC mediated mitochondrial membrane potential oscillation with 4-chlorodiazepam showed a significant reduction and stabilization of the sarcolemmal action potential [71]. High-resolution optical action potential mapping showed that the introduction of 4-chlorodiazepam facilitates the restoration of action potential duration and prevents ventricular fibrillation. The thiol oxidants trigger the oscillation of membrane potential, glutathione, and NADH, which in turn increases the ROS concentration [72]. The inhibition of IMAC activity is triggered by the binding of 4-chlorodiazepam with benzodiazepine receptors. The inhibited IMAC preserves the membrane potential; however, the prohibited efflux of superoxide from IMAC further increases the ROS concentration [73]. The increasing ROS and decreasing glutathione concentration in the mitochondrial matrix trigger the opening of the MPTP pore, and therefore, IMAC can be considered as an instigator of MPTP opening [72].
The macromolecular structural assembly responsible for mitochondrial Ca2+ uptake machinery is known as the mitochondrial calcium uniporter (MCU) complex. It was initially assumed that an active uptake and passive release are required for the transport of Ca2+ across the inner mitochondrial membrane [74], but multiple groups showed that the uptake is energetically favored whereas efflux requires electrogenic ion-exchange [75].
Ca2+ uptake in mitochondria results from a single transport mechanism by a Ca2+ sensitive channel of mitochondria known as MCU (Figure 1). The molecular identification of the MCU protein complex which was closely connected to a comprehensive protein compendium MitoCarta was done in 2008 [76]. Following the establishment of a compendium Ca2+ sensing regulator, mitochondrial Ca2+ uptake 1(MICU1) was discovered in 2010 [77]. MICU1 was predicted to contain no transmembrane domain and was therefore not considered forming a pore. Later 40 kDa two transmembrane domains were identified termed MCU in 2011 [78, 79] followed by the identification of other regulatory subunits.
The concentration Ca2+ increases in the mitochondrial matrix during ischemia and reperfusion and this increase is proposed to activate MPTP opening [16]. Therefore, the inhibition of mitochondrial calcium uniporter is studied to reduce cell damage in I/R. Studies from MCU knockout mice in the germline [80] and MCU mutated gene [81], in both the cases the Ca2+ uptake was hindered leading to no MPTP opening, but neither of the situations reduced the size of cardiac infarct at the onset of I/R. In contrast, where the MCU was deleted after birth in adult hearts showed cardioprotection in an in vivo model [82]. The reason for this kind of difference is not very clear but apparently, the MCU knockout before birth could generate a more robust MPTP pore not regulated by CsA as well. Alongside MCU, the other two core structural components are mitochondrial calcium uniporter b MCUb and an ion transport component termed “essential MCU regulator” or EMRE. MCUb is closely related to MCU with 50% amino acid homology, containing two similar transmembrane domains linked with coiled-coil domain. On the other hand, EMRE is a 10 kDa protein span in the inner mitochondrial membrane that contains an aspartate-rich, highly conserved, C-terminal region, whose topology however is still unclear [83]. It was proposed by Mootha et al. that EMRE is required for Ca2+ channeling activity and also helps in keeping the MICU1/MICU2 intact to the MCU complex [84].
Altering the levels of regulators of MCU complex the calcium uptake can also be regulated in mitochondria, subsequently altering the susceptibility to MPTP-induced cell death. A mitochondria Ca2+ uptake protein1 (MICU1) mutation causing a loss of function in a human patient is associated with ataxia, attributed to mitochondrial Ca2+ overload [85, 86]. In a failing heart, an increase of MICU1 and Na+/Li+/Ca2+ exchanger (NCXL) has been observed to compensate for the Ca2+ overload [87]. MICU2 on the other hand has been observed to increase, with cardiovascular disease in both humans and mice, at the transcriptional level [88]. Mice with deletion of MICU2 showed a certain degree of diastolic dysfunction. The low ratio of MICU/MCU maintains a low threshold of calcium entry in mitochondria and the overexpression of MICU1 causes contractile dysfunction to the heart. Therefore, the rise in MICU1 and MICU2 with age and disease alters the susceptibility of calcium overload and MPTP inhibition.
In a cardiac muscle, constant rhythmic cycles of contraction are dependent on permanent uptake and release of Ca2+ in the cytoplasm and buffering organelles [89]. After a myocardial contraction, the removal of the Ca2+ from the cytoplasm is provided by Na+/Ca2+ exchanger (NCX) in the endoplasmic reticulum, on the other hand in non-muscle cells the cytosolic Ca2+ signals and Ca2+ buffering depends on mitochondrial Ca2+ uptake [90]. Although this mitochondrial Ca2+ uptake in cardiomyocytes possesses a very low MCU current and constitutes less than 1% of total Ca2+ uptake [89, 91], it plays a key role in coordinating between excitation and metabolism coupling [92]. In a healthy heart, two models of mitochondrial Ca2+ dynamics have been suggested by Cao et al., the first model suggests that Ca2+ concentration oscillates in a beat-to-beat manner in cardiomyocytes whereas, the second model emphasizes gradual Ca2+ uptake by cardiac mitochondria. On the contrary, in the damaged heart the Ca2+ mishandling within the mitochondria is well documented [93]. The MICU1 protein content is significantly low following I/R due to inhibition of translocase expression of the outer membrane. Furthermore, treatment attempts using siRNA on myocardial MICU1 aggravated the ischemic episode increasing tissue damage and depressing cardiac function due to apparent Ca2+ overload [87].
As it is quite evident that the uncontrolled influx of Ca2+ is disastrous for cardiomyocytes, and MCU is the major route for Ca2+ entry. Therefore, alteration in the expression of MCU can be a promising target for cardioprotection. For the inhibition of MCU ruthenium red and its derivatives are generally used, however, ruthenium red has nonspecific activity towards other ion channels [94] as well which does not make it a suitable inhibitor and prevents it from usage as a therapeutic agent. Recently, two new highly selective MCU inhibitors were developed one is DS16570511 prevents Ca2+ overload and raises cardiac contractility without affecting heart rate [95]. The second one is Ru265 is negligibly toxic and prevents hypoxia in the cell model [96]. Mitoxanthrone, an anticancer drug that showed its efficiency in inhibiting MCU [97], similarly kaempferol known as an anticancer [98] and cardioprotective drug [99] could prevent Ca2+ created arrhythmias [100]. These can be promising drugs in preventing Ca2+ related risks to cardiomyocytes but they require more animal study, and careful modeling and validation before adapting as therapeutics.
On one side where the opening of mitochondrial mega channels like MPTP and Ca2+ uniporter represents a hallmark of cell death, on the other hand, the transport of K+ through ion channels is known to play a central role in neural and cardioprotection [101, 102, 103]. The membrane potential and permeability of the inner mitochondrial membrane are strictly controlled for efficient ATP production. The presence of an electrophoretic pathway for entry and antiporter mechanism for the exit of K+ has been well established and they critically regulate the mitochondrial volume and function. The transport of K+ ions from the cytosol to the mitochondrial matrix is carefully conducted through ion channels by utilizing electrogenic transport, where the proton ejection by the electron transport system generates enough membrane potential for the influx of K+. There are four kinds of mitochondrial K+ channels (Figure 2) present in the inner membrane the ATP regulated [104], Ca2+ regulated [105], Twin pore TASK channel [106], and voltage-gated Kv1.3 potassium channel [107]. These channels resemble the plasma membrane potassium channels in their basic biophysical properties and are regulated to avoid the membrane potential collapse.
Mitochondrial potassium channels (a) voltage-gated potassium channels (Kv 1.3, Kv 1.1, Kv 1.5), (b) small and large conductance mitoKATP channel (IKCA, BKCa), (c) ATP sensitive K+ channel, (d) twin pore K+ channel. mitoKATP and mitoBKCa having extensively studied for cardioprotection.
Several mitochondrial K+ channels (Figure 2) have been discovered so far but ATP sensitizing uptake of K+ has gazed maximum attention. The cardiac ischemic conditioning was first believed to be working on KATP of the plasma membrane counterpart but based on pharmacological analysis with channel openers and inhibitors shown to affect mitochondrial KATP channel. The mitoKATP channel was first identified in rat liver mitochondria using the patch-clamp method [91] and was later found in the inner mitochondrial membrane [108, 109]. They are situated at the crossroad of metabolism and membrane sensitivity. The molecular identities of a mitoKATP were recently determined by Angela Paggio et al. [110], which is similar to its plasma membrane counterparts that consisting of pore-forming potassium channel CCDC51 (MITOK) and ATP-binding cassette (ABC) transporter ABCB8 (MITOSUR); however, the detailed assembly and function mechanism is still unknown due to the missing of structural information. The plasma membrane KATP is heterooctameric, containing four inward rectifying potassium channel subunits of Kir6.1 and four sulfonylurea receptor subunits, which belong to the ABC transporter family [111]. Whether this newly identified mitoKATP is occupying a similar octameric assembly as the plasma membrane KATP is still unknown and moreover, it may not present the only version of mitoKATP as channels such as Kir6.1 has also been suggested in the formation of mitoKATP [28]. Nevertheless, they are believed to play a central role in cardioprotection, since the bizarre method of cardioprotection called ischemic conditioning was introduced. Ischemic preconditioning was first observed with plasma membrane using KATP channels as effectors, but later mitochondrial potassium channel became an interesting target for the same. The pathway involves activating the protein kinase and generating ROS, but the precise role of mitoKATP is not very well established. Therefore, evidence of molecular structure for the mitoKATP will subside the pharmacology-based arguments of its existence and role in the process of preconditioning. According to a study by Peng Duan et al., mitoKATP channel opening is helpful in the optimal expression of protein kinase B (p-AKT) and forkhead box protein O1 (pFoxo1) in an insulin-resistant cell. The increased p-Foxo1 is phosphorylated by p-AKT, reducing its transcriptional efficiency, and transferred out of the nucleus, and prevents the expression of pro-apoptotic protein, thereby preventing apoptosis [112].
A study done by Garlid et al. in 2006, showed that the K+ ion uptake in the mitochondria leads to increased ROS production as they explain that the opening of the mitoKATP channel will lead to a small amount of K+ uptake but this lowered potential will increase the matrix volume and pH by a persistent steady state. Valinomycin was used to induce the mitoKATP opener and an increased pH caused an increased ROS production, when the acetic acid influx increased for compensation of the alkaline matrix the ROS production also reduced proving that the alkalinity is a cause for ROS production. It was also proved by them that the ROS was generated from the complex I of the electron transport system [113].
These channels were first discovered in the glioma cell line LN-229 and have been extensively studied in the brain and cardiac cells since then [105]. The calcium-activated potassium channel is of two types small and intermediate conductance K+ channel and large or big conductance K+ channel. The small and intermediate channels are only calcium-dependent and not voltage-dependent they possess calmodulin for the Ca2+ binding at the C-terminal region. Their major function is promoting proliferation and migration of dendritic cells and smooth muscle [114].
The first evidence of its presence in the inner mitochondrial membrane was found in the late 90s by Siemen and coworkers although showing that it possesses a conductance of 300 pS [105]. Its role in protecting the heart from ischemic insult was first discovered by Xu et al. and their structural characterization in the plasma membrane indicates that it originates from potassium calcium-activated channel subfamily M alpha 1 (Kcnma1) gene containing extracellular N terminus and intracellular C-terminus [115]. It has been proven in 2013 that the BKCa pore-forming alpha subunits are encoded by the same genes (Kcnma1) as the basis of why they possess the same physiological properties [116].
The big conductance Ca2+ sensitive K+ channel also known as MitoBKCa on the other hand is intuitive to voltage and mechanical stress alongside Ca2+ sensitivity. The knockout experiments have proven for the MitoBKCa channels to have a cardioprotective effect by reversing the ROS production and opening MPTP. It has also been shown that these channels form a multiprotein complex with several proteins involved in apoptotic machinery [117].
mitoBKCa channel [118] represent themselves as a key pathophysiological target due to their sensitivity towards calcium, voltage, and a range of cellular components. Several small molecular openers for BKCa and pharmacological agents have provided very insightful information to decipher the role of BKCa channel. Pharmacological agents like NS1619 and NS11021 have been used to activate BKCa can potentially play a vital role in cardioprotection. However, they fail to reach the clinical applications due to their non-specificity [119, 120, 121, 122]. Although it is posing a great deal of difficulty in developing the BKCa activators, it becomes essential considering that expression of BKCa is vital for cardioprotection [116, 123].
The first representation BKCa playing an essential role in cardioprotection from I/R injury was performed by using NS1619, whose effect was blocked by praxilline [115]. A 3 mM NS1619 preconditioning showed an improved reduction of infarct size, possibly by modulated Ca2+ and ROS concentration [117]. BKCa mediated cardioprotection involves ROS, Ca2+, and MPTP and their interplay. It is anticipated that reduction of deleterious ROS through BKCa activation prevents the excess release of Ca2+ from the endoplasmic reticulum subsequently reducing the influx and overload in mitochondria preventing the cell from injury.
These are the most diverse family of K+ channels. They are grouped into 12 families comprising 40 of the 90 genes present in human cells [124]. These channels mostly consist of six transmembrane helices (S1-S6) where two of them (S5-S6) form the loop and four of them are proceedings to the loop (S1-S4). The fourth positively charged loop senses the change in the membrane potential. These channels have a wide variety and therefore, they represent a fine regulation of K+ flux in the homeostasis and pathological processes. The mitochondrial counterpart mitoKv1.3 is found in lymphocytes [125] and many carcinogenic cells [126, 127], they present similar physiological functions as the plasma membrane counterpart and, they are translated from the same gene. mitoKv1.3 is a target for pro-apoptotic protein Bax [128]. Their complex prevents the opening of mitoKv1.3 channel for K+ influx and therefore causes the disturbance in membrane potential and eventually leads to apoptotic cell death. Therefore, mitoKv1.3 has represented itself as a new tool for targeted cell death for many tumor cells by triggering mitochondria-induced apoptosis. Their presence in cardiac cells has not been reported. Similar to Kv1.3 other potassium channels like Kv1.1 and Kv1.5 have also shown dual origin in both mitochondrial and plasma membrane causing cell apoptosis by targeting macrophages [129, 130].
The mitochondrial TASK-3 was discovered in human keratinocyte HeCaT cells using the patch-clamp method [131]. It shows similarity with its plasma membrane counterpart and its activity is inhibited at acidic pH [132]. Lidocaine and low pH completely block the task channel activity in mitochondria. TASK-3 is essential for the survival of WM35 melanoma cells [133] but its activity in the mitochondrial dysfunction in cardiac reperfusion is not known.
The above discussions have made it clear that since the inner mitochondrial channels regulate the onset of apoptosis and cell death, they present an important target for cardioprotective therapeutics. Not only mitochondrial potassium channel but also MPTP, MCU, connexin-43, and protein uncoupling have shown their potential roles in reducing myocardial infarct size and preventing heart failure.
A sudden opening of MPTP can be triggered through a high concentration of Ca2+, high amount of ROS production, and decrease in mitochondrial membrane potential, which results in the loss of proton gradient appearing as an uncoupling effect, which prevents ATP formation and promotes its hydrolysis [41]. Subsequently, the proton gradient utilizes the Ca2+ uptake and causes the matrix swelling as an approach of the MPTP to prevent the detrimental rise in Ca2+ in the mitochondrial matrix [134]. It is known that opening of MPTP for a short duration can proceed without affecting cell viability and can also contribute to cardioprotection through participating in pre ischemic conditioning and it later prevents the opening of MPTP pore during ischemic reperfusion preventing cell damage and the onset of heart failure [17]. Although the evidence to support its cardioprotective functions is majorly based on the pharmacology and genetic observation that avoided MPTP opening. It has been shown that the administration of cyclosporin A shows a cardioprotective effect by preventing MPTP opening in the mice model; however, the results are mixed for the large mammalian model [135].
As mentioned earlier an increase in the Ca2+ concentration contributes to the opening of the MPTP channel, it is also necessary to mention that the Ca2+ is essential for the key enzyme activation in the oxidation of the substrates that fuel the respiratory chain, followed by ATP formation. It is very unfortunate that despite the advancement in technologies we are still unable to determine the physiological and pathological concentration of Ca2+ in the mitochondrial matrix [136]. Nevertheless, the Ca2+ homeostasis is maintained within the mitochondrial matrix by the uptake of Ca2+ through uniporters and the release is catalyzed by Na+/Ca2+ exchanger. The understanding of the molecular nature of Ca2+ uniporter has advanced our knowledge about Ca2+ homeostasis. The deletion of mitochondrial calcium uniporter gene from the embryonic and adult mice has shown completely contradicting results and the reasons of which have not yet been fully understood. However, the results that appeared in adult mice fully support the role of calcium overload leading to MPTP opening and eventually cell death. This is further supported by the Na+/Ca2+/Li+ exchanger knockout mice which showed the overload of Ca2+ leading to MPTP opening on the onset of ischemic reperfusion leading to cell death. Therefore, the drugs that intend to target Ca2+ uniporter for therapeutics need to validate the contrast effects before large animal and clinical testing [137].
Connexin43(Cx43) is a well-known channel for the intercellular connections by forming the gap junctions, but apart from the plasma membrane occurrence, they are also known to be present in cellular organelle like subsarcolemmal mitochondria [138], nucleus [139], and exosomes [140]. Cx43 plays an important role in ischemic-reperfusion injury and its prevention. According to pharmacological evidence the concentration of Cx43 increases with the introduction of diazoxide DZX or fibroblast growth factor 2 to prevent myocardial injury, but this increase is not observed after the ischemic preconditioning protocol [141]. It also interacts with the mitochondrial potassium channel [141] and regulates nitric oxide formation. The role of Cx43 is certain in cardioprotection but the exact mechanism and function remain to be elucidated.
At last, the presence of several mitochondrial K+ channels and their activity in the failing heart presents them as a crucial target in the therapeutics of myocardial dysfunction. The K+ uptake and release play a central role in the maintenance of mitochondrial matrix volume. The electrophoretic influx of K+ is balanced by the K+/H+ antiporter [142]. Valinomycin triggers the uncontrolled K+ influx disturbing the mitochondrial polarization and causing the swelling of the matrix. The function of potassium channels is basically to maintain the matrix volume. Initially, surface K+ channel was suggested to play an essential role in ischemic pre and postconditioning but later when diazoxide (DXZ), which was involved in cardioprotection of non-contractable heart, did not show any effect on surface K+ channel, whereas drugs that were only targeting surface K+ did not show cardioprotective effect. On the contrary, the isolated mitochondria showed restored activity of ATP inhibited flux and showed inhibition caused by 5-hydroxydecanoate (5HD) [143]. This shifts the attention to the mitochondrial K channel for cardioprotection but ever since the DXZ and 5HD also affect mitochondrial physiology in general it requires the molecular structure information and in vivo attempts for concrete statements. The structural information will provide tools for determining its exact function in myocardial ischemia/reperfusion in a failing heart, Ca2+ transport and MPTP opening, and protein involved in ROS formation, followed by improving therapeutic approaches [144]. Similar to the ATP activated K+ channel, Ca2+ and voltage-activated channels are also pharmacologically proven to play a similar role as mitoKATP, the ischemic conditioning protocol triggers the formation of protein kinase C which is helpful in an increased opening mitoKCa channel.
The strategies used to protect the heart from opening MPTP and mitochondrial calcium uniporter pores and in the case of ischemia conditioning, the opening of mitoKATP and BKCa channel plays a vital role in the cardioprotection. CsA is a well-known desensitizer for MPTP, but it did not prove to be the best option in clinical trials [66]. CsA exerts its activity by binding to CyPD, but in cases of intense stimuli, the pore opening becomes independent of CyPD. Therefore, there is a need of developing more pharmacological agents that can directly inhibit the MPTP openings, but they require further information about the structural insight of the pore. Although CyPD activates pore opening the complete mechanism is still unclear. Similarly, although it is evident that ROS and Ca2+ influence the MPTP opening but without knowing the structural details of MPTP we fail to conclude how they do so.
Mitochondrial calcium regulates a range of myocyte functions alongside energy production like cell division and trophism. With the development of MCU structures over the years, they have emerged as a very important target for cardioprotection, but the development of a reliable drug is still in process. Potassium channels are also widely accepted as an important target and are closely linked to modulating the apoptotic process. This information is present due to the pharmacology of the channel openers and inhibitors. Very limited knowledge is present to show concrete evidence. The molecular structure can be helpful in understanding and curing several mitochondria-associated diseases.
The inhibition of MPTP channel opening and the mitoK channel both elicit the cardioprotection and are likely to be related. Uptake of K+ through mitoK decreased the mitochondrial membrane potential which reduces the mitochondrial Ca2+, which in turn decreases the possibility of MPTP opening. Along with ATP production, and ROS regulation, mitochondrial channels like MPTP, Ca2+ channel, and mitoK channels are established to play a crucial role in cardioprotection. The mechanism, however, for their connection and coordination with each other in the process of cardioprotection is far from conclusive.
Recent attempts to translate cardioprotective strategies that target some of these mitochondrial ion channels have been hugely disappointing, and the translational of these strategies in clinical settings have not been successful. Several drugs have been tested on various animal models that have shown certain cardioprotective mechanisms. However, the lack of knowledge about the underlying mechanism of protective actions needs a lot of following studies to design modulators specific for mitochondrial channels with regards to cardioprotection in human trials. In the light of studies available, we still have a long way to go in the depth of the cardioprotective mechanism.
Conclusively, heart failure is an outcome of cardiac injury that originated due to a variety of etiologies and denotes a complex clinical syndrome. Several mitochondrial channels associated mechanisms have been recognized that drive the depletion of cardiomyocytes before cell death. These observations not only provide a link of overall heart health with mitochondrial channel opening and closing but also inspires therapeutic approaches. The core molecular identity of some mitochondrial channels like MCU and mitoKATP are discovered recently, whereas most mitochondrial potassium channels are in their intermediate state. These channels act as switches to control the development of ischemic injury either towards recovery or the loss of viability. The progress towards understanding the molecular identity and mechanism of channel opening and inhibition will help to translate the experimental approaches into promising therapeutic development to combat a deadly health concern.
We thank Dr. Nileshkumar Dubey for his help with the figures. Figure 1 was created with Biorender.com.
The authors declare no conflict of interest.
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This study therefore examined land acquisition and use in Nigeria within the context of food and livelihood security. The chapter used secondary data obtained from the World Bank website, National Bureau of Statistics (NBS) and other sources. It was found that there are gender, location and income-group considerations in the allocation of land in Nigeria. While the urban land market is relatively more formal, the rural land market is informal and the transactions were not documented in most cases. The study found that bureaucratic bottlenecks, high cost of registering land and long registration procedures, and inconsistent policy regimes impede the development of land market in Nigeria. Based on the findings of the study, it was recommended that the government should reduce and make the processes to be completed in registering lands in Nigeria easier. The Land Use Act 1978 should be amended to capture the prevailing realities around customary laws and informal markets. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. 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He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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Silva, Eliete A. Alvin, Lais S. de Jesus, Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins, Diógenes Meneses, Marcela R. Lemes, Rhanoica O. Guerra, Marcos V. da Silva, Carlo J.F. de Oliveira, Virmondes Rodrigues Junior, Renata M. Etchebehere, Fabiane C. de Abreu, Bruno G. Lucca, Sanívia A.L. Pereira, Rodrigo C. Rosa and Noelio O. 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Paul",slug:"organoids-and-commercialization",totalDownloads:33,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81412",title:"Mathematical Morphology and the Heart Signals",doi:"10.5772/intechopen.104113",signatures:"Taouli Sidi Ahmed",slug:"mathematical-morphology-and-the-heart-signals",totalDownloads:19,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81360",title:"Deep Learning Algorithms for Efficient Analysis of ECG Signals to Detect Heart Disorders",doi:"10.5772/intechopen.103075",signatures:"Sumagna Dey, Rohan Pal and Saptarshi Biswas",slug:"deep-learning-algorithms-for-efficient-analysis-of-ecg-signals-to-detect-heart-disorders",totalDownloads:31,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"81294",title:"Applications of Neural Organoids in Neurodevelopment and Regenerative Medicine",doi:"10.5772/intechopen.104044",signatures:"Jing Gong, Jiahui Kang, Minghui Li, Xiao Liu, Jun Yang and Haiwei Xu",slug:"applications-of-neural-organoids-in-neurodevelopment-and-regenerative-medicine",totalDownloads:25,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81318",title:"Retinal Organoids over the Decade",doi:"10.5772/intechopen.104258",signatures:"Jing Yuan and Zi-Bing Jin",slug:"retinal-organoids-over-the-decade",totalDownloads:41,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Organoids",coverURL:"https://cdn.intechopen.com/books/images_new/11430.jpg",subseries:null}},{id:"81068",title:"Characteristic Profiles of Heart Rate Variability in Depression and Anxiety",doi:"10.5772/intechopen.104205",signatures:"Toshikazu Shinba",slug:"characteristic-profiles-of-heart-rate-variability-in-depression-and-anxiety",totalDownloads:20,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}}]},subseriesFiltersForOFChapters:[{caption:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",value:9,count:1,group:"subseries"},{caption:"Bioinformatics and Medical Informatics",value:7,count:13,group:"subseries"}],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:302,paginationItems:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. 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At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. 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In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. 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He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. 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