General properties of SEs and SEls and genomic location of the encoding genes.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\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:"5416",leadTitle:null,fullTitle:"Cloud Computing - Architecture and Applications",title:"Cloud Computing",subtitle:"Architecture and Applications",reviewType:"peer-reviewed",abstract:"In the era of Internet of Things and with the explosive worldwide growth of electronic data volume, and associated need of processing, analysis, and storage of such humongous volume of data, it has now become mandatory to exploit the power of massively parallel architecture for fast computation. Cloud computing provides a cheap source of such computing framework for large volume of data for real-time applications. It is, therefore, not surprising to see that cloud computing has become a buzzword in the computing fraternity over the last decade. This book presents some critical applications in cloud frameworks along with some innovation design of algorithms and architecture for deployment in cloud environment. It is a valuable source of knowledge for researchers, engineers, practitioners, and graduate and doctoral students working in the field of cloud computing. It will also be useful for faculty members of graduate schools and universities.",isbn:"978-953-51-3244-8",printIsbn:"978-953-51-3243-1",pdfIsbn:"978-953-51-4797-8",doi:"10.5772/62794",price:119,priceEur:129,priceUsd:155,slug:"cloud-computing-architecture-and-applications",numberOfPages:140,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"8ae44907e10133e5796c0dcd01234da8",bookSignature:"Jaydip Sen",publishedDate:"June 14th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5416.jpg",numberOfDownloads:12665,numberOfWosCitations:12,numberOfCrossrefCitations:17,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:25,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:54,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 31st 2016",dateEndSecondStepPublish:"April 21st 2016",dateEndThirdStepPublish:"July 26th 2016",dateEndFourthStepPublish:"October 24th 2016",dateEndFifthStepPublish:"November 23rd 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"9",totalChapterViews:"0",totalEditedBooks:"7",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"585",title:"Cloud Computing",slug:"cloud-computing"}],chapters:[{id:"54159",title:"State-of-the-Art Antenna Technology for Cloud Radio Access Networks (C-RANs)",doi:"10.5772/67352",slug:"state-of-the-art-antenna-technology-for-cloud-radio-access-networks-c-rans-",totalDownloads:3160,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:0,abstract:"The cloud radio access network (C-RAN) is one of the most efficient, low-cost, and energy-efficient radio access techniques proposed as a potential candidate for the implementation of next-generation (NGN) mobile base stations (BSs). A high-performance C-RAN requires an exceptional broadband radio frequency (RF) front end that cannot be guaranteed without remarkable antenna elements. In response, we present state-of-the-art antenna elements that are potential candidates for the implementation of the C-RAN’s RF front end. We present an overview of C-RAN technology and different types of planar antennas operating at the future proposed fifth-generation (5G) bands that may include the following: (i) ultra-wide band (UWB) (3–12 GHz), (ii) 28/38 GHz, and (iii) 60-GHz radio. Further, we propose different planar antennas suitable for the implementation of C-RAN systems. We design, simulate, and optimize the proposed antennas according to the desired specifications covering the required frequency bands. The key design parameters are calculated, analyzed, and discussed. In our research work, the proposed antennas are lightweight, low-cost, and easy to integrate with other microwave and millimeter-wave (MMW) circuits. We also consider different implementation strategies that can be helpful in the execution of large-scale multiple-input multiple-output (MIMO) networks.",signatures:"Waleed Tariq Sethi, Abdullah Alfakhri, Muhammad Ahmad Ashraf,\nAmr G. Alasaad and Saleh Alshebeili",downloadPdfUrl:"/chapter/pdf-download/54159",previewPdfUrl:"/chapter/pdf-preview/54159",authors:[{id:"189378",title:"Dr.",name:"Muhammad Ahmad",surname:"Ashraf",slug:"muhammad-ahmad-ashraf",fullName:"Muhammad Ahmad Ashraf"},{id:"190463",title:"Ph.D. Student",name:"Waleed",surname:"Sethi",slug:"waleed-sethi",fullName:"Waleed Sethi"},{id:"190464",title:"BSc.",name:"Abdullah",surname:"Alfakhri",slug:"abdullah-alfakhri",fullName:"Abdullah Alfakhri"},{id:"190466",title:"Dr.",name:"Amr",surname:"Alasaad",slug:"amr-alasaad",fullName:"Amr Alasaad"},{id:"194124",title:"Prof.",name:"Saleh",surname:"Alshebeili",slug:"saleh-alshebeili",fullName:"Saleh Alshebeili"}],corrections:null},{id:"53334",title:"Cloud Computing for Next-Generation Sequencing Data Analysis",doi:"10.5772/66732",slug:"cloud-computing-for-next-generation-sequencing-data-analysis",totalDownloads:4378,totalCrossrefCites:7,totalDimensionsCites:14,hasAltmetrics:0,abstract:"High-throughput next-generation sequencing (NGS) technologies have evolved rapidly and are reshaping the scope of genomics research. The substantial decrease in the cost of NGS techniques in the past decade has led to its rapid adoption in biological research and drug development. Genomics studies of large populations are producing a huge amount of data, giving rise to computational issues around the storage, transfer, and analysis of the data. Fortunately, cloud computing has recently emerged as a viable option to quickly and easily acquire the computational resources for large-scale NGS data analyses. Some cloud-based applications and resources have been developed specifically to address the computational challenges of working with very large volumes of data generated by NGS technology. In this chapter, we will review some cloud-based systems and solutions for NGS data analysis, discuss the practical hurdles and limitations in cloud computing, including data transfer and security, and share the lessons we learned from the implementation of Rainbow, a cloud-based tool for large-scale genome sequencing data analysis.",signatures:"Shanrong Zhao, Kirk Watrous, Chi Zhang and Baohong Zhang",downloadPdfUrl:"/chapter/pdf-download/53334",previewPdfUrl:"/chapter/pdf-preview/53334",authors:[{id:"176364",title:"Dr.",name:"Shanrong",surname:"Zhao",slug:"shanrong-zhao",fullName:"Shanrong Zhao"}],corrections:null},{id:"54076",title:"Green-Aware Virtual Machine Migration Strategy in Sustainable Cloud Computing Environments",doi:"10.5772/67350",slug:"green-aware-virtual-machine-migration-strategy-in-sustainable-cloud-computing-environments",totalDownloads:1687,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"As cloud computing develops rapidly, the energy consumption of large-scale datacenters becomes unneglectable, and thus renewable energy is considered as the extra supply for building sustainable cloud infrastructures. In this chapter, we present a green-aware virtual machine (VM) migration strategy in such datacenters powered by sustainable energy sources, considering the power consumption of both IT functional devices and cooling devices. We define an overall optimization problem from an energy-aware point of view and try to solve it using statistical searching approaches. The purpose is to utilize green energy sufficiently while guaranteeing the performance of applications hosted by the datacenter. Evaluation experiments are conducted under realistic workload traces and solar energy generation data in order to validate the feasibility. Results show that the green energy utilization increases remarkably, and more overall revenues could be achieved.",signatures:"Xiaoying Wang, Guojing Zhang, Mengqin Yang and Lei Zhang",downloadPdfUrl:"/chapter/pdf-download/54076",previewPdfUrl:"/chapter/pdf-preview/54076",authors:[{id:"188353",title:"Prof.",name:"Xiaoying",surname:"Wang",slug:"xiaoying-wang",fullName:"Xiaoying Wang"},{id:"194512",title:"Ms.",name:"Guojing",surname:"Zhang",slug:"guojing-zhang",fullName:"Guojing Zhang"},{id:"194513",title:"Ms.",name:"Mengqin",surname:"Yang",slug:"mengqin-yang",fullName:"Mengqin Yang"}],corrections:null},{id:"54459",title:"M-ary Optical Computing",doi:"10.5772/67351",slug:"m-ary-optical-computing",totalDownloads:1646,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The era of cloud computing has fuelled the increasing demand on data centers for high-performance, high-speed data storage and computing. Digital signal processing may find applications in future cloud computing networks containing a large sum of data centers. Addition and subtraction are considered to be fundamental building blocks of digital signal processing which are ubiquitous in microprocessors for arithmetic operations. However, the processing speed is limited by the electronic bottleneck. It might be valuable to implement high-speed arithmetic operations of addition and subtraction in the optical domain. In this chapter, recent results of M-ary optical arithmetic operations for high base numbers are presented. By exploiting degenerate and nondegenerate four-wave mixing (FWM) in highly nonlinear fibers (HNLFs), graphene-assisted optical devices, and silicon waveguide devices, various types of two-/three-input high-speed quaternary/octal/decimal/hexadecimal optical computing operations have been demonstrated. Operation speed up to 50 Gbaud of this computing approach is experimentally examined. The demonstrated M-ary optical computing using high base numbers may facilitate advanced data management and superior network performance.",signatures:"Jian Wang and Yun Long",downloadPdfUrl:"/chapter/pdf-download/54459",previewPdfUrl:"/chapter/pdf-preview/54459",authors:[{id:"174233",title:"Prof.",name:"Jian",surname:"Wang",slug:"jian-wang",fullName:"Jian Wang"},{id:"189711",title:"Dr.",name:"Yun",surname:"Long",slug:"yun-long",fullName:"Yun Long"}],corrections:null},{id:"53772",title:"Networking Solutions for Integrated Heterogeneous Wireless Ecosystem",doi:"10.5772/67084",slug:"networking-solutions-for-integrated-heterogeneous-wireless-ecosystem",totalDownloads:1797,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"As wireless communications technology is steadily evolving to improve the offered connectivity levels, additional research on emerging network architectures is becoming timely to understand the applicability of both traditional and novel networking solutions. This chapter concentrates on the utilization of cloud computing techniques to construct feasible system prototypes and demonstrators within the rapidly maturing heterogeneous wireless ecosystem. Our first solution facilitates cooperative radio resource management in heterogeneous networks. The second solution enables assisted direct connectivity between proximate users. The contents of the chapter outline our corresponding research and development efforts as well as summarize the major experiences and lessons learned.",signatures:"Roman Florea, Aleksandr Ometov, Adam Surak, Sergey Andreev\nand Yevgeni Koucheryavy",downloadPdfUrl:"/chapter/pdf-download/53772",previewPdfUrl:"/chapter/pdf-preview/53772",authors:[{id:"189268",title:"Dr.",name:"Sergey",surname:"Andreev",slug:"sergey-andreev",fullName:"Sergey Andreev"},{id:"194651",title:"Mr.",name:"Roman",surname:"Florea",slug:"roman-florea",fullName:"Roman Florea"},{id:"194652",title:"Mr.",name:"Aleksandr",surname:"Ometov",slug:"aleksandr-ometov",fullName:"Aleksandr Ometov"},{id:"194653",title:"Mr.",name:"Adam",surname:"Surak",slug:"adam-surak",fullName:"Adam Surak"},{id:"194654",title:"Prof.",name:"Yevgeni",surname:"Koucheryavy",slug:"yevgeni-koucheryavy",fullName:"Yevgeni Koucheryavy"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2263",title:"Applied Cryptography and Network Security",subtitle:null,isOpenForSubmission:!1,hash:"07634e142c90c16ba2a873e2e45d2cd0",slug:"applied-cryptography-and-network-security",bookSignature:"Jaydip Sen",coverURL:"https://cdn.intechopen.com/books/images_new/2263.jpg",editedByType:"Edited by",editors:[{id:"4519",title:"Prof.",name:"Jaydip",surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1778",title:"Cryptography and Security in Computing",subtitle:null,isOpenForSubmission:!1,hash:"62c15d873f53e3d996a21ab0821688f3",slug:"cryptography-and-security-in-computing",bookSignature:"Jaydip Sen",coverURL:"https://cdn.intechopen.com/books/images_new/1778.jpg",editedByType:"Edited by",editors:[{id:"4519",title:"Prof.",name:"Jaydip",surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3412",title:"Theory and Practice of Cryptography and Network Security Protocols and Technologies",subtitle:null,isOpenForSubmission:!1,hash:"edbd5d0f991597aa78defb420d03f547",slug:"theory-and-practice-of-cryptography-and-network-security-protocols-and-technologies",bookSignature:"Jaydip Sen",coverURL:"https://cdn.intechopen.com/books/images_new/3412.jpg",editedByType:"Edited by",editors:[{id:"4519",title:"Prof.",name:"Jaydip",surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6462",title:"Internet of Things",subtitle:"Technology, Applications and Standardization",isOpenForSubmission:!1,hash:"0db33037b03f025bd97ce988f4ab90c2",slug:"internet-of-things-technology-applications-and-standardization",bookSignature:"Jaydip Sen",coverURL:"https://cdn.intechopen.com/books/images_new/6462.jpg",editedByType:"Edited by",editors:[{id:"4519",title:"Prof.",name:"Jaydip",surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10651",title:"Machine Learning",subtitle:"Algorithms, Models and Applications",isOpenForSubmission:!1,hash:"6208156401c496e0a4ca5ff4265324cc",slug:"machine-learning-algorithms-models-and-applications",bookSignature:"Jaydip Sen",coverURL:"https://cdn.intechopen.com/books/images_new/10651.jpg",editedByType:"Edited by",editors:[{id:"4519",title:"Prof.",name:"Jaydip",surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8368",title:"Computer and Network Security",subtitle:null,isOpenForSubmission:!1,hash:"40b3cd1cd3de504736186805106eed6b",slug:"computer-and-network-security",bookSignature:"Jaydip Sen",coverURL:"https://cdn.intechopen.com/books/images_new/8368.jpg",editedByType:"Edited by",editors:[{id:"4519",title:"Prof.",name:"Jaydip",surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6696",title:"Cloud Computing",subtitle:"Technology and Practices",isOpenForSubmission:!1,hash:"69c2a63622364c3becf0792ddf15d7e1",slug:"cloud-computing-technology-and-practices",bookSignature:"Dinesh G. 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Limerick",institutionURL:null,country:{name:"Ireland"}}},{id:"259703",title:"Dr.",name:"Dinesh Babu",middleName:null,surname:"Duraibabu",fullName:"Dinesh Babu Duraibabu",slug:"dinesh-babu-duraibabu",email:"dineshbabu.duraibabu@ul.ie",position:null,institution:{name:"University of Limerick",institutionURL:null,country:{name:"Ireland"}}},{id:"269578",title:"Dr.",name:"Gabriel",middleName:null,surname:"Leen",fullName:"Gabriel Leen",slug:"gabriel-leen",email:"Gabriel.Leen@ul.ie",position:null,institution:null},{id:"269579",title:"M.Sc.",name:"Fintan",middleName:null,surname:"McGuinness",fullName:"Fintan McGuinness",slug:"fintan-mcguinness",email:"Fintan.McGuinness@ul.ie",position:null,institution:null},{id:"269580",title:"Dr.",name:"Gerard",middleName:null,surname:"Dooly",fullName:"Gerard Dooly",slug:"gerard-dooly",email:"Gerard.Dooly@ul.ie",position:null,institution:null}]},book:{id:"8271",title:"Applications of Optical Fibers for Sensing",subtitle:null,fullTitle:"Applications of Optical 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\r\n\tThe objective of this book is to make the food professionals acquainted with recent directions of the research work in food science. The different sections of this book project will describe the utilization of digital transformation in the food industry using the available applications of digital tools such as the internet of things (IoT), artificial intelligence (AI), sensor technologies, and blockchain. The effect of climate changes on the agro-industry will be discussed through the issues of climate changes, climate adaptation, agro-ecosystems, and environmental aspects and impacts. Recently, the food industry is subjected to unexpected new risks such as pandemics, lack of specific food supply, financial situations, and information technology problems so this too should be taken into consideration in the food science research work. As the food industry is a consumer-driven industry the continual improvement is a cornerstone in this industry. Recent technologies such as nanotechnology, membrane technology, and high-pressure technology besides the advanced analytical methods such as applications of the electron microscope and PCR would be covered.
",isbn:"978-1-80356-066-3",printIsbn:"978-1-80356-065-6",pdfIsbn:"978-1-80356-067-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"086633aee9a7b3ec134fb3a465418eac",bookSignature:"Prof. Yehia El-Samragy",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11741.jpg",keywords:"Internet of Things, Artificial Intelligence, Blockchain, Climate Change, Agroecosystems, Pandemics, Information Technology Problems, Lack of Specific Food Supply, Nanotechnology, High-Pressure Technology, PCR, Membrane Technology",numberOfDownloads:54,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 2nd 2021",dateEndSecondStepPublish:"December 23rd 2021",dateEndThirdStepPublish:"February 28th 2022",dateEndFourthStepPublish:"May 19th 2022",dateEndFifthStepPublish:"July 18th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Professor Emeritus of Food Science, International Expert Trainer of Food Safety and Quality Management Systems, IRCA Lead Auditor/Tutor of QMS, and Food Safety, FSPCA Lead Instructor of PCQI and FSVP courses, registered Tutor of Highfield Food Safety and HACCP",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"81644",title:"Prof.",name:"Yehia",middleName:null,surname:"El-Samragy",slug:"yehia-el-samragy",fullName:"Yehia El-Samragy",profilePictureURL:"https://mts.intechopen.com/storage/users/81644/images/system/81644.jpg",biography:"Dr. El-Samragy has over four decades of a professional career bridged between academia and industry. He is Professor Emeritus of Food Science at Ain Sham University, Cairo, Egypt, and Visiting Research Professor at Cornell University, Ithaca, NY and Utah State University, Logan, UT, USA. He is an International Expert Trainer of Food Safety and Quality Management Systems. He worked as an Expert at some international organizations including FAO, UNIDO, UNDP, JECFA, ISO, USAID, ACDI-VOCA and DANIDA, in different projects of technology transfer, food standards, food product development, waste utilization, cleaner production, implementation of integrated management systems. He is IRCA Lead Auditor/Tutor of QMS, and Food Safety (HACCP & ISO/FSSC 22000) (IRCA Certificate # 01182132), and Lead Instructor, FSPCA Preventive Controls for Human Food Course (FSPCA Certificate # d16e213f) and FSPCA Foreign Supplier Verification Programs (FSPCA Certificate # d26bcf6b). 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In the traditional way of production, it is produced immediately after milking from raw milk in upland cottages. The cheese is curdled with rennet, fermented by native lactic acid bacteria (LAB) and ripened for 7–10 days. Then, it is usually sent to a cheese factory, where the next technology processes (including salting) take part resulting in the production of the final soft “Bryndza” cheese [1, 2].
\nAs coagulase-positive staphylococci are ubiquitous in milk, the control of
The growth of
As a pathogen,
In addition, some strains of
To date, 23 SEs and enterotoxin-like (SEls) types have been described based on their antigenicity. They have sequentially been assigned a letter of the alphabet in order of their discovery (SEA, SEB, ….., SElX) [10–12]. SEA and SEB were the first one SEs characterized by Casman and Bergdoll in 1959 and 1960. From the late 1990s, new toxins were discovered one after another by sequencing the entire genome of
SEs and SEls proteins are globular, single peptides with molecular weights ranging from 19 to 29 kDa [16, 19]. Their molecular composition is characterized by containing only two residues of half cystine and one or two residues of tryptophane [20]. They are rich in lysine, aspartic and glutamic acids and tyrosine. Most of them possess a cysteine loop required for proper conformation and which is probably involved in the emetic activity [21]. Overall, 15% of amino acid residues are entirely conserved in SEs and occurred in four stretches of primary sequence located either centrally or at the C-terminus [9].
\nAs it is seen in Table 1, all genes for SEs and SEls are located on mobile genetic elements, including plasmids, transposons, prophages,
Toxin | Molecular weight (kDa) | Emetic activity | Super-antigenic activity | gene | Genetic element | Accessory genetic element |
---|---|---|---|---|---|---|
SEA | 27.1 | + | + | prophage | ΦSa3ms; ΦSa3mw; Φ252B; ΦNM3; ΦMu50a | |
SEB | 28.4 | + | + | chromosome, SaPI, plasmid | pZA10; SaPI3 | |
SEC1-SEC3 | 27.5-27.6 | + | + | SaPI | SaPIn1; SaPIm1; SaPImw2; SaPIbov1 | |
SED | 26.9 | + | + | plasmid (pIB485) | pIB485-like | |
SEE | 26.4 | + | + | prophage | ΦSa | |
SEG | 27.0 | + | + | |||
SEH | 25.1 | + | + | transposon | MGEmw2/mssa476 | |
SEI | 24.9 | + | + | |||
SElJ | 28.6 | nd | + | plasmid (pIB485, pF5) | pIB485-like; pF5 | |
SElK | 25.3 | nd | + | SaPI | ΦSa3ms; ΦSa3mw; SaPI1; SaPI3; SaPIbov1; SaPI5 | |
SElL | 24.7 | - | + | SaPI | SaPIn1; SaPIm1; SaPImw2; SaPIbov1 | |
SElM | 24.8 | nd | + | |||
SElN | 26.1 | nd | + | |||
SElO | 26.8 | nd | + | |||
SElP | 26.7 | nd | + | prophage (Sa3n) | ΦN315; ΦMu3A | |
SElQ | 25.2 | - | + | SaPI | ΦSa3ms; ΦSa3mw; SaPI1; SaPI3; SaPI5 | |
SER | 27.0 | + | + | plasmid (pIB485, pF5) | pIB485-like; pF5 | |
SES | 26.2 | + | + | plasmid (pF5) | pF5 | |
SET | 22.6 | + | + | plasmid (pF5) | pF5 | |
SElU | 27.2 | nd | + | |||
SElV | 27.6 | nd | + | |||
SElW | 23.2 | nd | nd | chromosome | ||
SElX | 19.3 | nd | + | chromosome |
Distribution of superantigens (SAg) gene is strain dependent. As reported by Jin and Yamada [17], 80% of human isolates contain at least one of these genes, including 50% which contain the
Staphylococcal enterotoxins (SEs) and SE-like toxins (SEls) are the most notable virulence factors associated with
Besides superantigen activity, SEs (but not SEls) act also as a potent gastrointestinal toxins causing emesis. SEs can penetrate the epithelium, accumulate in the submucosa, enter the blood stream and circulate through the body allowing activation of local and systemic immune response by their interaction with antigen-presenting- and T-cells [16, 25]. SEA binds in submucosa to the submucosal mast cells or directly to neuron cells [10, 26]. The binding of SEA to an unidentified receptor expressed on the surface of these cells induces the degranulation, resulting in the release of 5-hydroxytryptamine (5-HT). This stimulates 5-HT receptor on adjacent vagal afferent nerves in the intestine resulting in depolarization of the vagal nerves and stimulation of the vomiting centre in the brain [10, 16]. The release of 5-HT can be direct after interaction of SEA with enterochromaffin cells or neurons or indirect through the release of pro-inflammatory molecules or free-radical formation [13, 26]. It appears that besides 5-HT, also the serotonin pathway is involved in emesis, since serotonin is an important signalling mediator in the gastrointestinal tract and can activate enteric neurons, stimulate muscle responses and enhance secretion [23]. Release of inflammatory mediators (histamine, leukotrienes and neuroenteric peptide substance P) is responsible for local damage of gastrointestinal tract. The most severe lesions appear in the stomach and the upper part of the small intestine. Due to the inhibition of water and electrolyte reabsorption in small intestine, diarrhoea may occur [16, 25]. The dose of SEs inducing emetic activity in monkeys after oral administration ranged from 5 to 600 μg/animal [10]. The minimal dose required for intoxication in human is 144 ± 50 ng/humans for SEA and 0.4 μg/humans for SEB. All the SEls that were tested induced emetic reaction in monkeys at a dose of 100 μg/kg [11].
\nAlthough emetic and superantigenic activities are two separate functions localized on separate domains of the proteins, there is a high correlation between these activities and in most cases a loss of superantigen activity results in loss of emetic activity as [11, 18]. However, the role of SEls in human food-poisoning outbreaks currently remains unclear [12].
Approximately 20–60% of humans are permanent or intermittent carriers of
For SEB and SEC, the amounts may exceed 100 μg/ml, compared with 1–10 μg/ml for SEA and SED. Some indications exists that low amounts of SEB are produced already in early exponential growth phase and it can appear in cultures as early as 4–6 h. However, SEA and SED are produced in foods under a wider range of pH, redox potential (
The
SEs are highly stable, resist most proteolytic enzymes (pepsin or trypsin) thus keeping their activity in the digestive tract after ingestion. They are also resisting chymotrypsin, rennin and papain. Based on the poor ability of proteolytic enzymes to affect the biological activity of SEs, it is not surprising that SE levels are unaffected by proteolytic or enteric bacteria. Lactic acid bacteria (LAB), however, do decrease SE concentrations. It could not be accounted for the addition of lactic acid alone, suggesting the involvement of specific enzymes of other metabolites. Alternatively, selective physical adsorption of toxin to LAB may have occurred during removal of cells to obtain supernatants from toxin assays [9].
\nSEs are in general produced in a temperature range of 10–46°C, with the optimum at 40–45°C. Their production is substantially reduced at 20–25°C and it is unlikely that they are produced at temperatures below 10°C [19, 33, 34]. They can resist both the process of milk pasteurization and sterilization of canned foods [20, 36]. The heat stability of SEs is not the same for all of them and depends on the food matrix and toxin concentration. It decreases in the order SEC>SEB>SEA and significantly reduces in acidic conditions [3].
\nThe thermal inactivation can generally be described by
The pH range allowing the production of SEs is limited in higher degree as the growth of a producing strain. Optimum enterotoxin production occurs at pH 6–7 and it is influenced by environmental conditions, carbon and nitrogen source and salt level [33]. Already pH 5.0 is generally considered as a lower limit pH value. The SEA is produced under a wider range of pH than SEB or SEC [19, 38]. SEB can be destroyed by pepsin digestion at pH 2 but it is resistant at higher pHs, which are normal conditions in the stomach after food ingestion [9].
A characteristic feature that distinguishes
With respect to enterotoxins production requirements, values of water activity for their production are mostly in the same range as for the growth of the producer. In food with decreased water activity and at aerobic conditions, the enterotoxins can be produced even if the
Many intrinsic and extrinsic factors affect not only the growth of food-borne microbial pathogens but also metabolism and production of toxins. As SEs are extremely heat-stable and cannot be inactivated by measures such as heating of food, it is crucial to prevent their formation by preventing
The growth of
Model equation/validation coefficients | |||||||
---|---|---|---|---|---|---|---|
% | % | RSS | RMSE | %SEP | |||
1.117 | 1.001 | 11.7 | 0.974 | 96.9 | 0.0038 | 0.0142 | 9.2 |
1.175 | 1.000 | 17.5 | 0.942 | 93.0 | 0.0121 | 0.0252 | 12.8 |
1.096 | 0.999 | 9.6 | 0.988 | 98.6 | 0.0782 | 0.0538 | 8.2 |
1.327 | 1.003 | 32.7 | 0.921 | 90.3 | 1.4436 | 0.2832 | 0.8 |
1.217 | 0.999 | 21.7 | 0.980 | 97.7 | 0.8456 | 0.1961 | 1.3 |
1.246 | 0.999 | 24.6 | 0.973 | 96.9 | 1.3102 | 0.2203 | 5.1 |
Result of validation of Gibson’s model describing the effect of water activity on specific growth rate and Davey’s model describing lag phase duration of
Growth dynamics of
Plots of natural logarithm of specific growth rate (2a;
In general, a decrease of water activity prolonged the lag-phase duration and slowed down growth rate, until the minimal water activity was reached. At 18°C and
It was also noticed that except for cases when
The range in which the SED was (full markers) or was not (empty markers) detected during the growth of
At 21°C, the SED was not produced as sooner as after 24 h of incubation and even not at almost optimal water activity value (
The most rapid SED production was naturally observed at 37°C. At the higher water activity values,
Further, the Gibson’s model secondary model Gibson et al. [51] was used to characterise the influence of water activity and temperature on the specific growth rate of S. aureus 14733. Growth of S. aureus 14733 in nutrient broth was positively determined with the increasing value of water activity, resulting in shortening of the lag phase duration and more intensive growth in exponential phase. The growth of S. aureus in dependence on water activity at 18, 21 and 37 °C can be characterised by equations summarised in
For the Gibson’s model, the discrepancy factors ranged from 9.6% to 17.5%, so the model can be considered as very consistent. This model can be also used for the determination of optimal water activity value at each temperature. So, the optimal growth of S. aureus 14733 in nutrient broth at 18 °C can be expected at aw = 0.994, at 21°C at aw = 0.980 and at 37°C at water activity value of 0.986. The prediction of lag phase duration would be estimated with 22-33 % error according to Davey’s model. Taking into account that 12-37% of the bound of reliability during cultivation methods is tolerable; these finding demonstrate that the duration of lag phase and also the growth rate of S.
With regard to the EU Commission Regulation 1441/2007 [53], the total
Mutual effect of water activity and temperature on the production of SED in nutrient broth in dependence to
Based on the results,
As it was mentioned above, the traditional artisanal production of “Bryndza” cheese includes fermentation in the presence of LAB, ripening at temperatures from 18 to 21°C and salting with 2–5% NaCl resulting in final soft cheese [1, 2]. In this context, the growth and the production of SED by
As it is shown in Figure 4, the combination of reduced pH value (to values 6.0 and 5.5) and water activity value (0.99 and 0.97) did not inhibit the growth dynamic of
Growth dynamics of
Taking into account the SED production by
pH | (+) log CFU/ml | |||
---|---|---|---|---|
18 | 6.0 | – | 0.221 | 5.8 (28 h) |
5.5 | – | 0.320 | 5.7 (42 h) | |
5.0 | – | 0.119 | 4.9 (42 h) | |
4.5 | – | −0.016 | – | |
6.0 | 0.99 | 0.246 | 5.5 (28 h) | |
6.0 | 0.97 | 0.239 | 4.9 (28 h) | |
5.5 | 0.99 | 0.364 | 5.4 (28 h) | |
5.5 | 0.97 | 0.216 | – | |
21 | 6.0 | – | 0.392 | 6.2 (22 h) |
5.5 | – | 0.375 | 6.3 (22 h) | |
5.0 | – | 0.306 | 6.1 (32 h) | |
4.5 | – | 0.007 | – | |
6.0 | 0.99 | 0.378 | 6.1 (22 h) | |
6.0 | 0.97 | 0.295 | 6.5 (32 h) | |
5.5 | 0.99 | 0.389 | 6.0 (22 h) | |
5.5 | 0.97 | 0.258 | 6.2 (32 h) | |
37 | 6.0 | – | 2.287 | 5.2 (4 h) |
5.5 | – | 2.057 | 3.9 (4 h) | |
5.0 | – | 1.064 | 3.3 (6 h) | |
4.5 | – | 0.039 | – | |
6.0 | 0.99 | 1.847 | 4.8 (4 h) | |
6.0 | 0.97 | 1.534 | 3.6 (4 h) | |
5.5 | 0.99 | 1.403 | 3.9 (4 h) | |
5.5 | 0.97 | 1.073 | 4.9 (6 h) |
Effect of pH value and water activity on the growth parameters and production of SED by
In the term of SEs production inhibition during cheese manufacture, a rapid decrease in pH value down to pH 5.0 as fast as possible within first 6 h of cheese production is strongly recommended. This was also emphasized by Delbes et al. [48]. They observed that the critical phase of exponential phase of staphylococci occurs mainly within the first 6 h and the rapid pH decrease within this phase significantly contributed to the inhibition of staphylococci in young cheese. Moreover, if pH exceeded 6.3 within the first 6 h, also the SEs production was detected in cell concentration higher than 5 log CFU/g.
\nWith regard to the study of Valihrach et al. [54], based on a total of 24 examinations of SED presence in the nutrient broth in dependence to mutual effect of water activity (
In dairy practise, the initial numbers of
Growth dynamics and pH value changes during co-cultivation of
During co-cultivation of
pHlag (h) | ||||||
---|---|---|---|---|---|---|
15 | 3.26 | 24.7 | 4.20 | 1.16 | 0.061 | 0.397 |
4.23 | 28.6 | 3.98 | 0.90 | 0.104 | 0.375 | |
18 | 3.32 | 25.7 | 5.48 | 1.56 | 0.226 | 0.500 |
4.30 | 19.0 | 4.32 | 1.09 | 0.135 | 0.447 | |
21 | 2.04 | 15.2 | 5.26 | 2.27 | 0.215 | 0.426 |
3.04 | 14.2 | 4.46 | 1.52 | 0.144 | 0.421 |
Growth parameters of
So, even pH and lactic acid play only a minor role in growth inhibition, we may suppose that the expression of genes responsible for SEs production may be influenced negatively. In addition, the
During co-cultivation of 14733 isolate with Fresco culture, the SED was produced only after reaching
Based on this study focusing on the effect of temperature, pH, water activity and initial numbers of lactic acid bacteria on the growth and the ability of
In terms of SEs production inhibition during cheese manufacture, a rapid decrease in pH value down to pH 5.0 as fast as possible within the first 6 h of cheese production is strongly recommended. The minimal starter culture addition needed for
Artisanal raw milk cheese production poses a few critical factors limiting its safety. With reference to the growth of
We thank MSc. Zuzana Sirotná, MPH, and her co-workers for the SED detection. The results of the research in this chapter were supported by the Slovak Research and Development Agency, project no. APVV-15-0006.
Multiple pregnancies occur in 1 to 3% of live births, with special attention in the obstetric sphere due to its peculiarities, as it increases the risk of practically all prenatal pathologies. It represents about 12% of cases of extreme prematurity (less than 32 weeks), 25% of newborns weighing less than 1500 g, and also increases the risk of death before the first year of life by seven times [1].
Prematurity is responsible for unfavorable outcomes of the newborn that can evolve with respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis. All of these conditions increase perinatal morbidity/mortality and are related to potentially serious illness in the newborn requiring care in neonatal intensive units.
Prematurity represents the largest cause of perinatal mortality in the world, being a major focus of attention in the main research in recent years. In a twin pregnancy, it is 3 to 4 times greater, representing 12% of preterm infants. Throughout the literature, it was understood that as the number of fetuses increases, the duration of pregnancy decreases; approximately 50% of twins are born before or at week 36 and 50% of triplets or from pregnancies with more than three fetuses, before 32 weeks; and the mean gestational age at birth for twins is 36 weeks, for triplets 32 to 33, and for quadruplets approximately 31 [2].
The causes that determine preterm labor in multiple pregnancies are multifactorial [1].
Due to these facts, a twin pregnancy is said to be of high risk, therefore, the obstetrician must be fully updated to conduct challenging prenatal care and allow the best possible results for the maternal-fetal binomial to be obtained.
Even with the improvement in the survival of preterm newborns, mainly resulting from neonatal intensive care. Preterm birth remains an important public health problem and a leading cause of perinatal mortality and severe short- and long-term morbidities (blindness, deafness, developmental delay and/or other neurological impairments).
The use of corticosteroids is one of the most important therapies used in prenatal care to improve the outcomes of mortality and morbidity in the newborn [3].
The use of corticosteroids in a single course is done in situations of risk for premature birth between 24 and 34 weeks, including multiple pregnancies, premature rupture of ovular membranes and can also be used in fetuses with the gestational age of 23 weeks, with eminence for delivery within 7 days [4].
Studies initiated by Liggins in 1969 analyzed the effect of steroids on the lungs of fetuses of sheep and found that there was a discrepancy in the lungs of full-term offspring compared to premature offspring. With this experience, several clinical trials were carried out on its effect [5].
The first structured review addressing the use of this drug in premature fetuses was published by Crowley et al. in 1990. Later, in 1995, the author published a meta-analysis review citing 15 randomized clinical trials carried out between 1972 and 1994 and concluded that corticosteroids reduce in approximately 50% the risk of respiratory distress syndrome in fetuses born prematurely, when birth occurs after 24 hours to 7 days of the first dose of the drug [5, 6].
It is a practice-based on scientific evidence adopted for 20 years, which aims to reduce the incidence of neonatal death, respiratory distress syndrome, intraventricular hemorrhage or necrotizing enterocolitis and contribute to the survival of extremely preterm infants, having effects such as: cardiovascular adaptation, increased blood pressure, improved renal function and improved skin keratinization [7, 8, 9, 10].
Corticosteroids, unlike other forms of steroids, are easily transported across the placenta. They act on the airways in various ways, such as fetal lung maturation through thinning of the alveolar septa and alveolar differentiation with type 2 pneumocyte induction, which stimulates the production of surfactants [11].
In the fetus, cortisol plays an important role in development as it promotes the maturation of major organs in late pregnancy, including the respiratory system, kidney, gastrointestinal tract and brain. Fetal adrenal cortisol levels increase dramatically in the last six weeks before term completion and play a crucial role in later stages of organogenesis [12, 13].
The most important fetal organ in terms of survival at birth is the lung, where glucocorticoids act in the mesenchymal tissue to reduce the distances from blood vessels to the airways to allow for proper gas exchange. Glucocorticoids, in addition to promoting the production of surfactants, mature the pulmonary mechanisms for the elimination of fluid from the lung’s airways at birth [12].
After birth, dexamethasone has important anti-inflammatory effects in the neonatal lung, including direct suppression of proinflammatory cytokine gene expression, inhibition of cytokine production in lymphocytes and macrophages, and leads to apoptotic cell death of lymphocytes to further promote immune suppression [14].
The use of corticosteroids provides benefits by improving short-term respiratory morbidity. Premature newborns, when they require care, usually need to be admitted to an intensive care unit, with good recovery in most cases.
Despite these benefits, the use of corticosteroids can cause harm, including neonatal hypoglycemia. It has been shown that antenatal betamethasone results in elevated betamethasone concentrations and decreased cord blood cortisol concentrations at birth, leading to fetal hypothalamic pituitary adrenal axis suppression, persisting for up to seven days after birth. This practice results in high levels of blood glucose and C-peptide at birth and consequent hypoglycemia in the early neonatal period, which although appearing to be self-limited, has been reported to be associated with poor neurological outcomes [15, 16].
Seckl et al. in experimental work with animals reported that there may be adverse consequences in prenatal exposure to excess corticosteroids, as well as being a trigger for some diseases in adult life, such as cardiovascular diseases (dyslipidemia and hypertension), type 2 diabetes and impaired glucose tolerance [17, 18, 19]. Clark et al. and Edwards et al. reported the same result in their studies. Kari et al. observed delay in neurological development in childhood, but with a small sample size (n = 82) [20, 21, 22, 23].
Based on scientific reviews to date, the use of steroids has become the mainstay of prophylactic treatment in fetuses at risk of premature birth in singletons. However, there are still some outstanding issues regarding the use of medication, such as the increase in the rate of stillbirths in women with hypertensive syndromes. In addition, its use in parturients diagnosed with premature rupture of ovular membranes may increase the risk of neonatal infection [24, 25].
There are still insufficient data on childhood follow-up in fetuses who received corticosteroids during intrauterine life. There are only two studies that have followed steroid-treated fetuses into adulthood and found no differences in intellectual impairment or school performance [22, 26, 27].
Prophylactic corticosteroids use in multiple-dose protocols has not shown benefit in respiratory distress syndrome, in addition to having adverse effects on fetuses. Therefore, betamethasone is administered intramuscularly, in a daily dose of 12 mg, for two consecutive days or dexamethasone intramuscularly four 6 mg doses every 12 hours, in just one cycle and, exceptionally, two cycles [4].
In dichorionic pregnancies the term is 38 weeks, in uncomplicated diamniotic monochorionic pregnancies it is 36 weeks and in monoamniotic it is 32 weeks. As the term in twins is earlier, there is a greater risk of perinatal morbidity and mortality, especially in monochorionic, because the delivery is in late prematurity [28].
Routine use of corticosteroids in the twin is not recommended except in risky conditions for discontinuation before 34 weeks. There is still doubt in the literature regarding the dose, since the pharmacokinetics after administration of corticosteroids in twins is different in single pregnancies, as the recommended dose is the same for both [29]. Because of this, despite the short-term benefit, many questions remain unanswered in this population: such as the long-term effect of the drug, its pharmacokinetics, its real involvement in neurodevelopment and future metabolic consequences.
In the study by Hashimoto et al., evaluated in their retrospective cohort study consisting of 652 premature twins and 1705 premature single fetuses who were born weighing 500 to 1500 g (from 1991 to 1999), they concluded that the effect of corticosteroids in the prevention of neonatal mortality in twin pregnancies is similar to that observed in single pregnancies [30].
Blickstein and colleagues reported that a complete course of corticosteroids significantly reduced the incidence of respiratory distress syndrome in single children as well as in twins and triplets [31].
Melamed et al. administered a complete course of corticosteroids during prenatal care to twin pregnancies with a gestational age between 24 weeks to 33 weeks and 6 days. The outcome was a 58% reduction in neonatal mortality, decreased respiratory morbidity and severe neurological damage. The same results were observed in singleton pregnancies. The study was carried out in a tertiary neonatology center in Canada (Canadian Neonatal Network), from 2010 to 2014, with 9466 participants, consisting of 2516 mothers of twins and 6950 of singletons [32].
The effectiveness of the use of corticosteroids in multiple pregnancy was only approached retrospectively in 1996. Some difficulties were raised regarding its benefit in twin pregnancies with gestational age after 34 weeks in late prematurity [33, 34].
It has recently been biologically proven that administration of corticosteroids after 34 weeks of gestation reduces respiratory morbidity rates up to 72 hours after birth [33].
Three randomized clinical trials were published by Feitosa et al., Kamath et al. and Ramadam et al. confirming the beneficial effect in reducing transient tachypnea in newborns who used the full cycle of steroids during single gestation in late prematurity [35, 36, 37].
In 2016, a large randomized double-blind multicenter trial called Antenatal Betamethasone for Woman at Risk for Late Preterm Delivery (APLS) was published. Seventeen universities from the Eunice National Institute for Child and Human Development (NICHD) Fetal Medicine Units Network in Kennedy Shriver were included. Participants were assigned to receive two injections of betamethasone 12 mg in 24 hours.
A total of 2827 pregnant women with a gestational age of 34 weeks to 36 weeks +5 days were eligible, totaling 1427 women in the betamethasone group and 1400 in the placebo group. It resulted in significantly lower rates of severe respiratory complications in the betamethasone group compared to the placebo group (8.1% and 12.1%) and rates of various disorders were significantly lower in the betamethasone group than in the placebo group, they are: transient newborn tachypnea (6.7% and 9.9%), bronchopulmonary dysplasia (0.1% and 0.6%), transient newborn tachypnea or apnea (13.9% and 17.8%), resuscitation at birth (14.5% and 18.7%) and use of surfactant (1.8% and 3.1%). Apnea and pneumonia rates were similar in both groups [38].
The administration of corticosteroids beyond 34 weeks’ gestation has been the subject of many discussions around the world, as they are also at risk of significant morbidities, with an emphasis on respiratory morbidity.
However, there is no international consensus regarding the use of corticosteroids above 34 weeks due to the scarcity of trials and meta-analyses, as the long-term effects are still unknown.
Premature birth is increasing in most developed and developing countries. Overall, preterm birth is the leading cause of perinatal mortality and cerebral palsy remains one of the main long-term morbidities associated with preterm birth.
Cerebral palsy (CP) is the most common neurological impairment related to prematurity. The CP rate is closely linked to the prematurity rate; the more premature, the greater the risk of CP. The incidence of cerebral palsy is 14.6% between 22 and 27 weeks’ gestation, 6.2% between 28 and 31 weeks’ gestation, 0.7% between 32 and 36 weeks’ gestation, and 0.1% at the term of pregnancy [39].
Due to its association with preterm birth, multiple pregnancies also contribute to an increased risk of cerebral palsy, which increases 8-fold in double pregnancy and 47-fold in triple pregnancy [40].
It is a complex disease characterized by motor and/or postural dysfunction, has a permanent and non-progressive character, and can be recognized in the early stages of life. The four main types of cerebral palsy are spastic (increased muscle tone), dyskinetic (uncontrolled or slow movements), ataxic (difficulties with balance and depth perception), and mixed. Most cases of cerebral palsy (85–90%) are congenital and the most common type is spastic, which affects approximately 80% of individuals affected by the disease [41].
As there is no cure for cerebral palsy, among the various drugs used in an attempt to protect premature newborns from neurological complications, magnesium sulfate (MgSO4) has been the subject of a growing number of studies over the last decade.
The history of MgSO4 for neuroprotection began with the observation that the CP rate in pre-eclampsia was markedly lower compared to the gestational age in normotensive pregnancies and the subsequent decrease in neonatal neurological morbidity rates was initially suggested by some observational studies of the decade of 1990. The results of these studies supported the publication of systematic reviews and, also, opinion articles and guidelines by respected international scientific entities. Despite several large studies, with mostly positive results, the debate about routine MgSO4 continues, not only about dosage and administration, but also about safety aspects [42].
There are three large studies: ACTOMgSO4 (2003), PREMAG (2007) and BEAM (2008) that agreed that prenatal use of MgSO4 reduces the rate of cerebral palsy in newborns.
In 2003, Crowther et al. published the results of the ACTOMgSO4 study. A total of 1062 Australian and New Zealand women (1255 children) with less than 30 weeks’ gestation and expected to give birth within 24 hours were randomized. The initial dose of MgSO4 was 4 g IV in 20 minutes, followed by 1 g/hour IV for a maximum of 24 hours. As a conclusion of the study, the administration of MgSO4 before preterm delivery improved important pediatric outcomes without causing serious adverse effects [43].
In the work carried out by Marret et al. (PREMAG (2007)), 573 French women (688 children) with less than 33 weeks of pregnancy and with expected or planned delivery within 24 hours were included. A single IV dose of MgSO4 (4 g) or placebo was administered in 30 minutes. The main outcome of the study was to assess the existence of damage to the newborn’s cerebral white matter, whose diagnosis was made by cranial ultrasonography in the neonatal period. Data on the follow-up of surviving children up to two years of corrected age were described. That without statistical significance, there was protection against the combined outcome of cerebral palsy or death with the use of MgSO4 (RR 0.65; 95%CI 0.42–1.03) [44].
No serious maternal complications were observed in the group treated with MgSO4. Finally, the multicenter study BEAM (2008) had as sample number 2241 American pregnant women (2444 children) with imminent risk of delivery between 24 and 31 weeks. Pregnant women were randomly assigned to receive MgSO4 (6 g IV followed by a 2 g/h infusion) or placebo. MgSO4 administration was interrupted in cases where delivery did not occur within 12 hours. The primary outcome was the combination of fetal death or infant death with one year of corrected age or the presence of moderate/severe cerebral palsy with two years or more of corrected age. There was no significant difference between the primary outcomes of the MgSO4 and placebo groups (11.3 versus 11.7%; RR 0.97; 95%CI 0.77–1.23). However, in a pre-specified secondary analysis, the rate of moderate/severe cerebral palsy was significantly lower in the MgSO4 group (1.9 versus 3.5%; RR 0.55; 95% CI 0.32–0.95) [45].
Despite MgSO4’s role in preventing CP, many physicians are still concerned about side effects for both mother and baby. Since this mode of prevention is inexpensive, easy to use, and can reduce the rate of cerebral palsy by up to almost 50% [45].
Most guidelines (RCOG and Australian) recommend the administration of MgSO4 for fetal neuroprotection of viability for less than 30 weeks. Only SOGC has an upper cutoff at 32 weeks [46, 47, 48].
The definitive mechanism of action of the use of magnesium sulfate in fetal neuroprotection remains unclear. Biochemical and histopathological findings have been implicated as a possible mechanism to explain the neuroprotective effects of MgSO4 and these mechanisms include: neuroprotective ability to prevent early apoptosis of abnormal neuronal cells, decreased neuroinflammation to increase the seizure threshold, decreased hemorrhage of the cerebellum, stimulation of local adaptation responses through vasodilation and stimulation of neurogenesis in the premature maturation of brain cells by encouraging the secretion of neurotrophic factors [49, 50].
The developing brain (in preterm fetuses) is unconditionally vulnerable to insult and its response to adapt to a hypoxic condition is much lower compared to the brain in term fetuses. Damage to the fetal brain primarily occurs in the periventricular region, so it is often called periventricular leukomalacia, and lesions in this area can lead to clinical manifestations of cerebral palsy [50, 51, 52].
Until now, most maintenance doses have been advocated at 1 g/h. However, some studies suggest that if the objective were to optimize results, the dose would potentially have to be increased to a maintenance dose of 2 g/h. At this dose, the maximum dose to be administered is 64 g as shown by statistical simulation by Brookfield et al. However, other researchers claim that a maximum dose to avoid harmful effects would be 50 g [44, 53, 54].
Prenatal MgSO4-related maternal adverse events are widely researched. Common minor side effects include flushing, headache, heat and sweating, nausea, vomiting, blurred vision, or intramuscular discomfort at the injection site. Major adverse events can progress to respiratory and cardiac arrest and even death [55].
Several recent publications have confirmed the efficacy and safety (4 g loading dose, 1 g/h maintenance) of prenatal MgSO4 for preventing cerebral palsy, and this is considered an effective dose without compromising safety [56]. Other neuroprotective agents such as melatonin are being actively researched.
Twin pregnancy is an important cause of prematurity. To reduce perinatal morbidity/mortality, antenatal corticosteroids are used. Between 24 and 34 weeks the use of betamethasone in a dose of 12 mg intramuscularly two doses with an interval of 24 hours or dexametasone 6 mg intramuscularly 4 doses every 12 hours. It should be restricted to one or at most two cycles of corticosteroids.
The use of steroids in late prematurity in twin pregnancy is still controversial, however, several guidelines have suggested the use of steroids in elective preterm births such as in monochorionic pregnancies.
In addition to steroids, the use of magnesium sulfate protects the newborn from cerebral palsy.
Prenatal care for a twin pregnancy is challenging and the obstetrician must be aware of the use of corticosteroids and magnesium sulfate in cases of prematurity to reduce perinatal morbidity/mortality.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. 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She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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